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Radcliffe C, Kotton CN. Vaccination strategies for solid organ transplant candidates and recipients: insights and recommendations. Expert Rev Vaccines 2025; 24:313-323. [PMID: 40184037 DOI: 10.1080/14760584.2025.2489659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2024] [Revised: 03/04/2025] [Accepted: 04/02/2025] [Indexed: 04/05/2025]
Abstract
INTRODUCTION Vaccines save lives. They are integral to reducing the morbidity and mortality of vaccine-preventable infections in solid organ transplant recipients. Pre-transplant vaccination provides a unique opportunity for administration of live, viral vaccines, and enhanced vaccine efficacy, compared to the post-transplant period with decreased vaccine response due to immunosuppression. AREAS COVERED We discuss a general approach to pre- and post-transplant vaccination in solid organ transplant candidates and recipients. We then review guideline statements and recent literature related to individual vaccines, including the recently developed respiratory syncytial virus vaccine. Travel and occupation-related vaccines are also discussed. EXPERT OPINION The challenge of vaccination for immunocompromised patients expands as the prevalence of immunocompromised adults rises, and immunocompromised patients are frequently excluded from vaccine trials. In an age of vaccine hesitancy and reemerging vaccine-preventable infections, well-powered, prospective studies are needed to evaluate the clinical effectiveness of vaccines in solid organ transplant candidates and recipients.
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Affiliation(s)
| | - Camille N Kotton
- Transplant Infectious Disease and Compromised Host Program, Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA
- Travelers' Advice and Immunization Center, Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA
- Department of Medicine, Harvard Medical School, Boston, MA, USA
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2
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Santos AH, Belal A, Mehta R, Ibrahim H, Leghrouz MA, Alquadan K. Identification of non-virologic risk factors for lymphoma after the first year of kidney transplant in adults: A retrospective analysis. Cancer Epidemiol 2025; 97:102832. [PMID: 40344959 DOI: 10.1016/j.canep.2025.102832] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2025] [Revised: 04/20/2025] [Accepted: 04/26/2025] [Indexed: 05/11/2025]
Abstract
BACKGROUND Non-virologic risk factors for lymphoma after the first kidney transplant (KT) year or late-onset post-transplant lymphoma (PTL) have been scarcely studied. METHODS This secondary study re-analyzed de-identified, non-coded data. Cause-specific Cox regressions analyzed associations between non-virologic risk factors and lymphoma or all-cause mortality among kidney transplant recipients (KTRs) with conditional cancer-free survival one year after KT. RESULTS Among 166,256 adult KTRs, factors with the strongest risks for late-onset PTL were recipient age > /= 65 and 50-64 years (HR = 2.38, 95 % CI = 2.25-2.77, HR = 1.77, 95 % CI= 1.58-1.79; respectively) and pretransplant cancer history (HR = 1.46, 95 % CI = 1.21-1.77). Other risk factors for late-onset PTL included alemtuzumab induction, other primary kidney disease, a prior KT, male KTR sex, expanded criteria (ECD) transplant, and acute rejection. Factors associated with a decreased risk of late-onset PTL, albeit with an increased mortality risk, included native diabetic renal disease, pre-transplant dialysis > 2 years, and steroids or proliferation signal inhibitors maintenance immunosuppressant. CONCLUSION Non-virologic risk factors including KTRs advanced age or male sex, prior cancer or KT, alemtuzumab induction, ECD transplant, and acute rejection are associated with PTL beyond the first post-KT year.
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Affiliation(s)
- Alfonso H Santos
- College of Medicine, University of Florida, Gainesville, FL, USA.
| | - Amer Belal
- College of Medicine, University of Florida, Gainesville, FL, USA
| | - Rohan Mehta
- College of Medicine, University of Florida, Gainesville, FL, USA
| | - Hisham Ibrahim
- College of Medicine, University of Florida, Gainesville, FL, USA
| | | | - Kawther Alquadan
- College of Medicine, University of Florida, Gainesville, FL, USA
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Hansen CM, Bachmann S, Su M, Budde K, Choi M. Calcineurin Inhibitor Associated Nephrotoxicity in Kidney Transplantation-A Transplant Nephrologist's Perspective. Acta Physiol (Oxf) 2025; 241:e70047. [PMID: 40243357 PMCID: PMC12005075 DOI: 10.1111/apha.70047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Revised: 03/29/2025] [Accepted: 03/29/2025] [Indexed: 04/18/2025]
Abstract
AIM Calcineurin inhibitors (CNIs) have revolutionized transplant medicine, improving allograft survival but posing challenges like calcineurin inhibitor-induced nephrotoxicity (CNT). Acute CNT, often dose-dependent, leads to vasoconstriction and acute kidney injury, with treatment focusing on CNI exposure reduction. Chronic CNT manifests as progressive allograft function decline, with challenges in distinguishing it from nonspecific allograft nephropathy. METHODS This narrative review provides a concise overview of the clinical management of CNT, covering acute and chronic CNT. We reviewed original articles, landmark papers, and meta-analyses on CNT mitigation strategies, including CNI-sparing approaches. RESULTS Preventive measures include co-medications, CNI exposure monitoring, and CNI sparing strategies, such as reducing target trough levels and converting to mTOR inhibitors (mTORi) or belatacept. Despite improvements in graft function, challenges persist in demonstrating significant differences in allograft survival with CNI-sparing regimens. The paradigm shift from chronic CNT as the main cause of chronic allograft nephropathy toward rather immunologic triggered injuries and/or comorbidities as relevant contributors to allograft deterioration over time must be kept in mind. CONCLUSION CNIs have significantly improved kidney transplant outcomes, but their associated nephrotoxicity necessitates mitigation strategies. The decision to implement such regimens is always an individual choice balancing against the risk of immunologic injuries. Further long-term studies are needed to optimize immunosuppressive approaches and refine CNT management.
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Affiliation(s)
- Carla M. Hansen
- Department of Nephrology and Medical Intensive CareCharité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität Zu BerlinBerlinGermany
| | - Sebastian Bachmann
- Department of Nephrology and Medical Intensive CareCharité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität Zu BerlinBerlinGermany
| | - Mingzhen Su
- Department of Nephrology and Medical Intensive CareCharité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität Zu BerlinBerlinGermany
| | - Klemens Budde
- Department of Nephrology and Medical Intensive CareCharité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität Zu BerlinBerlinGermany
| | - Mira Choi
- Department of Nephrology and Medical Intensive CareCharité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität Zu BerlinBerlinGermany
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Kwon OJ, Aguayo E, Hadaya J, Tabibian K, Yalzadeh D, Gandjian M, Sanaiha Y, Zinoviev R, Benharash P. Association of Coronary Revascularization Modality and Timing With Outcomes of Acute Coronary Syndrome in Kidney Transplant Recipients. Am J Cardiol 2025; 242:53-60. [PMID: 39909324 DOI: 10.1016/j.amjcard.2025.01.029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2024] [Revised: 01/25/2025] [Accepted: 01/27/2025] [Indexed: 02/07/2025]
Abstract
Coronary artery disease (CAD) remains a leading cause of morbidity and mortality among renal transplant (RTx) recipients, with non-ST-segment-elevation acute coronary syndrome (NSTE-ACS) representing a disproportionately high burden. However, the optimal revascularization strategy for NSTE-ACS in RTx recipients remains unclear. This retrospective study analyzed the 2016 to 2021 Nationwide Readmissions Database. RTx recipients (≥18 years) undergoing coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) for NSTE-ACS were included. The primary outcome was in-hospital mortality, while perioperative complications, unplanned 30- and 90-day readmissions, repeat revascularization, and renal allograft failure were also considered. Multivariable logistic regression and Royston-Parmar models were used to identify the risk-adjusted association of revascularization modality, timing, and outcomes. Of an estimated 3,323 patients, 20.5% underwent CABG and 79.5% PCI. Following adjustment, CABG was associated with higher perioperative complications (AOR 3.46, 95% CI 2.31 to 5.19) and demonstrated a trend toward increased mortality risk (AOR 1.79, 95% CI 0.76 to 4.18). Royston-Parmar analysis demonstrated no difference in freedom from readmission or renal allograft failure within 90 days of discharge, but CABG was associated with a lower hazard of repeat revascularization (HR 0.24, 95% CI 0.08 to 0.76). Timing analysis revealed stable mortality rates across intervals for both modalities. While PCI complications increased with longer delays to revascularization, CABG demonstrated a more stable pattern. In conclusion, our findings suggest that PCI appears to be associated with lower risks of mortality and complications compared to CABG in RTx recipients with NSTE-ACS. However, CABG may offer benefits of reduced risk of repeat revascularization and greater flexibility in timing without compromising renal allograft function.
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Affiliation(s)
- Oh Jin Kwon
- Cardiovascular Outcomes Research Laboratories (CORELAB), David Geffen School of Medicine at University of California, Los Angeles, California; Center for Advanced Surgical and Interventional Technology, Department of Surgery, University of California, Los Angeles, California
| | - Esteban Aguayo
- Cardiovascular Outcomes Research Laboratories (CORELAB), David Geffen School of Medicine at University of California, Los Angeles, California; Center for Advanced Surgical and Interventional Technology, Department of Surgery, University of California, Los Angeles, California; Department of Surgery, Harbor-UCLA Medical Center, Torrance, California
| | - Joseph Hadaya
- Cardiovascular Outcomes Research Laboratories (CORELAB), David Geffen School of Medicine at University of California, Los Angeles, California; Center for Advanced Surgical and Interventional Technology, Department of Surgery, University of California, Los Angeles, California; Department of Surgery, David Geffen School of Medicine at University of California, Los Angeles, California
| | - Kevin Tabibian
- Cardiovascular Outcomes Research Laboratories (CORELAB), David Geffen School of Medicine at University of California, Los Angeles, California; Center for Advanced Surgical and Interventional Technology, Department of Surgery, University of California, Los Angeles, California
| | - Dariush Yalzadeh
- Cardiovascular Outcomes Research Laboratories (CORELAB), David Geffen School of Medicine at University of California, Los Angeles, California; Center for Advanced Surgical and Interventional Technology, Department of Surgery, University of California, Los Angeles, California
| | - Matthew Gandjian
- Cardiovascular Outcomes Research Laboratories (CORELAB), David Geffen School of Medicine at University of California, Los Angeles, California; Center for Advanced Surgical and Interventional Technology, Department of Surgery, University of California, Los Angeles, California; Division of Cardiac Surgery, Department of Surgery, David Geffen School of Medicine at University of California, Los Angeles, California
| | - Yas Sanaiha
- Cardiovascular Outcomes Research Laboratories (CORELAB), David Geffen School of Medicine at University of California, Los Angeles, California; Center for Advanced Surgical and Interventional Technology, Department of Surgery, University of California, Los Angeles, California; Department of Surgery, David Geffen School of Medicine at University of California, Los Angeles, California; Division of Cardiac Surgery, Department of Surgery, David Geffen School of Medicine at University of California, Los Angeles, California
| | - Radoslav Zinoviev
- Division of Cardiology, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, California
| | - Peyman Benharash
- Cardiovascular Outcomes Research Laboratories (CORELAB), David Geffen School of Medicine at University of California, Los Angeles, California; Center for Advanced Surgical and Interventional Technology, Department of Surgery, University of California, Los Angeles, California; Department of Surgery, David Geffen School of Medicine at University of California, Los Angeles, California; Division of Cardiac Surgery, Department of Surgery, David Geffen School of Medicine at University of California, Los Angeles, California.
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5
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Vinson AJ, Matas A. Late Allograft Loss and Contemporary Cardiorenal Metabolic Therapies. J Am Soc Nephrol 2025:00001751-990000000-00615. [PMID: 40193211 DOI: 10.1681/asn.0000000726] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/13/2025] Open
Abstract
Late kidney allograft loss occurs through one of two mechanisms: ( 1 ) deterioration of kidney function leading to retransplantation or dialysis (death-censored graft loss) and ( 2 ) premature death with a normally functioning transplant (death with graft function)-each accounting for approximately 50% of late kidney graft losses. Late death-censored graft loss typically results from a combination of immune and nonimmune events leading to common nonspecific end points ( e.g ., tubular atrophy, interstitial fibrosis, and glomerulosclerosis). Conversely, leading causes of death with graft function typically include cardiovascular events, malignancy, and infection. With an improved understanding of the multiple mechanism by which late graft dysfunction develops, there is an opportunity to identify patients at greatest risk and institute novel strategies to quell the process. Newer cardiometabolic agents with proven benefit in the general population have not been well-studied in kidney transplant recipients. However, in addition to their potential benefits in reducing cardiovascular, infectious, and malignancy end points (thus minimizing death with graft function risk), many novel agents may have additional anti-inflammatory and/or antifibrotic benefit (minimizing death-censored graft loss risk) in the kidney transplant population. In this review, we summarize existing literature regarding major causes of death-censored graft loss and death with graft function and discuss the potential roles of new cardiorenal metabolic agents including sodium-glucose cotransport 2 inhibitors, nonsteroidal mineralocorticoid receptor antagonists, glucagon-like peptide 1 receptor agonists, and dual endothelin and angiotensin receptor antagonists in the kidney transplant population, including potential mechanisms to improve death with graft function and death-censored graft loss outcomes.
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Affiliation(s)
- Amanda J Vinson
- Division of Nephrology, Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
- Kidney Research Institute of Nova Scotia
| | - Arthur Matas
- Department of Surgery, University of Minnesota, Minneapolis, Minnesota
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Mankowski MA, Bae S, Strauss AT, Lonze BE, Orandi BJ, Stewart D, Massie AB, McAdams-DeMarco MA, Oermann EK, Habal M, Iturrate E, Gentry SE, Segev DL, Axelrod D. Generalizability of kidney transplant data in electronic health records - The Epic Cosmos database vs the Scientific Registry of Transplant Recipients. Am J Transplant 2025; 25:744-755. [PMID: 39550008 PMCID: PMC11972892 DOI: 10.1016/j.ajt.2024.11.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Revised: 10/26/2024] [Accepted: 11/06/2024] [Indexed: 11/18/2024]
Abstract
Developing real-world evidence from electronic health records (EHR) is vital to advancing kidney transplantation (KT). We assessed the feasibility of studying KT using the Epic Cosmos aggregated EHR data set, which includes 274 million unique individuals cared for in 238 US health systems, by comparing it with the Scientific Registry of Transplant Recipients (SRTR). We identified 69 418 KT recipients who underwent transplants between January 2014 and December 2022 in Cosmos (39.4% of all US KT transplants during this period). The demographics and clinical characteristics of recipients captured in Cosmos were consistent with the overall SRTR cohort. Survival estimates were generally comparable, although there were some differences in long-term survival. At 7 years posttransplant, patient survival was 80.4% in Cosmos and 77.8% in SRTR. Multivariable Cox regression showed consistent associations between clinical factors and mortality in both cohorts, with minor discrepancies in the associations between death and both age and race. In summary, Cosmos provides a reliable platform for KT research, allowing EHR-level clinical granularity not available with either the transplant registry or health care claims. Consequently, Cosmos will enable novel analyses to improve our understanding of KT management on a national scale.
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Affiliation(s)
- Michal A Mankowski
- Department of Surgery, NYU Grossman School of Medicine, New York, New York, USA.
| | - Sunjae Bae
- Department of Surgery, NYU Grossman School of Medicine, New York, New York, USA; Department of Population Health, NYU Grossman School of Medicine, New York, New York, USA
| | - Alexandra T Strauss
- Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA
| | - Bonnie E Lonze
- Department of Surgery, NYU Grossman School of Medicine, New York, New York, USA
| | - Babak J Orandi
- Department of Surgery, NYU Grossman School of Medicine, New York, New York, USA; Center for Data Science, New York University, New York, New York, USA
| | - Darren Stewart
- Department of Surgery, NYU Grossman School of Medicine, New York, New York, USA
| | - Allan B Massie
- Department of Surgery, NYU Grossman School of Medicine, New York, New York, USA; Department of Population Health, NYU Grossman School of Medicine, New York, New York, USA
| | - Mara A McAdams-DeMarco
- Department of Surgery, NYU Grossman School of Medicine, New York, New York, USA; Department of Population Health, NYU Grossman School of Medicine, New York, New York, USA
| | - Eric K Oermann
- Center for Data Science, New York University, New York, New York, USA; Department of Neurosurgery, NYU Grossman School of Medicine, New York, New York, USA; Department of Radiology, NYU Langone Health, New York, New York, USA; Neuroscience Institute, NYU Langone Health, New York, New York, USA
| | - Marlena Habal
- Department of Medicine, NYU Grossman School of Medicine, New York, New York, USA
| | - Eduardo Iturrate
- Department of Medicine, NYU Grossman School of Medicine, New York, New York, USA
| | - Sommer E Gentry
- Department of Surgery, NYU Grossman School of Medicine, New York, New York, USA; Department of Population Health, NYU Grossman School of Medicine, New York, New York, USA
| | - Dorry L Segev
- Department of Surgery, NYU Grossman School of Medicine, New York, New York, USA; Department of Population Health, NYU Grossman School of Medicine, New York, New York, USA
| | - David Axelrod
- Department of Surgery, University Hospitals, Cleveland, Ohio, USA
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Beaudrey T, Bedo D, Weschler C, Caillard S, Florens N. From Risk Assessment to Management: Cardiovascular Complications in Pre- and Post-Kidney Transplant Recipients: A Narrative Review. Diagnostics (Basel) 2025; 15:802. [PMID: 40218153 PMCID: PMC11988545 DOI: 10.3390/diagnostics15070802] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2025] [Revised: 03/17/2025] [Accepted: 03/21/2025] [Indexed: 04/14/2025] Open
Abstract
Kidney transplantation remains the best treatment for chronic kidney failure, offering better outcomes and quality of life compared with dialysis. Cardiovascular disease (CVD) is a major cause of morbidity and mortality in kidney transplant recipients and is associated with decreased patient survival and worse graft outcomes. Post-transplant CVD results from a complex interaction between traditional cardiovascular risk factors, such as hypertension and diabetes, and risk factors specific to kidney transplant recipients including chronic kidney disease, immunosuppressive drugs, or vascular access. An accurate assessment of cardiovascular risk is now needed to optimize the management of cardiovascular comorbidities through the detection of risk factors and the screening of hidden pretransplant coronary artery disease. Promising new strategies are emerging, such as GLP-1 receptor agonists and SGLT2 inhibitors, with a high potential to mitigate cardiovascular complications, although further research is needed to determine their role in kidney transplant recipients. Despite this progress, a significant gap remains in understanding the optimal management of post-transplant CVD, especially coronary artery disease, stroke, and peripheral artery disease. Addressing these challenges is essential to improve the short- and long-term outcomes in kidney transplant recipients. This narrative review aims to provide a comprehensive overview of cardiovascular risk assessment and post-transplant CVD management.
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Affiliation(s)
- Thomas Beaudrey
- Nephrology Department, Hôpitaux Universitaires de Strasbourg, 67000 Strasbourg, France; (T.B.); (D.B.); (C.W.); (S.C.)
- Inserm UMR_S 1109 Immuno-Rhumatology Laboratory, Translational Medicine Federation of Strasbourg (FMTS), FHU Target, Faculté de Médecine, Université de Strasbourg, 67000 Strasbourg, France
| | - Dimitri Bedo
- Nephrology Department, Hôpitaux Universitaires de Strasbourg, 67000 Strasbourg, France; (T.B.); (D.B.); (C.W.); (S.C.)
- Inserm UMR_S 1109 Immuno-Rhumatology Laboratory, Translational Medicine Federation of Strasbourg (FMTS), FHU Target, Faculté de Médecine, Université de Strasbourg, 67000 Strasbourg, France
| | - Célia Weschler
- Nephrology Department, Hôpitaux Universitaires de Strasbourg, 67000 Strasbourg, France; (T.B.); (D.B.); (C.W.); (S.C.)
| | - Sophie Caillard
- Nephrology Department, Hôpitaux Universitaires de Strasbourg, 67000 Strasbourg, France; (T.B.); (D.B.); (C.W.); (S.C.)
- Inserm UMR_S 1109 Immuno-Rhumatology Laboratory, Translational Medicine Federation of Strasbourg (FMTS), FHU Target, Faculté de Médecine, Université de Strasbourg, 67000 Strasbourg, France
| | - Nans Florens
- Nephrology Department, Hôpitaux Universitaires de Strasbourg, 67000 Strasbourg, France; (T.B.); (D.B.); (C.W.); (S.C.)
- Inserm UMR_S 1109 Immuno-Rhumatology Laboratory, Translational Medicine Federation of Strasbourg (FMTS), FHU Target, Faculté de Médecine, Université de Strasbourg, 67000 Strasbourg, France
- INI-CRCT (Cardiovascular and Renal Trialists), F-CRIN Network, 67000 Strasbourg, France
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Prabhahar A, Batta A, Hatwal J, Kumar V, Ramachandran R, Batta A. Endothelial dysfunction in the kidney transplant population: Current evidence and management strategies. World J Transplant 2025; 15:97458. [PMID: 40104196 PMCID: PMC11612885 DOI: 10.5500/wjt.v15.i1.97458] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Revised: 09/04/2024] [Accepted: 11/04/2024] [Indexed: 11/26/2024] Open
Abstract
The endothelium modulates vascular homeostasis owing to a variety of vasoconstrictors and vasodilators. Endothelial dysfunction (ED), characterized by impaired vasodilation, inflammation, and thrombosis, triggers future cardiovascular (CV) diseases. Chronic kidney disease, a state of chronic inflammation caused by oxidative stress, metabolic abnormalities, infection, and uremic toxins damages the endothelium. ED is also associated with a decline in estimated glomerular filtration rate. After kidney transplantation, endothelial functions undergo immediate but partial restoration, promising graft longevity and enhanced CV health. However, the anticipated CV outcomes do not happen due to various transplant-related and unrelated risk factors for ED, culminating in poor CV health and graft survival. ED in kidney transplant recipients is an under-recognized and poorly studied entity. CV diseases are the leading cause of death among kidney transplant candidates with functioning grafts. ED contributes to the pathogenesis of many of the CV diseases. Various biomarkers and vasoreactivity tests are available to study endothelial functions. With an increasing number of transplants happening every year, and improved graft rejection rates due to the availability of effective immunosuppressants, the focus has now shifted to endothelial protection for the prevention, early recognition, and treatment of CV diseases.
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Affiliation(s)
- Arun Prabhahar
- Department of Telemedicine (Internal Medicine and Nephrology), Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Akshey Batta
- Department of Urology and Renal Transplant, Neelam Hospital, Rajpura 140401, Punjab, India
| | - Juniali Hatwal
- Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Vivek Kumar
- Department of Nephrology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Raja Ramachandran
- Department of Nephrology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Akash Batta
- Department of Cardiology, Dayanand Medical College and Hospital, Ludhiana 141001, Punjab, India
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Schwotzer N, Lu Y, Halfon M, Pascual M, Marques-Vidal P, Golshayan D, Wuerzner G. Prevalence of hypertension and uncontrolled hypertension after solid organ transplantation: a 5-year follow-up of the Swiss Transplant Cohort Study. J Hypertens 2025; 43:397-404. [PMID: 39445485 PMCID: PMC11789600 DOI: 10.1097/hjh.0000000000003905] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Revised: 09/10/2024] [Accepted: 09/28/2024] [Indexed: 10/25/2024]
Abstract
OBJECTIVE Hypertension (HTN) increases cardiovascular risk and is a frequent finding across all solid organ transplant recipients. We describe the prevalence of HTN and uncontrolled HTN, as well as details on pharmacologic treatment of HTN across solid organs transplant recipients up to five years after transplantation. METHODS This retrospective study is nested in the prospective Swiss Transplant Cohort Study ( www.stcs.ch ) that includes kidney, heart, lung, and liver transplantation. Data extraction from 2008 to 2019 was used for this study and follow-up data at 6, 12 and 60 months was analyzed. RESULTS A total of 3865 transplant recipients were included for analysis. The prevalence of HTN at 6 and 60 months was 88.9% and 90.4% in kidney ( P = 0.21), 61.8% and 76.1% in liver ( P < 0.01), 72.6% and 84.9% in lung ( P < 0.01), and 89.3% and 85.8% in heart ( P = 0.33) transplant recipients, respectively. The prevalence of uncontrolled HTN at 6 and 60 months was 40.3% and 38.9% in kidney ( P = 0.48), 21.2% and 30.5% in liver ( P = 0.05), 26.0% and 36.8% in lung ( P = 0.03) and 38.9% and 18.5% in heart ( P < 0.01) transplant recipients, respectively. At 12 months, compared to heart transplant recipients, kidney [odds ratio (OR) = 1.6, 95% confidence interval (CI) 1.1-2.1], liver (OR = 1.7, 95% CI 1.1-2.6) and lung (OR = 2.6, 95% CI 1.6-4.0) transplant recipients had a higher likelihood of presenting with uncontrolled HTN. CONCLUSION HTN prevalence after solid organ transplantation is high. Uncontrolled and untreated HTN remain a major issue post transplantation, particularly in organ recipients not necessarily suffering from cardiovascular diseases such as liver or lung transplant recipients.
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Affiliation(s)
| | - Yimin Lu
- Service of Nephrology and Hypertension
| | | | - Manuel Pascual
- Transplantation Center, Departments of Medicine and Surgery
| | - Pedro Marques-Vidal
- Department of Medicine, Internal Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Dela Golshayan
- Transplantation Center, Departments of Medicine and Surgery
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Lovatto V, Sousa BDS, Marães VRFDS. Is High-Intensity Interval Training an Option for Post-Kidney Transplant Physical Rehabilitation Programmes? A Scoping Review. J Multidiscip Healthc 2025; 18:1231-1239. [PMID: 40041241 PMCID: PMC11878123 DOI: 10.2147/jmdh.s491605] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Accepted: 12/18/2024] [Indexed: 03/06/2025] Open
Abstract
Purpose To systematically and broadly review the literature to show the available information on high-intensity interval training for kidney transplant recipients as an adjunct to physical rehabilitation. Methods A scoping review of high-intensity interval training for post-kidney transplant patients was conducted by searching the PubMed, EMBASE (Elsevier), Scopus (Elsevier), Web of Science, and PEDro databases. Full-text records on the subject were included. Articles not published in English were excluded. The selected articles went through careful production quality analysis using the PEDro scale. Results The search identified 26 articles, 3 of which met the inclusion criteria. The material demonstrated satisfaction, confidence, improvement in resting heart rate, and absence of adverse effects from high-intensity interval training for kidney transplant recipients. Conclusion Based on this scoping review, high-intensity interval training for kidney transplant patients may be beneficial for physical and mental aspects and complement physical rehabilitation programmes, but there is a need for more studies with robust samples and long-term follow-up to confirm these benefits.
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Affiliation(s)
- Viviane Lovatto
- Postgraduate Programme in Health Sciences and Technologies, University of Brasília, Ceilândia, Brazil
- Faculty of Physiotherapy, University of Rio Verde, Rio Verde, Brazil
| | - Bruna da Silva Sousa
- Postgraduate Programme in Health Sciences and Technologies, University of Brasília, Ceilândia, Brazil
| | - Vera Regina Fernandes da Silva Marães
- Postgraduate Programme in Health Sciences and Technologies, University of Brasília, Ceilândia, Brazil
- Postgraduate Programme in Biomedical Engineering, University of Brasilia, Gama, Brazil
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11
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Concannon K, Bentz Z, Kokosa S, Berry H, Byrns J. Evaluation of lipid management practices for secondary atherosclerotic cardiovascular disease prevention in abdominal solid organ transplant recipients. J Clin Lipidol 2025:S1933-2874(25)00023-6. [PMID: 40157862 DOI: 10.1016/j.jacl.2025.02.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2024] [Revised: 01/07/2025] [Accepted: 02/04/2025] [Indexed: 04/01/2025]
Abstract
BACKGROUND High-intensity HMG-CoA reductase inhibitors (statins) are recommended for secondary atherosclerotic cardiovascular disease (ASCVD) prevention. Solid organ transplant (SOT) recipients are at an increased risk of ASCVD events. This study evaluated if abdominal SOT recipients who experienced an ASCVD event prior to transplant received guideline-directed pharmacotherapy for secondary ASCVD prevention post-transplant. METHODS Single-center, retrospective, cohort study that evaluated lipid-lowering therapy prescribing practices in SOT recipients transplanted at Duke University Hospital. The primary objective was the percentage of patients receiving a high-intensity statin regimen during the first year post-transplant. Secondary objectives included reason for change in statin therapy, other lipid-lowering medications prescribed, percentage of patients who had lipid panel(s) drawn, safety of statin therapy, and the incidence of recurrent ASCVD or death secondary to an ASCVD event within the first year post-transplant. RESULTS Sixty-three transplant patients were included, 46 (73%) received a kidney, 12 (19%) a liver, and 5 (7.9%) a multi-organ transplant. Twenty-four patients (38.1%) were maintained on a high-intensity statin during the first year post-transplant. Reason for statin dose change included elevated lipids (35.3%), statin-related safety event (11.8%), and undocumented reason (52.9%). Statins were well tolerated. Two (3.2%) patients experienced a recurrent myocardial infarction within the first year post-transplant. CONCLUSION Less than half of the abdominal transplant patients were maintained on guideline-directed high-intensity statin therapy for secondary ASCVD prevention at 1 year post-transplant. Our findings demonstrate an opportunity to optimize the prescribing practices of lipid-lowering therapy following abdominal transplant in a high cardiovascular risk population.
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Affiliation(s)
- Kennedy Concannon
- Department of Pharmacy, University of Colorado Anschutz Medical Center, Aurora CO, USA (Dr Concannon)
| | - Zachary Bentz
- Department of Pharmacy, Carilion Clinic Roanoke Memorial Hospital, Roanoke VA, USA (Dr Bentz)
| | - Sarah Kokosa
- Department of Pharmacy, Duke University Hospital, Durham NC, USA (Drs Kokosa and Byrns)
| | - Holly Berry
- Department of Pharmacy, Durham Veterans Affairs Medical Center, Durham NC, USA (Dr Berry)
| | - Jennifer Byrns
- Department of Pharmacy, Duke University Hospital, Durham NC, USA (Drs Kokosa and Byrns).
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12
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Thu HNT, Thuy DNT, Vu TP, Quoc TP, Van DN, Do Manh H, Thi VD, Thi DT, Le Ha K, Quy KT, Trung KN, Le Viet T. Plasma high-sensitivity C-reactive protein measured prior to transplant is related to prediabetes in first-year kidney transplant recipients: A single-center cross-sectional study in Vietnam. Transpl Immunol 2025; 88:102149. [PMID: 39586333 DOI: 10.1016/j.trim.2024.102149] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Revised: 11/11/2024] [Accepted: 11/18/2024] [Indexed: 11/27/2024]
Abstract
AIM To determine the rate of prediabetes among and the pre-transplant plasma high-sensitivity C-reactive protein (hs-CRP) value predictive of prediabetes in patients during their first year post-living donor kidney transplant. METHODS A total of 538 patients underwent living donor kidney transplantation between January 2018 and December 2020, 413 of whom met the inclusion criteria for this study. All patients underwent oral glucose tolerance tests (OGTTs) with 75 g glucose/200 mL solution, starting 3 months post-transplant and repeating the test every 3 months for the first year. Clinical and paraclinical indicators and plasma hs-CRP concentrations were quantified the day prior to the transplant. Prediabetes was diagnosed according to the American Diabetes Association 2018 criteria as a 2-h OGTT result between 140 mg/dL (7.8 mmol/L) and 199 mg/dL (11.0 mmol/L). RESULTS The rate of prediabetes among the study subjects was 38.3 % (158/413). Body mass index (BMI) and pre-transplant plasma triglycerides, high-density lipoprotein cholesterol (HDLC), and hs-CRP levels were related factors predictive of prediabetes in patients within the first year post-kidney transplant based on multivariate logistic regression and receiver operative characteristic curve models. Hs-CRP was the factor with the best predictive value (area under the curve = 0.89; p < 0.001). CONCLUSIONS Pre-transplant plasma hs-CRP levels were a good predictor of prediabetes in the first year post-living donor kidney transplant.
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Affiliation(s)
- Ha Nguyen Thi Thu
- Military Hospital 103, Ha Noi, Viet Nam; Vietnam Military Medical University, Ha Noi, Viet Nam
| | - Dung Nguyen Thi Thuy
- Military Hospital 103, Ha Noi, Viet Nam; Vietnam Military Medical University, Ha Noi, Viet Nam
| | | | - Toan Pham Quoc
- Military Hospital 103, Ha Noi, Viet Nam; Vietnam Military Medical University, Ha Noi, Viet Nam
| | - Duc Nguyen Van
- Military Hospital 103, Ha Noi, Viet Nam; Vietnam Military Medical University, Ha Noi, Viet Nam
| | - Ha Do Manh
- Military Hospital 103, Ha Noi, Viet Nam; Vietnam Military Medical University, Ha Noi, Viet Nam
| | - Van Diem Thi
- Military Hospital 103, Ha Noi, Viet Nam; Vietnam Military Medical University, Ha Noi, Viet Nam
| | - Doan Tran Thi
- National Hospital of Endocrinology, Ha Noi, Viet Nam
| | - Khoa Le Ha
- Hanoi Medical University, Ha Noi, Viet Nam
| | | | - Kien Nguyen Trung
- Military Hospital 103, Ha Noi, Viet Nam; Vietnam Military Medical University, Ha Noi, Viet Nam
| | - Thang Le Viet
- Military Hospital 103, Ha Noi, Viet Nam; Vietnam Military Medical University, Ha Noi, Viet Nam.
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13
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Ubenauf TA, von der Born J, Sugianto RI, Grabitz C, Lehmann E, Memaran N, Kanzelmeyer N, Falk J, Babazade N, Sarikouch S, Renz DM, Schmidt BMW, Melk A. Elevated septal native T1 time in cardiac magnetic resonance imaging suggesting myocardial fibrosis in young kidney transplant recipients. J Cardiovasc Magn Reson 2025; 27:101839. [PMID: 39814266 PMCID: PMC11870264 DOI: 10.1016/j.jocmr.2025.101839] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Revised: 12/11/2024] [Accepted: 01/09/2025] [Indexed: 01/18/2025] Open
Abstract
BACKGROUND Patients after kidney transplantation (KTx) in childhood show a high prevalence of cardiac complications, but the underlying mechanism is still poorly understood. In adults, myocardial fibrosis detected in cardiovascular magnetic resonance (CMR) imaging is already an established risk factor. Data for children after KTx are not available. This study aimed to explore cardiac function and structure with focus on myocardial fibrosis and associated risk factors in KTx recipients. METHODS Forty-six KTx recipients (mean age 16.0 ± 3.5 years) and 46 age- and sex-matched healthy controls were examined with non-contrast CMR imaging. Native T1 time (nT1), a marker for myocardial fibrosis, was measured at the interventricular septum. Other parameters comprised left ventricular mass index (LVMI), left ventricular ejection fraction (LVEF), and global longitudinal strain (GLS). Multivariable linear regression analyses were used to explore associations with nT1. RESULTS Mean nT1 was significantly higher in KTx recipients compared to controls (1198.1 ± 48.8 vs 1154.4 ± 23.4 ms, p < 0.0001). 46% (21/46) had a nT1 above the upper limit of the normal range (mean + 2 standard deviations of controls). KTx recipients showed higher LVMI z-scores (0.1 ± 1.1 vs -0.3 ± 0.7, p = 0.026), higher LVEF (67.3 ± 3.8% vs 65.3 ± 3.6%, p = 0.012), and lower GLS (-19.0 ± 2.1% vs -20.3 ± 2.7%, p = 0.010). Higher systolic blood pressure (ß = 1.284, p = 0.001), LVMI (ß = 1.542, p < 0.001), and LVEF (ß = 3.535, p = 0.026) were associated with longer nT1 only in KTx recipients, but not in controls. Only 2 KTx recipients exhibited left ventricular hypertrophy; however, a total of 18 displayed elevated nT1 with LVMI z-score within the normal range. CONCLUSION Our data suggest the presence of cardiac remodeling with myocardial fibrosis in a significant proportion of young KTx recipients. Non-contrast CMR imaging has the potential to visualize early structural cardiac changes and could become an important diagnostic adjunct in the follow-up of KTx recipients. Longitudinal studies are needed to further evaluate the importance of nT1 in early identification of those at high risk for sudden cardiac death allowing to integrate preventive strategies.
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Affiliation(s)
- Tim Alexander Ubenauf
- Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
| | - Jeannine von der Born
- Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
| | - Rizky I Sugianto
- Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
| | - Carl Grabitz
- Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
| | - Elena Lehmann
- Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
| | - Nima Memaran
- Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
| | - Nele Kanzelmeyer
- Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
| | - Jan Falk
- Institute of Diagnostic and Interventional Radiology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
| | - Nigar Babazade
- Institute of Diagnostic and Interventional Radiology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
| | - Samir Sarikouch
- Department of Cardiothoracic, Transplantation and Vascular Surgery, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
| | - Diane Miriam Renz
- Institute of Diagnostic and Interventional Radiology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
| | | | - Anette Melk
- Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
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14
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Anwar IJ, DeLaura I, Ladowski JM, Schilirò D, Gao Q, Manook M, Yoon J, Belloni R, Park A, Schuster DJ, Song M, Lin L, Farris AB, Magnani D, Williams K, Kwun J, Knechtle SJ. CD154 blockade effectively controls antibody-mediated rejection in highly sensitized nonhuman primate kidney transplant recipients. Sci Transl Med 2025; 17:eadn8130. [PMID: 39742504 PMCID: PMC11797747 DOI: 10.1126/scitranslmed.adn8130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Accepted: 12/05/2024] [Indexed: 01/03/2025]
Abstract
Current desensitization and maintenance immunosuppression regimens for kidney transplantation in sensitized individuals show limited ability to control the posttransplant humoral response, resulting in high rates of antibody-mediated rejection (ABMR) and graft failure. Here, we showed that anti-CD154 monoclonal antibody (mAb)-based immunosuppression more effectively controlled allograft rejection and humoral rebound in a highly sensitized nonhuman primate kidney transplantation model compared with tacrolimus-based standard-of-care (SOC) immunosuppression. Desensitization with an anti-CD154 mAb (5C8) and a proteasome inhibitor led to decreased donor-specific antibodies (DSAs) and disruption of lymph node germinal centers with reduction of proliferating, memory, and class-switched B cells as well as T follicular helper cells. After transplant, the nonhuman primates maintained on 5C8-based immunosuppression had significantly better survival compared with those maintained on SOC immunosuppression (135.2 days versus 32.8 days, P = 0.013). The 5C8-treated group demonstrated better suppression of DSAs after transplant, more robust suppression of B cell populations, and better induction of regulatory T cells. Fewer infectious and welfare complications, including viral reactivation and weight loss, were also observed with 5C8-based immunosuppression compared with SOC immunosuppression. Therefore, anti-CD154 mAbs may improve kidney transplant outcomes through better control of posttransplant immune responses. The superior efficacy of anti-CD154 mAb-based immunosuppression over tacrolimus-based SOC seen in this highly sensitized NHP transplant model suggests that anti-CD154 mAbs could potentially be used to desensitize and treat highly sensitized patients receiving kidney transplantation.
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Affiliation(s)
- Imran J. Anwar
- Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
| | - Isabel DeLaura
- Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
| | - Joseph M. Ladowski
- Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
| | - Davide Schilirò
- Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
| | - Qimeng Gao
- Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
| | - Miriam Manook
- Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
| | - Janghoon Yoon
- Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
| | - Rafaela Belloni
- Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
| | - Angela Park
- Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
| | - Daniel J. Schuster
- Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
| | - Mingqing Song
- Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
| | - Lin Lin
- Department of Biostatistics & Bioinformatics, Duke University Medical Center, Durham, NC 27710, USA
| | - Alton B. Farris
- Department of Pathology, Emory University School of Medicine; Atlanta, GA 30322, USA
| | - Diogo Magnani
- Nonhuman Primate reagent Resource, UMass Chan Medical School, Worcester, MA 01605, USA
| | - Kyha Williams
- Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
| | - Jean Kwun
- Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
| | - Stuart J. Knechtle
- Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
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15
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Ebadinejad A, Silver E, O'Sullivan DM, Dar W, Morgan G, Emmanuel B, Cobar JP, Ye X, Singh JU, Kent R, Tremaglio J, Serrano OK. Outcomes in Patients With Henoch-Schönlein Purpura After Kidney Transplantation: A Propensity Score Matched Study. Nephrology (Carlton) 2025; 30:e14431. [PMID: 39821923 DOI: 10.1111/nep.14431] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Revised: 11/22/2024] [Accepted: 01/01/2025] [Indexed: 01/19/2025]
Abstract
AIM Henoch-Schönlein purpura (HSP) nephritis leads to end-stage renal disease (ESRD) in upto 3% of cases, necessitating kidney transplantation (KT). This study compared graft and patient survival outcomes between HSP and non-HSP KT recipients and identified factors associated with HSP recurrence. METHODS Data from the Scientific Registry of Transplant Recipients (SRTR) were analysed for adult and paediatric KT patients listed between January 2005 and April 2021. HSP recipients were extracted from the database and non-HSP recipients were selected and propensity-matched 3:1 based on demographic factors. RESULTS A total of 371 KT recipients with HSP were matched to 1113 non-HSP recipients. When stratified by age, adult and paediatric HSP patients showed similar death-censored graft survival (DCGS) at 5 years compared to their non-HSP counterparts. Furthermore, paediatric patients with HSP had comparable DCGS to adult HSP patients at 5 years (86.5% vs. 88.3%, p = 0.221). Amongst HSP recipients, 27.2% experienced recurrence, with higher rates in adults (29.7%) compared to children (13.0%). Recurrent HSP was associated with increased graft failure and mortality. Regression analysis showed that older age (OR [95% CI]: 1.018 (1.001-1.035), p = 0.037) was associated with a higher risk of recurrence, while a higher BMI (0.95 [0.91-0.99], p = 0.020) was linked to a lower risk. CONCLUSION In a contemporary cohort of HSP KT patients, graft survival was comparable between HSP and matched non-HSP patients in both adult and paediatric groups. However, graft loss was more frequent in HSP patients who experienced disease recurrence.
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Affiliation(s)
- Amir Ebadinejad
- Transplant & Comprehensive Liver Center, Hartford, Connecticut, USA
| | - Elizabeth Silver
- Department of Surgery, University of Connecticut School of Medicine, Farmington, Connecticut, USA
| | - David M O'Sullivan
- Department of Research Administration, Hartford HealthCare, Hartford, Connecticut, USA
| | - Wasim Dar
- Transplant & Comprehensive Liver Center, Hartford, Connecticut, USA
- Department of Surgery, University of Connecticut School of Medicine, Farmington, Connecticut, USA
| | - Glyn Morgan
- Transplant & Comprehensive Liver Center, Hartford, Connecticut, USA
- Department of Surgery, University of Connecticut School of Medicine, Farmington, Connecticut, USA
| | - Bishoy Emmanuel
- Transplant & Comprehensive Liver Center, Hartford, Connecticut, USA
- Department of Surgery, University of Connecticut School of Medicine, Farmington, Connecticut, USA
| | - Juan P Cobar
- Transplant & Comprehensive Liver Center, Hartford, Connecticut, USA
| | - Xiaoyi Ye
- Transplant & Comprehensive Liver Center, Hartford, Connecticut, USA
| | - Joseph U Singh
- Transplant & Comprehensive Liver Center, Hartford, Connecticut, USA
| | - Rebecca Kent
- Transplant & Comprehensive Liver Center, Hartford, Connecticut, USA
| | - Joseph Tremaglio
- Transplant & Comprehensive Liver Center, Hartford, Connecticut, USA
| | - Oscar K Serrano
- Transplant & Comprehensive Liver Center, Hartford, Connecticut, USA
- Department of Surgery, University of Connecticut School of Medicine, Farmington, Connecticut, USA
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16
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Dash K, Mishra M. The tradeoff between the efficacy of calcineurin inhibitors: prevention of allograft rejection vs. post-transplant renal and cardiovascular complications. Crit Rev Toxicol 2025; 55:63-79. [PMID: 39807635 DOI: 10.1080/10408444.2024.2433631] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Accepted: 11/19/2024] [Indexed: 01/16/2025]
Abstract
Solid organ transplantation has emerged as a crucial intervention in the field of medicine. During transplantation, our human body perceives the organ as an exogenous entity or graft, initiating an immune reaction to eliminate it. This immune response ultimately culminates in the rejection of the graft. So, to mitigate the possibility of graft rejection, implementing immune suppression is imperative. In this context, the utilization of calcineurin inhibitors (CNIs) assumes a pivotal role. Calcineurin inhibitors significantly preserve immunosuppression following solid organ transplantation. Calcineurin inhibitors have considerably improved short-term results in renal transplantation by reducing acute rejection rates. Concerning the limited therapeutic window of these medications, careful monitoring of pharmacological treatment and individual doses is required. However, a significant number of patients do experience CNI toxicity. Side effects of CNIs include renal failure, hypertension, respiratory disorders, gastrointestinal damage, gingivitis, and so on. Higher trough level of the drug causes acute nephrotoxicity, which is of three types: functional toxicity, tubular toxicity, and vascular toxicity. Acute nephrotoxicity, if untreated, leads to irreversible, progressive deterioration of allograft function, leading to chronic nephrotoxicity. Cardiovascular toxicity of CNIs includes atrial hypertension caused by vasoconstriction of the afferent arteriole, vascular remodeling, hypertrophy, dyslipidemia, and also the onset of diabetes. Such clinical complications further affect the patient's survivability and subjective well-being, possibly leading to graft loss. This review focuses on the most severe side effects of CNIs: renal and cardiovascular toxicity.
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Affiliation(s)
- Kalpanarani Dash
- Department of Life Sciences, Neural Developmental Biology Lab, National Institute of Technology, Rourkela, India
| | - Monalisa Mishra
- Department of Life Sciences, Neural Developmental Biology Lab, National Institute of Technology, Rourkela, India
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Ziaja J, Skrabaka D, Owczarek AJ, Widera M, Król R, Kolonko A, Więcek A. Long-Term Results of Kidney Transplantation in Patients Aged 60 Years and Older. J Clin Med 2024; 14:78. [PMID: 39797161 PMCID: PMC11722099 DOI: 10.3390/jcm14010078] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2024] [Revised: 12/17/2024] [Accepted: 12/24/2024] [Indexed: 01/13/2025] Open
Abstract
Background/Objectives: The results of kidney transplantation (KTx) in elderly patients are deteriorated by more frequent use of organs procured from older or extended criteria donors (ECDs). To eliminate the influence of donor factors on the transplantation results, the pair analysis method was applied. The study aimed to assess the survival, during long-term follow-up after transplantation, of recipients and transplanted kidneys, graft function, and factors influencing survival in recipients aged 60 years and older (≥60) compared to recipients aged less than 60 years (<60) who received a kidney from the same brain death donor (DBD). Methods: The study group consisted of 213 consecutive patients ≥60 who received a kidney procured from a DBD from whom the second procured kidney was transplanted to a patient <60 (control group). Results: The survival rates in the 10-year follow-up period were lower in those recipients ≥60 than in the control group (p < 0.01). The survival rates of the transplanted kidneys were comparable in both groups, while the death-censored graft survival was higher in those patients ≥60 than in the control group (p < 0.05). The estimated glomerular filtration rate levels were similar in the follow-up in patients ≥60 compared to those recipients <60. Transplantation of kidneys procured from ECD, longer duration of dialysis treatment, and longer duration of cold ischemia time (CIT) affected the recipient and graft survival in the ≥60 patients. Death-censored kidney graft survival was influenced by transplantation of a kidney procured from ECD, longer CIT, and the need for reoperation in the early postoperative period. Conclusions: Despite the higher mortality in the kidney recipients ≥60, the long-term results of KTx after the elimination of donor-dependent factors are similar or better compared to the recipients <60. The factors influencing the results of KTx in elderly recipients differ from those observed in the entire cohort and younger patients.
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Affiliation(s)
- Jacek Ziaja
- Department of General, Vascular and Transplant Surgery, Medical University of Silesia, 40-027 Katowice, Poland; (M.W.)
| | - Damian Skrabaka
- Department of Vascular and General Surgery, Provincial Specialist Hospital, 41-902 Bytom, Poland;
| | - Aleksander J. Owczarek
- Health Promotion and Obesity Management Unit, Department of Pathophysiology, Medical University of Silesia, 40-752 Katowice, Poland;
| | - Monika Widera
- Department of General, Vascular and Transplant Surgery, Medical University of Silesia, 40-027 Katowice, Poland; (M.W.)
| | - Robert Król
- Department of General, Vascular and Transplant Surgery, Medical University of Silesia, 40-027 Katowice, Poland; (M.W.)
| | - Aureliusz Kolonko
- Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia, 40-027 Katowice, Poland; (A.K.)
| | - Andrzej Więcek
- Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia, 40-027 Katowice, Poland; (A.K.)
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18
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Breyer I, Ptak L, Stoy D, Mandelbrot D, Parajuli S. Early clearance of BK polyomavirus-DNAemia among kidney transplant recipients may lead to better graft survival. Transpl Infect Dis 2024; 26:e14371. [PMID: 39226142 PMCID: PMC11666869 DOI: 10.1111/tid.14371] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Revised: 08/03/2024] [Accepted: 08/20/2024] [Indexed: 09/05/2024]
Abstract
INTRODUCTION BK polyomavirus (BKPyV)-DNAemia is a common complication in kidney transplant recipients (KTRs). The significance of achieving viral clearance at different time intervals is not well understood. METHODS All adult KTRs transplanted between January 1, 2015 and December 31, 2017 who developed BKPyV-DNAemia were included. Outcomes were analyzed based on persistent clearance of BKPyV-DNAemia at 3-month intervals up to 2 years after initial detection, and for recipients with persistent BKPyV-DNAemia at last follow-up. Uncensored graft failure, death-censored graft failure (DCGF), and a composite outcome of DCGF or fall in estimated glomerular filtration rate (eGFR) by ≥50% from the time of initial BKPyV-DNAemia were outcomes of interest. RESULTS Of 224 KTRs with BKPyV-DNAemia, 58 recipients (26%) achieved viral clearance by 3 months after initial detection, 105 (47%) by 6 months, 120 (54%) by 9 months, 141 (63%) by 12 months, 155 (69%) by 15 months, 167 (75%) by 18 months, 180 (80%) by 21 months, and 193 (86%) by 24 months. Nine recipients (4%) had persistent BKPyV-DNAemia at last follow-up. Compared to recipients who achieved viral clearance by 3 months, those who achieved clearance by 6 months (adjusted odds ratio [aOR]: 3.15; 95% confidence interval [CI]: 1.22-8.12; p = .02) and 9 months (aOR: 3.69; 95% CI: 1.02-13.43; p = .04) had significantly increased risk for uncensored graft failure. There was no significant association between time to viral clearance and DCGF or composite outcomes. CONCLUSIONS We found a trend of increased risk for uncensored graft failure among those who cleared BKPyV-DNAemia more slowly. Aiming to clear viremia early, without risking rejection, may be beneficial for allograft function and patient morbidity and mortality.
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Affiliation(s)
- Isabel Breyer
- Division of Nephrology, Department of MedicineUniversity of Wisconsin School of Medicine and Public HealthMadisonWisconsinUSA
| | - Lucy Ptak
- Division of Nephrology, Department of MedicineUniversity of Wisconsin School of Medicine and Public HealthMadisonWisconsinUSA
| | - David Stoy
- Division of Nephrology, Department of MedicineUniversity of Wisconsin School of Medicine and Public HealthMadisonWisconsinUSA
| | - Didier Mandelbrot
- Division of Nephrology, Department of MedicineUniversity of Wisconsin School of Medicine and Public HealthMadisonWisconsinUSA
| | - Sandesh Parajuli
- Division of Nephrology, Department of MedicineUniversity of Wisconsin School of Medicine and Public HealthMadisonWisconsinUSA
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19
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Santos AH, Mehta R, Alquadan K, Ibrahim H, Leghrouz MA, Belal A, Wen X. Age-modified risk factors for mortality of non-elderly adult kidney transplant recipients: a retrospective database analysis. Int Urol Nephrol 2024; 56:3733-3742. [PMID: 38922533 DOI: 10.1007/s11255-024-04132-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2024] [Accepted: 06/18/2024] [Indexed: 06/27/2024]
Abstract
PURPOSE We aimed to investigate the role of the recipient's age strata in modifying the associations between risk factors and mortality in non-elderly adult kidney transplant (KT) recipients (KTR). METHODS We stratified 108,695 adult KTRs between 2000 and 2016 with conditional 1-year survival after KT into cohorts based on age at transplant: 18-49 years and 50-64 years. We excluded KTRs aged < 18 years or > / = 65 years. KTRs were observed for 5 years during the 2nd through 6th years post-KT for the outcome, all-cause mortality. RESULTS Increasing recipient age strata (18-49-year-old and 50-64-year-old) correlated with decreasing 6-year post-KT survival rates conditional on 1-year survival (79% and 57%, respectively, p < 0.0001). Middle adult age stratum was associated with a higher risk of all-cause mortality than young adult age stratum in KTRs of Hispanic/Latino and other races [HR = 1.23, 95% CI = 1.04-1.45 and HR = 1.51, 95% CI = 1.16-1.97, respectively] and with a primary native renal diagnosis of hypertension or glomerulonephritis [HR = 1.32, 95% CI = 1.12-1.55 and HR = 1.29, 95% CI = 1.10-151, respectively]. When compared with the young adult age stratum, the middle adult age stratum had a mitigating effect on the higher risk of mortality associated with sirolimus-mycophenolate or sirolimus-tacrolimus than the standard calcineurin inhibitor-mycophenolate regimen [HR = 0.75, 95% CI = 0.57-0.99 and HR = 0.71, 95% CI = 0.57-0.89, respectively]. CONCLUSION Among adult non-elderly KTRs, the age strata, 18-49 years, and 50-64 years, have varying modifying effects on the strength and direction of associations between some specific risk factors and all-cause mortality.
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Affiliation(s)
- Alfonso H Santos
- Division of Nephrology, Hypertension and Renal Transplantation, Department of Medicine, College of Medicine, University of Florida, 1600 SW Archer Road, Medical Science Bldg., Room NG-4, Gainesville, FL, 32610, USA.
| | - Rohan Mehta
- Division of Nephrology, Hypertension and Renal Transplantation, Department of Medicine, College of Medicine, University of Florida, 1600 SW Archer Road, Medical Science Bldg., Room NG-4, Gainesville, FL, 32610, USA
| | - Kawther Alquadan
- Division of Nephrology, Hypertension and Renal Transplantation, Department of Medicine, College of Medicine, University of Florida, 1600 SW Archer Road, Medical Science Bldg., Room NG-4, Gainesville, FL, 32610, USA
| | - Hisham Ibrahim
- Division of Nephrology, Hypertension and Renal Transplantation, Department of Medicine, College of Medicine, University of Florida, 1600 SW Archer Road, Medical Science Bldg., Room NG-4, Gainesville, FL, 32610, USA
| | - Muhannad A Leghrouz
- Division of Nephrology, Hypertension and Renal Transplantation, Department of Medicine, College of Medicine, University of Florida, 1600 SW Archer Road, Medical Science Bldg., Room NG-4, Gainesville, FL, 32610, USA
| | - Amer Belal
- Division of Nephrology, Hypertension and Renal Transplantation, Department of Medicine, College of Medicine, University of Florida, 1600 SW Archer Road, Medical Science Bldg., Room NG-4, Gainesville, FL, 32610, USA
| | - Xuerong Wen
- Department of Pharmacy Practice, College of Pharmacy, University of Rhode Island, Kingston, RI, USA
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20
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Demir E, Dincer MT, Karaca C, Erel C, Karahan L, Pekmezci A, Trabulus S, Seyahi N, Turkmen A. Does de novo malignancy heighten the risk of rejection in kidney transplant recipients? Clin Kidney J 2024; 17:sfae349. [PMID: 39678249 PMCID: PMC11646098 DOI: 10.1093/ckj/sfae349] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2024] [Indexed: 12/17/2024] Open
Abstract
Background Malignancies are the third leading cause of death among kidney transplant recipients. These patients face increased mortality and challenges such as allograft loss and rejection, which may arise from surgical complications, changes in immunosuppressive therapy or the use of chemotherapeutics. This study aims to examine the risk of allograft rejection and loss in kidney transplant recipients diagnosed with de novo malignancies. Methods This retrospective case-control study included adult kidney transplant patients from 1986 to 2020 who developed de novo malignancies. Each patient with a malignancy was matched with a control without malignancy using the nearest neighbor matching method. The outcomes measured were biopsy-confirmed allograft rejection, death-censored allograft loss and overall mortality after the diagnosis of malignancy in the malignancy group and at any point in the control group. Results Of 2750 records reviewed, 267 patients (9.7%) had biopsy-confirmed malignancies, with a median age of 60 years and 66.3% men. The median follow-up was 218 months. Kaplan-Meier analysis showed that the allograft rejection rates were lower in the malignancy group compared with the control group (26 vs 60, P < .001). Overall mortality was higher in the malignancy group, although this difference was not statistically significant (104 vs 73, P = .25). Death-censored allograft loss was similar between groups (22 vs 32, P = .49). Chemotherapy and older recipient age were associated with reduced allograft rejection risk, as indicated by multivariable regression analysis. Conclusions In kidney transplant recipients with de novo malignancies, death with a functioning graft remains significant. However, allograft loss rates do not increase compared with those without malignancies, and rejection risk is reduced, especially in older and chemotherapy-treated patients. These findings suggest that managing immunosuppression reduction in this population may be appropriate, but further research is needed to determine optimal care strategies.
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Affiliation(s)
- Erol Demir
- Transplant Immunology Research Center of Excellence, Koç University Hospital, Koç University, Istanbul, Türkiye
| | - Mevlut Tamer Dincer
- Division of Nephrology, Department of Internal Medicine, Cerrahpaşa Faculty of Medicine, Istanbul University Cerrahpaşa, Istanbul, Türkiye
| | - Cebrail Karaca
- Division of Nephrology, Department of Internal Medicine, Cerrahpaşa Faculty of Medicine, Istanbul University Cerrahpaşa, Istanbul, Türkiye
| | - Cansu Erel
- Division of Nephrology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye
| | - Latif Karahan
- Division of Nephrology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye
| | - Aslihan Pekmezci
- Division of Nephrology, Department of Internal Medicine, Cerrahpaşa Faculty of Medicine, Istanbul University Cerrahpaşa, Istanbul, Türkiye
| | - Sinan Trabulus
- Division of Nephrology, Department of Internal Medicine, Cerrahpaşa Faculty of Medicine, Istanbul University Cerrahpaşa, Istanbul, Türkiye
| | - Nurhan Seyahi
- Division of Nephrology, Department of Internal Medicine, Cerrahpaşa Faculty of Medicine, Istanbul University Cerrahpaşa, Istanbul, Türkiye
| | - Aydin Turkmen
- Division of Nephrology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye
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21
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Sexton DJ, Bagnasco S, Kant S. Transplant Nephrology. ADVANCES IN KIDNEY DISEASE AND HEALTH 2024; 31:566-573. [PMID: 39577891 DOI: 10.1053/j.akdh.2024.08.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Revised: 07/25/2024] [Accepted: 08/05/2024] [Indexed: 11/24/2024]
Abstract
The progressive rise in the number of kidney transplant recipients in the last 2 decades is reflective of the technological advances in the field. Nephrologists are responsible for providing long-term longitudinal care to these patients. It is pertinent that nephrologists understand the various nuances of aspects such as immunosuppression, opportunistic infections, and identification of causes associated with graft dysfunction.
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Affiliation(s)
- Donal J Sexton
- Department of Renal Medicine, St. James Hospital, Trinity College School of Medicine, Dublin, Ireland
| | - Serena Bagnasco
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Sam Kant
- Department of Renal Medicine, Cork University Hospital, University College Cork School of Medicine, Cork, Ireland.
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22
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Fernández-Ruiz M, Ruiz-Merlo T, Rodríguez-Goncer I, Caso JM, López-Medrano F, Parra P, San Juan R, Polanco N, González E, Andrés A, Aguado JM, Redondo N. Performance of a Global Functional Assay Based on Interferon-γ Release to Predict Infectious Complications and Cancer After Kidney Transplantation. Transpl Int 2024; 37:13551. [PMID: 39539802 PMCID: PMC11557340 DOI: 10.3389/ti.2024.13551] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Accepted: 10/22/2024] [Indexed: 11/16/2024]
Abstract
The QuantiFERON-Monitor assay (QTF-Monitor) is intended to assess innate and adaptive immune responses by quantifying interferon (IFN)-γ release upon whole blood stimulation with a TLR7/8 agonist and an anti-CD3 antibody. We performed the QTF-Monitor in 126 kidney transplant recipients (KTRs) at different points during the first 6 post-transplant months. The primary outcome was overall infection, whereas secondary outcomes included bacterial infection, opportunistic infection and de novo cancer. The association between IFN-γ production and outcomes was analyzed as "low" immune responses (<15 IU/mL) and as a continuous variable to explore alternative thresholds. There were no significant differences in the occurrence of overall infection according to the QTF-Monitor at any monitoring point. Regarding secondary outcomes, KTRs with a low response at week 2 experienced a higher incidence of bacterial infection (50.8% versus 24.4%; P-value = 0.006). Low response at month 1 was also associated with opportunistic infection (31.6% versus 14.3%; P-value = 0.033). The discriminative capacity of IFN-γ levels was poor (areas under the ROC curve: 0.677 and 0.659, respectively). No differences were observed for the remaining points or post-transplant cancer. In conclusion, the QTF-Monitor may have a role to predict bacterial and opportunistic infection in KTRs when performed early after transplantation.
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Affiliation(s)
- Mario Fernández-Ruiz
- Unit of Infectious Diseases, Hospital Universitario “12 de Octubre”, Instituto de Investigación Sanitaria Hospital “12 de Octubre” (imas12), Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
- Department of Medicine, School of Medicine, Universidad Complutense, Madrid, Spain
| | - Tamara Ruiz-Merlo
- Unit of Infectious Diseases, Hospital Universitario “12 de Octubre”, Instituto de Investigación Sanitaria Hospital “12 de Octubre” (imas12), Madrid, Spain
| | - Isabel Rodríguez-Goncer
- Unit of Infectious Diseases, Hospital Universitario “12 de Octubre”, Instituto de Investigación Sanitaria Hospital “12 de Octubre” (imas12), Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
| | - José María Caso
- Unit of Infectious Diseases, Hospital Universitario “12 de Octubre”, Instituto de Investigación Sanitaria Hospital “12 de Octubre” (imas12), Madrid, Spain
| | - Francisco López-Medrano
- Unit of Infectious Diseases, Hospital Universitario “12 de Octubre”, Instituto de Investigación Sanitaria Hospital “12 de Octubre” (imas12), Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
- Department of Medicine, School of Medicine, Universidad Complutense, Madrid, Spain
| | - Patricia Parra
- Unit of Infectious Diseases, Hospital Universitario “12 de Octubre”, Instituto de Investigación Sanitaria Hospital “12 de Octubre” (imas12), Madrid, Spain
| | - Rafael San Juan
- Unit of Infectious Diseases, Hospital Universitario “12 de Octubre”, Instituto de Investigación Sanitaria Hospital “12 de Octubre” (imas12), Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
- Department of Medicine, School of Medicine, Universidad Complutense, Madrid, Spain
| | - Natalia Polanco
- Department of Medicine, School of Medicine, Universidad Complutense, Madrid, Spain
- Department of Nephrology, Hospital Universitario “12 de Octubre”, Instituto de Investigación Sanitaria Hospital “12 de Octubre” (imas12), Madrid, Spain
| | - Esther González
- Department of Medicine, School of Medicine, Universidad Complutense, Madrid, Spain
- Department of Nephrology, Hospital Universitario “12 de Octubre”, Instituto de Investigación Sanitaria Hospital “12 de Octubre” (imas12), Madrid, Spain
| | - Amado Andrés
- Department of Medicine, School of Medicine, Universidad Complutense, Madrid, Spain
- Department of Nephrology, Hospital Universitario “12 de Octubre”, Instituto de Investigación Sanitaria Hospital “12 de Octubre” (imas12), Madrid, Spain
| | - José María Aguado
- Unit of Infectious Diseases, Hospital Universitario “12 de Octubre”, Instituto de Investigación Sanitaria Hospital “12 de Octubre” (imas12), Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
- Department of Medicine, School of Medicine, Universidad Complutense, Madrid, Spain
| | - Natalia Redondo
- Unit of Infectious Diseases, Hospital Universitario “12 de Octubre”, Instituto de Investigación Sanitaria Hospital “12 de Octubre” (imas12), Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
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23
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Pencovich N, Smith BH, Attia ZI, Jimenez FL, Bentall AJ, Schinstock CA, Khamash HA, Jadlowiec CC, Jarmi T, Mao SA, Park WD, Diwan TS, Friedman PA, Stegall MD. Electrocardiography-based Artificial Intelligence Algorithms Aid in Prediction of Long-term Mortality After Kidney Transplantation. Transplantation 2024; 108:1976-1985. [PMID: 38557657 DOI: 10.1097/tp.0000000000005023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/04/2024]
Abstract
BACKGROUND Predicting long-term mortality postkidney transplantation (KT) using baseline clinical data presents significant challenges. This study aims to evaluate the predictive power of artificial intelligence (AI)-enabled analysis of preoperative electrocardiograms (ECGs) in forecasting long-term mortality following KT. METHODS We analyzed preoperative ECGs from KT recipients at three Mayo Clinic sites (Minnesota, Florida, and Arizona) between January 1, 2006, and July 30, 2021. The study involved 6 validated AI algorithms, each trained to predict future development of atrial fibrillation, aortic stenosis, low ejection fraction, hypertrophic cardiomyopathy, amyloid heart disease, and biological age. These algorithms' outputs based on a single preoperative ECG were correlated with patient mortality data. RESULTS Among 6504 KT recipients included in the study, 1764 (27.1%) died within a median follow-up of 5.7 y (interquartile range: 3.00-9.29 y). All AI-ECG algorithms were independently associated with long-term all-cause mortality ( P < 0.001). Notably, few patients had a clinical cardiac diagnosis at the time of transplant, indicating that AI-ECG scores were predictive even in asymptomatic patients. When adjusted for multiple clinical factors such as recipient age, diabetes, and pretransplant dialysis, AI algorithms for atrial fibrillation and aortic stenosis remained independently associated with long-term mortality. These algorithms also improved the C-statistic for predicting overall (C = 0.74) and cardiac-related deaths (C = 0.751). CONCLUSIONS The findings suggest that AI-enabled preoperative ECG analysis can be a valuable tool in predicting long-term mortality following KT and could aid in identifying patients who may benefit from enhanced cardiac monitoring because of increased risk.
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Affiliation(s)
- Niv Pencovich
- Departments of Surgery and Immunology, William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN
- Department of General Surgery and Transplantation, Sheba Medical Center, Tel Hashomer, Tel-Aviv University, Tel-Aviv, Israel
| | - Byron H Smith
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN
| | - Zachi I Attia
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN
| | | | - Andrew J Bentall
- Departments of Surgery and Immunology, William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN
| | - Carrie A Schinstock
- Departments of Surgery and Immunology, William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN
| | | | | | - Tambi Jarmi
- Department of Transplant, Mayo Clinic Florida, Jacksonville, FL
| | - Shennen A Mao
- Division of Transplant Surgery, Department of Surgery, Mayo Clinic, Phoenix, AZ
| | - Walter D Park
- Departments of Surgery and Immunology, William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN
| | - Tayyab S Diwan
- Departments of Surgery and Immunology, William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN
| | - Paul A Friedman
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN
| | - Mark D Stegall
- Departments of Surgery and Immunology, William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN
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24
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Laowalert S, Naitook N, Boonnim K, Prungrit U, Aekkachaipitak N, Lamjantuek P, Liwlompaisan W, Khunprakant R, Techawathanawanna N, Mavichak V, Udomkarnjananun S. Report on post-transplantation cancer in southeast Asia from the Thai kidney transplantation cohort. Sci Rep 2024; 14:20154. [PMID: 39215076 PMCID: PMC11364626 DOI: 10.1038/s41598-024-71041-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Accepted: 08/23/2024] [Indexed: 09/04/2024] Open
Abstract
Post-transplantation cancer is a significant cause of mortality among kidney transplant recipients (KTR). The incidence of post-transplantation cancer varies based on geographic region and ethnicity. However, data on KTR from South East Asia, where characteristics differ from other parts of Asia, is lacking. We conducted a retrospective cohort study at a transplant center in Thailand to investigate the incidence of post-transplantation cancer and mortality rates. Factors associated with post-transplantation cancer and patient outcomes were analyzed using competing-risks regression. The study included 1156 KTR with a post-transplant follow-up duration of 5.1 (2.7-9.4) years. The age- and sex-adjusted incidence rate of post-transplant cancer was highest for urothelial cancer (6.9 per 1000 person-years), which also resulted in the highest standardized incidence ratio (SIR) of 42.5 when compared to the general population. Kidney cancer had the second-highest SIR of 24.4. Increasing age was the factor associated with an increased risk of post-transplant cancer (SHR 1.03; 95% CI 1.01-1.05). Human leukocyte antigen (HLA) DR mismatch was associated with a decreased risk of post-transplant cancer (SHR 0.72; 95% CI 0.52-0.98). Post-transplantation cancer was significantly associated with patient mortality (HR 3.16; 95% CI 2.21-4.52). Cancer significantly contributes to KTR mortality, and the risk profile for cancer development in Thai KTRs differs from that of Western and most Asian counterparts. Further research is essential to explore appropriate screening protocols for countries with high rates of urothelial and kidney cancer, including Thailand.
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Affiliation(s)
| | - Nattakan Naitook
- Kidney Transplant Institute, Praram 9 Hospital, Bangkok, Thailand
| | - Kesawan Boonnim
- Kidney Transplant Institute, Praram 9 Hospital, Bangkok, Thailand
| | - Uayporn Prungrit
- Kidney Transplant Institute, Praram 9 Hospital, Bangkok, Thailand
| | | | | | | | | | | | - Viroon Mavichak
- Kidney Transplant Institute, Praram 9 Hospital, Bangkok, Thailand
| | - Suwasin Udomkarnjananun
- Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, 1873, Rama 4 Road, Pathumwan, 10330, Bangkok, Thailand.
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25
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Khurana S, Shipley M, Chandler T, Furmanek S, Ramirez J, Cavallazzi R. Clinical characteristics and outcomes of community-acquired pneumonia in solid organ transplant recipients. Respir Med 2024; 230:107698. [PMID: 38848822 DOI: 10.1016/j.rmed.2024.107698] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Revised: 05/30/2024] [Accepted: 06/05/2024] [Indexed: 06/09/2024]
Abstract
BACKGROUND Pneumonia is a frequent complication of solid organ transplantation that adversely impacts both graft and recipient survival. There is a paucity of data on community-acquired pneumonia (CAP) in transplant recipients, particularly the long term outcomes. We conducted a study to compare the clinical characteristics and outcomes of pneumonia in solid organ transplant (SOT) recipients to those in non-transplant (NT) recipients. MATERIAL AND METHODS Clinical characteristics were abstracted from electronic medical records. Outcomes included time to hospital discharge, short and long-term mortality. Inverse-propensity score weights were assigned to account for between-group differences. Adjusted analysis included a weighted logistic regression. Results were reported as odds ratios with a corresponding 95 % confidence interval (CI). RESULTS A total of 7449 patients were admitted with CAP. Patients were divided into two groups: SOT recipients 42 (0.56 %) and NT recipients 7396 (99.2 %). SOT recipients were younger, more commonly males, with higher prevalence of comorbidities. After accounting for inverse-propensity score weighting, the odds of mortality were higher in SOT recipients in hospital, at 30 days and at 1 year. The magnitude of increase in mortality for SOT recipients was greatest at 1 year with 1.41 (95 % CI: 1.38-1.44) times higher odds. CONCLUSION In patients with CAP, SOT recipients are younger, more commonly male and have more co-morbidities compared with NT recipients. They also have higher 1 year mortality after adjustment. Clinicians must be vigilant toward the pronounced long-term mortality risk among these patients and ensure continued follow-up care for them.
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Affiliation(s)
- Shriya Khurana
- Division of Pulmonary, Critical Care & Sleep Disorder Medicine, University of Louisville, Louisville, KY, USA.
| | - Madeline Shipley
- Norton Infectious Diseases Institute, Norton Healthcare, Louisville, KY, USA
| | - Thomas Chandler
- Norton Infectious Diseases Institute, Norton Healthcare, Louisville, KY, USA
| | - Stephen Furmanek
- Norton Infectious Diseases Institute, Norton Healthcare, Louisville, KY, USA
| | - Julio Ramirez
- Norton Infectious Diseases Institute, Norton Healthcare, Louisville, KY, USA
| | - Rodrigo Cavallazzi
- Division of Pulmonary, Critical Care & Sleep Disorder Medicine, University of Louisville, Louisville, KY, USA
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26
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Alotaibi NE. Incidence and risk factors of infections following kidney transplantation. J Infect Public Health 2024; 17:102491. [PMID: 38996795 DOI: 10.1016/j.jiph.2024.102491] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Revised: 06/27/2024] [Accepted: 06/30/2024] [Indexed: 07/14/2024] Open
Abstract
BACKGROUND For patients with End-Stage Renal Disease (ESRD), kidney transplantation stands as the superior alternative to dialysis, exhibiting enhancements in both quality of life and survival rates. The objective of this study is to ascertain the prevalence of infections and associated risk factors within the initial two years post-renal transplant. METHOD A retrospective study of all renal transplant recipients who underwent renal transplantation at king Abdullah medical city in Makkah, Saudi Arabia from January 1st, 2018, till end of December 2021 followed up for two years. RESULTS A total of 43 patients were included in the study, The participants who experienced infectious episodes had a higher mean age, averaging 45.26 ± 14, in contrast to those who did not, averaging 38.75 ± 12. Most of the patients included in the study were male, 70 % of the total population. However, most infectious complications occurred in women (77 % vs. 30 %, respectively, p-value 0.004). Regarding the mode of dialysis before the transplantation, most of the patients were maintained on hemodialysis (76.7 %), and the mean duration of dialysis was longer on those presented with infections within two years post-transplant compared to those without it (3.26 ± 1.6 vs. 2 ± 1.14 years respectively). The incidence of the infections was 44.2 % (19 individuals). The most common presented infections in the patients within two years post renal transplant were urinary tract infections (20.9 %), with a high recurrence rate reaching 11.6 %. This was followed by Coronavirus disease (COVID-19) and Cytomegalovirus (CMV). CONCLUSION This study sheds light on the prevalence of infectious complications following renal transplantation and highlights specific risk factors associated with these infections. Understanding these patterns can aid in the development of preventive strategies and optimized care for transplant recipients during the early post-transplant period.
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Affiliation(s)
- Nouf E Alotaibi
- Umm Al-Qura University, Pharmacy Practices Department, College of Pharmacy, Makkah, Saudi Arabia.
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27
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Ma BM, Elefant N, Tedesco M, Bogyo K, Vena N, Murthy SK, Bheda SA, Yang S, Tomar N, Zhang JY, Husain SA, Mohan S, Kiryluk K, Rasouly HM, Gharavi AG. Developing a genetic testing panel for evaluation of morbidities in kidney transplant recipients. Kidney Int 2024; 106:115-125. [PMID: 38521406 PMCID: PMC11410071 DOI: 10.1016/j.kint.2024.02.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Revised: 01/18/2024] [Accepted: 02/13/2024] [Indexed: 03/25/2024]
Abstract
Cardiovascular disease, infection, malignancy, and thromboembolism are major causes of morbidity and mortality in kidney transplant recipients (KTR). Prospectively identifying monogenic conditions associated with post-transplant complications may enable personalized management. Therefore, we developed a transplant morbidity panel (355 genes) associated with major post-transplant complications including cardiometabolic disorders, immunodeficiency, malignancy, and thrombophilia. This gene panel was then evaluated using exome sequencing data from 1590 KTR. Additionally, genes associated with monogenic kidney and genitourinary disorders along with American College of Medical Genetics (ACMG) secondary findings v3.2 were annotated. Altogether, diagnostic variants in 37 genes associated with Mendelian kidney and genitourinary disorders were detected in 9.9% (158/1590) of KTR; 25.9% (41/158) had not been clinically diagnosed. Moreover, the transplant morbidity gene panel detected diagnostic variants for 56 monogenic disorders in 9.1% KTRs (144/1590). Cardiovascular disease, malignancy, immunodeficiency, and thrombophilia variants were detected in 5.1% (81), 2.1% (34), 1.8% (29) and 0.2% (3) among 1590 KTRs, respectively. Concordant phenotypes were present in half of these cases. Reviewing implications for transplant care, these genetic findings would have allowed physicians to set specific risk factor targets in 6.3% (9/144), arrange intensive surveillance in 97.2% (140/144), utilize preventive measures in 13.2% (19/144), guide disease-specific therapy in 63.9% (92/144), initiate specialty referral in 90.3% (130/144) and alter immunosuppression in 56.9% (82/144). Thus, beyond diagnostic testing for kidney disorders, sequence annotation identified monogenic disorders associated with common post-transplant complications in 9.1% of KTR, with important clinical implications. Incorporating genetic diagnostics for transplant morbidities would enable personalized management in pre- and post-transplant care.
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Affiliation(s)
- Becky M Ma
- Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, New York, USA; Department of Medicine, Center for Precision Medicine and Genomics, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA; Division of Nephrology, Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong, China
| | - Naama Elefant
- Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, New York, USA; Department of Medicine, Center for Precision Medicine and Genomics, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA
| | - Martina Tedesco
- Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, New York, USA; Department of Medicine, Center for Precision Medicine and Genomics, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA; Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy
| | - Kelsie Bogyo
- Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, New York, USA; Department of Medicine, Center for Precision Medicine and Genomics, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA
| | - Natalie Vena
- Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, New York, USA; Department of Medicine, Center for Precision Medicine and Genomics, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA
| | - Sarath K Murthy
- Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, New York, USA; Department of Medicine, Center for Precision Medicine and Genomics, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA
| | - Shiraz A Bheda
- Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, New York, USA; Department of Medicine, Center for Precision Medicine and Genomics, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA
| | - Sandy Yang
- Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, New York, USA; Department of Medicine, Center for Precision Medicine and Genomics, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA
| | - Nikita Tomar
- Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, New York, USA; Department of Medicine, Center for Precision Medicine and Genomics, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA
| | - Jun Y Zhang
- Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, New York, USA; Department of Medicine, Center for Precision Medicine and Genomics, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA
| | - Syed Ali Husain
- Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, New York, USA
| | - Sumit Mohan
- Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, New York, USA
| | - Krzysztof Kiryluk
- Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, New York, USA; Department of Medicine, Center for Precision Medicine and Genomics, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA
| | - Hila Milo Rasouly
- Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, New York, USA; Department of Medicine, Center for Precision Medicine and Genomics, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA
| | - Ali G Gharavi
- Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, New York, USA; Department of Medicine, Center for Precision Medicine and Genomics, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA.
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Vinson AJ, Zhang X, Dahhou M, Süsal C, Döhler B, Sapir-Pichhadze R, Cardinal H, Melk A, Wong G, Francis A, Pilmore H, Foster BJ. A Multinational Cohort Study Examining Sex Differences in Excess Risk of Death With Graft Function After Kidney Transplant. Transplantation 2024; 108:1448-1459. [PMID: 38277260 DOI: 10.1097/tp.0000000000004915] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2024]
Abstract
BACKGROUND Kidney transplant recipients show sex differences in excess overall mortality risk that vary by donor sex and recipient age. However, whether the excess risk of death with graft function (DWGF) differs by recipient sex is unknown. METHODS In this study, we combined data from 3 of the largest transplant registries worldwide (Scientific Registry of Transplant Recipient, Australia and New Zealand Dialysis and Transplant Registry, and Collaborative Transplant Study) using individual patient data meta-analysis to compare the excess risk of DWGF between male and female recipients of a first deceased donor kidney transplant (1988-2019), conditional on donor sex and recipient age. RESULTS Among 463 895 individuals examined, when the donor was male, female recipients aged 0 to 12 y experienced a higher excess risk of DWGF than male recipients (relative excess risk 1.68; 95% confidence interval, 1.24-2.29); there were no significant differences in other age intervals or at any age when the donor was female. There was no statistically significant between-cohort heterogeneity. CONCLUSIONS Given the lack of sex differences in the excess risk of DWGF (other than in prepubertal recipients of a male donor kidney) and the known greater excess overall mortality risk for female recipients compared with male recipients in the setting of a male donor, future study is required to characterize potential sex-specific causes of death after graft loss.
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Affiliation(s)
- Amanda Jean Vinson
- Nephrology Division, Department of Medicine, Dalhousie University, Halifax, NS, Canada
| | - Xun Zhang
- Research Institute of the McGill University Health Centre, Montreal, QC, Canada
| | - Mourad Dahhou
- Research Institute of the McGill University Health Centre, Montreal, QC, Canada
| | - Caner Süsal
- Institute of Immunology, Heidelberg University Hospital, Heidelberg, Germany
- Transplant Immunology Research Center of Excellence, Koç University, Istanbul, Turkey
| | - Bernd Döhler
- Institute of Immunology, Heidelberg University Hospital, Heidelberg, Germany
| | - Ruth Sapir-Pichhadze
- Department of Medicine, Division of Experimental Medicine, McGill University, QC, Canada
| | - Heloise Cardinal
- Division of Nephrology, Department of Medicine, Centre Hospitalier de l'Université de Montreal, Montreal, QC, Canada
| | - Anette Melk
- Children's Hospital, Hannover Medical School, Hannover, Germany
| | - Germaine Wong
- School of Public Health, University of Sydney, Sydney, NSW, Australia
| | - Anna Francis
- School of Clinical Medicine, University of Queensland, QLD, Australia
- Department of Medicine, Division of Nephrology, Queensland Children's Hospital, Brisbane, QLD, Australia
| | - Helen Pilmore
- Department of Renal Medicine, Auckland City Hospital, Auckland, New Zealand
| | - Bethany J Foster
- Research Institute of the McGill University Health Centre, Montreal, QC, Canada
- Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC, Canada
- Division of Nephrology, Department of Pediatrics, McGill University Faculty of Medicine, QC, Canada
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29
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Hosek N, Montani M, Mani LY. Acute post-renal kidney graft dysfunction due to cytomegalovirus-positive nephrogenic adenoma-case report and review of the literature. Front Med (Lausanne) 2024; 11:1394028. [PMID: 38873192 PMCID: PMC11175655 DOI: 10.3389/fmed.2024.1394028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Accepted: 05/09/2024] [Indexed: 06/15/2024] Open
Abstract
Tissue-invasive cytomegalovirus (CMV) disease represents a well-recognized complication after kidney transplantation. However, direct involvement of the urogenital tract and CMV-ureteritis occur less frequently. Nephrogenic adenomas are benign lesions of the urinary tract preferentially reported in kidney transplant recipients. We herein report a second case of a 33-year-old male kidney transplant recipient with acute post-renal allograft dysfunction due to CMV-positive ureteral nephrogenic adenoma. A causal connection might be suspected but remains to be proven.
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Affiliation(s)
- Nicola Hosek
- Department of Medicine, Division of Nephrology and Dialysis, Kantonsspital Graubünden, Chur, Switzerland
- Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Matteo Montani
- Institute of Tissue Medicine and Pathology, University of Bern, Bern, Switzerland
| | - Laila-Yasmin Mani
- Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
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30
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Shamshad F, Tungsanga S, Senior P, Shojai S, Ghimire A, Ye F, Kung JY, Hariramani VK, Abdulrahman A, Penney M, Sultana N, Muneer S, Okpechi I, Bello AK. Effect of metformin use on graft and patient survival in kidney transplant recipients with type 2 diabetes: a systematic review protocol. BMJ Open 2024; 14:e078393. [PMID: 38760033 PMCID: PMC11103231 DOI: 10.1136/bmjopen-2023-078393] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Accepted: 04/26/2024] [Indexed: 05/19/2024] Open
Abstract
INTRODUCTION Metformin is a first-line antihyperglycaemic agent for type 2 diabetes (T2DM). In addition to glycaemic control, it offers benefits related to cardiovascular health, weight neutrality and metabolic syndrome. However, its benefits in kidney transplant recipients remain unclear as metformin use is controversial in this population due to a lack of evidence and there are recommendations against its use in patients with poor kidney function. Hence, we seek to describe a protocol for a systematic review, which will assess the impact of metformin use on graft survival and mortality in kidney transplant recipients. METHODS This protocol was guided by the standards of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols 2015. We will search empirical databases such as MEDLINE, Embase, Cochrane Library, CINAHL and Web of Science Core Collection for relevant studies conducted in kidney transplant recipients using metformin, which report outcomes related to graft and patient survival. All studies meeting these criteria in adults and published in English from inception to 2023 will be included in our review. We will employ the Cochrane Risk of Bias Tool 2 for randomised controlled trials and the Risk of Bias in Non-randomised Studies of Intervention for non-randomised studies. We will present our data and study characteristics in a table format and determine if a meta-analysis can be performed by clinical and methodological heterogeneity, using the I2 statistics. If a meta-analysis cannot be performed, we will provide a narrative synthesis of included studies using the Synthesis Without Meta-Analysis Reporting Guideline. ETHICS AND DISSEMINATION Ethical approval will not be required for this review as the data used will be extracted from already published studies with publicly accessible data. As this study will assess the impact of metformin use on graft and patient survival in kidney transplant recipients, evidence gathered through it will be disseminated using traditional approaches that include open-access peer-reviewed publication, scientific presentations and a report. We will also disseminate our findings to appropriate academic bodies in charge of publishing guidelines related to T2DM and transplantation, as well as patient and research centred groups. PROSPERO REGISTRATION NUMBER CRD42023421799.
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Affiliation(s)
- Farooq Shamshad
- Division of Nephrology and Immunology, University of Alberta Faculty of Medicine & Dentistry, Edmonton, Alberta, Canada
| | - Somkanya Tungsanga
- Division of Nephrology and Immunology, University of Alberta Faculty of Medicine & Dentistry, Edmonton, Alberta, Canada
- Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Peter Senior
- Endocrinology & Metabolism, University of Alberta Faculty of Medicine and Dentistry, Edmonton, Alberta, Canada
| | - Soroush Shojai
- Division of Nephrology, Department of Medicine, University of Alberta Faculty of Medicine and Dentistry, Edmonton, Alberta, Canada
| | - Anukul Ghimire
- Division of Nephrology and Immunology, University of Alberta Faculty of Medicine & Dentistry, Edmonton, Alberta, Canada
- Division of Nephrology, University of Calgary, Calgary, Alberta, Canada
| | - Feng Ye
- University of Alberta, Edmonton, Alberta, Canada
| | - Janice Y Kung
- John W. Scott Health Sciences Library, University of Alberta, Edmonton, Alberta, Canada
| | - Vinash K Hariramani
- Division of Nephrology and Immunology, University of Alberta Faculty of Medicine & Dentistry, Edmonton, Alberta, Canada
| | - Abdullah Abdulrahman
- Division of Nephrology and Immunology, University of Alberta Faculty of Medicine & Dentistry, Edmonton, Alberta, Canada
| | - Matthew Penney
- Division of Nephrology and Immunology, University of Alberta Faculty of Medicine & Dentistry, Edmonton, Alberta, Canada
| | - Naima Sultana
- Division of Nephrology and Immunology, University of Alberta Faculty of Medicine & Dentistry, Edmonton, Alberta, Canada
| | - Shezel Muneer
- Division of Nephrology and Immunology, University of Alberta Faculty of Medicine & Dentistry, Edmonton, Alberta, Canada
| | | | - Aminu K Bello
- Division of Nephrology and Immunology, University of Alberta Faculty of Medicine & Dentistry, Edmonton, Alberta, Canada
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31
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Schreiber PW, Hoessly LD, Boggian K, Neofytos D, van Delden C, Egli A, Dickenmann M, Hirzel C, Manuel O, Koller M, Rossi S, Banz V, Schmied B, Guerke L, Matter M, de Rougemont O, Bonani M, Golshayan D, Schnyder A, Sidler D, Haidar F, Kuster SP, Stampf S, Mueller NJ. Surgical site infections after kidney transplantation are independently associated with graft loss. Am J Transplant 2024; 24:795-802. [PMID: 38042413 DOI: 10.1016/j.ajt.2023.11.013] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2023] [Revised: 11/20/2023] [Accepted: 11/23/2023] [Indexed: 12/04/2023]
Abstract
Surgical site infections (SSIs) are common health care-associated infections. SSIs after kidney transplantation (K-Tx) can endanger patient and allograft survival. Multicenter studies on this early posttransplant complication are scarce. We analyzed consecutive adult K-Tx recipients enrolled in the Swiss Transplant Cohort Study who received a K-Tx between May 2008 and September 2020. All data were prospectively collected with the exception of the categorization of SSI which was performed retrospectively according to the Centers for Disease Control and Prevention criteria. A total of 58 out of 3059 (1.9%) K-Tx recipients were affected by SSIs. Deep incisional (15, 25.9%) and organ/space infections (34, 58.6%) predominated. In the majority of SSIs (52, 89.6%), bacteria were detected, most frequently Escherichia coli (15, 28.9%), Enterococcus spp. (14, 26.9%), and coagulase-negative staphylococci (13, 25.0%). A BMI ≥25 kg/m2 (multivariable OR 2.16, 95% CI 1.07-4.34, P = .023) and delayed graft function (multivariable OR 2.88, 95% CI 1.56-5.34, P = .001) were independent risk factors for SSI. In Cox proportional hazard models, SSI was independently associated with graft loss (multivariable HR 3.75, 95% CI 1.35-10.38, P = .011). In conclusion, SSI was a rare complication after K-Tx. BMI ≥25 kg/m2 and delayed graft function were independent risk factors. SSIs were independently associated with graft loss.
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Affiliation(s)
- Peter W Schreiber
- Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich and University Zurich, Zurich, Switzerland.
| | - Linard D Hoessly
- Clinic for Transplantation Immunology and Nephrology, Basel University Hospital, Basel, Switzerland
| | - Katia Boggian
- Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland
| | - Dionysios Neofytos
- Transplant Infectious Diseases Unit, Service of Infectious Diseases, University Hospitals Geneva, University of Geneva, Geneva, Switzerland
| | - Christian van Delden
- Transplant Infectious Diseases Unit, Service of Infectious Diseases, University Hospitals Geneva, University of Geneva, Geneva, Switzerland
| | - Adrian Egli
- Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland
| | - Michael Dickenmann
- Clinic for Transplantation Immunology and Nephrology, Basel University Hospital, Basel, Switzerland
| | - Cédric Hirzel
- Department of Infectious Diseases, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Oriol Manuel
- Infectious Diseases Service, University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland; Transplantation Center, University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
| | - Michael Koller
- Clinic for Transplantation Immunology and Nephrology, Basel University Hospital, Basel, Switzerland
| | - Simona Rossi
- Clinic for Transplantation Immunology and Nephrology, Basel University Hospital, Basel, Switzerland
| | - Vanessa Banz
- University Clinic for Visceral Surgery and Medicine, University Hospital Bern and University of Bern, Bern, Switzerland
| | - Bruno Schmied
- Department of General, Visceral, Endocrine and Transplantation Surgery, Cantonal Hospital St. Gallen, St. Gallen, Switzerland
| | - Lorenz Guerke
- Department of Vascular and Transplant Surgery, Basel University Hospital, Basel, Switzerland
| | - Maurice Matter
- Visceral Surgery Department, University Hospital of Lausanne (CHUV), Lausanne, Switzerland
| | - Olivier de Rougemont
- Department of Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland
| | - Marco Bonani
- Division of Nephrology, University Hospital Zurich, Zurich, Switzerland
| | - Déla Golshayan
- Transplantation Center, University Hospital of Lausanne (CHUV), Lausanne, Switzerland
| | - Aurelia Schnyder
- Clinic for Nephrology, Cantonal Hospital St. Gallen, St.Gallen, Switzerland
| | - Daniel Sidler
- Division of Nephrology and Hypertension, Inselspital, Bern University Hospital, Bern, Switzerland
| | - Fadi Haidar
- Division of Nephrology, Department of Medicine, University Hospital of Geneva, Geneva, Switzerland
| | - Stefan P Kuster
- Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich and University Zurich, Zurich, Switzerland
| | - Susanne Stampf
- Clinic for Transplantation Immunology and Nephrology, Basel University Hospital, Basel, Switzerland
| | - Nicolas J Mueller
- Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich and University Zurich, Zurich, Switzerland
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32
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Stoumpos S, Van Rhijn P, Mangion K, Thomson PC, Mark PB. Arteriovenous fistula for haemodialysis as a predictor of de novo heart failure in kidney transplant recipients. Clin Kidney J 2024; 17:sfae105. [PMID: 38737344 PMCID: PMC11087827 DOI: 10.1093/ckj/sfae105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Indexed: 05/14/2024] Open
Abstract
Background The haemodynamic effects of a functioning haemodialysis arteriovenous fistula (AVF) can cause or exacerbate heart failure (HF). We investigated whether the presence of an AVF at the time of kidney transplant (KT) is associated with de novo HF. Methods This was an observational cohort study including adult patients who received a KT in the West of Scotland between 2010 and 2020. We evaluated the risk and associations of pretransplant factors with de novo HF, alone and as a composite cardiovascular (CV) outcome (including non-fatal myocardial infarction, non-fatal stroke, de novo HF and CV death). Multivariable proportional hazards regression and sensitivity analyses were used to identify independent correlates of the outcomes. Results Among 1330 included patients, the incident rate of de novo HF after transplantation was 58/1000 person-years [95% confidence interval (CI) 50-67] in AVF patients (n = 716) compared with 33/1000 person-years (95% CI 27-41) in non-AVF patients (n = 614). De novo HF was associated with the presence of an AVF [adjusted hazard ratio (aHR) 2.14 (95% CI 1.40-3.26)], duration of dialysis [aHR 1.03/year increase (95% CI 1.01-1.04)], age at transplant [aHR 1.03/year increase (95% CI 1.02-1.05)], female sex [aHR 1.93 (95% CI 1.40-2.65)] and pretransplant diabetes [aHR 2.43 (95% CI 1.48-4.01)]. The presence of an AVF was also associated with the composite CV outcome [aHR 1.91 (95% CI 1.31-2.78)]. Conclusions The presence of an AVF may be an underrecognized modifiable predictor of de novo HF posttransplantation.
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Affiliation(s)
- Sokratis Stoumpos
- Renal and Transplant Unit, Queen Elizabeth University Hospital, Glasgow, UK
| | - Peter Van Rhijn
- Renal and Transplant Unit, Queen Elizabeth University Hospital, Glasgow, UK
| | - Kenneth Mangion
- School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK
| | - Peter C Thomson
- Renal and Transplant Unit, Queen Elizabeth University Hospital, Glasgow, UK
| | - Patrick B Mark
- Renal and Transplant Unit, Queen Elizabeth University Hospital, Glasgow, UK
- School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK
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33
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Pruett TL, Martin P, Gupta D. Outcomes of kidneys used for transplantation: an analysis of survival and function. FRONTIERS IN TRANSPLANTATION 2024; 3:1335999. [PMID: 38993770 PMCID: PMC11235350 DOI: 10.3389/frtra.2024.1335999] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Accepted: 02/19/2024] [Indexed: 07/13/2024]
Abstract
Introduction Kidney transplant recipients expect to survive the procedure with sufficient renal function for reliable dialysis freedom. Methods Transplant outcomes (survival and estimated renal function) were assessed after live and deceased donor transplantation from the US national database. Outcomes were stratified by age (donor and recipient) and donor type. Results Aggregate recipient outcomes were better transplanting living vs deceased donated kidneys. However, when stratified by the one-year renal function (within KDIGO CKD stage stratifications), surviving recipients had clinically similar dialysis-freedom, irrespective of donor type or age. The major outcome differences for recipients of age-stratified live and deceased kidneys was 1) the increasing frequency of one-year graft failures and 2) the increasing likelihood of severely limited renal function (CKD 4/5) with advancing donor age. Over 30% of recipients of deceased kidneys >65 years had either one-year graft failure or severely limited renal function contrasted to less than 15% of recipients of live kidneys aged >65 years. Conclusions Evolving techniques to reduce adverse events after urgent vs elective procedures, plus improved transplant outcome predictability with increased-age deceased donor kidneys using advanced predictive analytics (using age-stratified live kidney transplantation outcomes as a relevant reference point) should facilitate similar kidney transplant outcomes, irrespective of donor type.
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Affiliation(s)
- Timothy L. Pruett
- Division of Transplantation, University of Minnesota School of Medicine, Minneapolis, MN, United States
| | - Paola Martin
- ODT, Kelley School of Business, Indiana University, Bloomington, IN, United States
| | - Diwakar Gupta
- IROM, The McCombs School of Business at University of Texas (Austin), Austin, TX, United States
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Yasir MB, Man RK, Gogikar A, Nanda A, Niharika Janga LS, Sambe HG, Mohamed L. A Systematic Review Exploring the Impact of Arteriovenous Fistula Ligature on High-Output Heart Failure in Renal Transplant Recipients. Ann Vasc Surg 2024; 100:67-80. [PMID: 38122973 DOI: 10.1016/j.avsg.2023.10.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Revised: 10/08/2023] [Accepted: 10/11/2023] [Indexed: 12/23/2023]
Abstract
BACKGROUND Cardiovascular disease is the most common cause of death in renal transplant recipients (RTrs). High-output heart failure (HoHF) is a classic problem of RTrs with patent arteriovenous fistulae (AVF). Central to the entire discipline of transplant nephrology is the ligation of AVF in RTrs, with a patent AVF presenting with signs and symptoms of HoHF. AVF ligation has long been a topic of great interest in this population. To date, little attention has been paid to the effects of arteriovenous graft ligation on HoHF. This study systematically reviews the data for AVF ligation, aiming to provide its impact on HoHF in RTrs. METHODS The present study adopts the Preferred Reporting Items for Systematic Reviews and Meta-analysis 2020 guidelines. Published studies were identified using a search strategy in PubMed, Scopus, PubMed Central, Science Direct, and Medline. The primary inclusion criterion for this review was RTrs with a patent AVF who exhibited clinical or imaging findings of HoHF. Articles dating back to the last decade that involved the human species were included in our review, and the search was restricted to the English language. Studies involving both male and female genders and those describing the adult population (aged > 19 years) were also a part of our inclusion criteria. RESULTS After applying eligibility criteria, our electronic search yielded 1,461 articles. A total of 16 studies that involved 18,735 subjects were included in our review, which comprised 6 cohort studies, 4 case reports, 2 randomized control trials, 2 narrative reviews, 1 meta-analysis, and 1 case series. While the risk of bias of the narrative reviews was low, 1 of the randomized control trials had some overall concerns. The meta-analysis included in our review had moderate risk of bias, while 4 of the 6 cohort studies were of good quality. All of the case reports and series included in our review were of good quality. Of the 12 studies that reported genders, 10,949 were male and 6,416 were female. There was a notable reduction in left ventricular mass, left ventricular mass index, left ventricular end diastolic dimension, cardiac output, velocity index, and systemic vascular resistance index upon AVF ligation. CONCLUSIONS A complete resolution of the clinical signs and symptoms of HoHF can be anticipated after AVF ligation in RTrs. Clinicians should always be on the lookout for signs and symptoms of cardiovascular decompensation in asymptomatic RTrs.
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Affiliation(s)
- Mohamed B Yasir
- Division of Research, California Institute of Behavioral Neurosciences & Psychology, Fairfield, CA.
| | - Ruzhual Kaur Man
- Division of Research, California Institute of Behavioral Neurosciences & Psychology, Fairfield, CA
| | - Amaresh Gogikar
- Division of Research, California Institute of Behavioral Neurosciences & Psychology, Fairfield, CA
| | - Ankita Nanda
- Division of Research, California Institute of Behavioral Neurosciences & Psychology, Fairfield, CA
| | | | - Hembashima G Sambe
- Division of Research, California Institute of Behavioral Neurosciences & Psychology, Fairfield, CA
| | - Lubna Mohamed
- Division of Research, California Institute of Behavioral Neurosciences & Psychology, Fairfield, CA
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Helve S, Helanterä I, Laine M, Nieminen T, Finne P, Helve J. Trends and Specific Causes of Cardiovascular Mortality after Kidney Transplantation in Finland. Clin J Am Soc Nephrol 2024; 19:355-363. [PMID: 37962909 PMCID: PMC10937022 DOI: 10.2215/cjn.0000000000000360] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Accepted: 11/08/2023] [Indexed: 11/15/2023]
Abstract
BACKGROUND Cardiovascular diseases are an important cause of mortality in patients who have undergone kidney transplantation, but the knowledge on trends of cardiovascular mortality and specific causes of cardiovascular death among these patients is scarce. METHODS Our aim was to compare the cardiovascular mortality rates after kidney transplantation in Finland between 1990-1999, 2000-2009, and 2010-2019 using data from the Finnish Registry for Kidney Diseases. We analyzed 1-year and long-term cardiovascular mortality rates as well as the specific causes of cardiovascular death and the trends in them. RESULTS In total, 4946 patients underwent first kidney transplantation in 1990-2019. During the follow-up time (median 8.3 years, interquartile range 4.0-14.5), there were 1392 deaths, of which 582 were cardiovascular deaths. In an unadjusted Cox regression model, the risk of long-term cardiovascular mortality was similar in the different periods. However, when adjusted for age, sex, duration of dialysis, and cause of kidney disease, the long-term cardiovascular mortality risk was significantly lower in 2000-2009 and 2010-2019 (hazard ratio 0.60 [95% confidence interval, 0.49 to 0.73] and hazard ratio 0.51 [95% confidence interval, 0.39 to 0.66], respectively) compared with 1990-1999. The results were similar regarding 1-year cardiovascular mortality. The distribution of different causes of cardiovascular death remained unchanged during the study period, with coronary artery disease accounting for 47% of deaths. During the first year after transplantation, pulmonary embolisms and arrhythmias were more common than in the long term. CONCLUSIONS Cardiovascular disease remained the most common cause of death in kidney transplant recipients, but adjusted cardiovascular mortality risk has decreased significantly during the past three decades. Coronary artery disease was the most frequent cause of cardiovascular death, and the proportion of coronary artery disease-related cardiovascular deaths increased after the first year after transplantation.
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Affiliation(s)
- Salla Helve
- Department of Internal Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Ilkka Helanterä
- Department of Transplantation and Liver Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Mika Laine
- Heart and Lung Center, Helsinki University and Helsinki University Hospital, Helsinki, Finland
| | - Tuomo Nieminen
- The Wellbeing Services County of Päijät-Häme, Lahti, Finland
| | - Patrik Finne
- Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Jaakko Helve
- Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Finnish Registry for Kidney Diseases, Helsinki, Finland
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Jørgensen IF, Muse VP, Aguayo-Orozco A, Brunak S, Sørensen SS. Stratification of Kidney Transplant Recipients Into Five Subgroups Based on Temporal Disease Trajectories. Transplant Direct 2024; 10:e1576. [PMID: 38274475 PMCID: PMC10810574 DOI: 10.1097/txd.0000000000001576] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Revised: 11/02/2023] [Accepted: 11/28/2023] [Indexed: 01/27/2024] Open
Abstract
Background Kidney transplantation is the treatment of choice for patients with end-stage renal disease. Considerable clinical research has focused on improving graft survival and an increasing number of kidney recipients die with a functioning graft. There is a need to improve patient survival and to better understand the individualized risk of comorbidities and complications. Here, we developed a method to stratify recipients into similar subgroups based on previous comorbidities and subsequently identify complications and for a subpopulation, laboratory test values associated with survival. Methods First, we identified significant disease patterns based on all hospital diagnoses from the Danish National Patient Registry for 5752 kidney transplant recipients from 1977 to 2018. Using hierarchical clustering, these longitudinal patterns of diseases segregate into 3 main clusters of glomerulonephritis, hypertension, and diabetes. As some recipients are diagnosed with diseases from >1 cluster, recipients are further stratified into 5 more fine-grained trajectory subgroups for which survival, stratified complication patterns as well as laboratory test values are analyzed. Results The study replicated known associations indicating that diabetes and low levels of albumin are associated with worse survival when investigating all recipients. However, stratification of recipients by trajectory subgroup showed additional associations. For recipients with glomerulonephritis, higher levels of basophils are significantly associated with poor survival, and these patients are more often diagnosed with bacterial infections. Additional associations were also found. Conclusions This study demonstrates that disease trajectories can confirm known comorbidities and furthermore stratify kidney transplant recipients into clinical subgroups in which we can characterize stratified risk factors. We hope to motivate future studies to stratify recipients into more fine-grained, homogenous subgroups to better discover associations relevant for the individual patient and thereby enable more personalized disease-management and improve long-term outcomes and survival.
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Affiliation(s)
- Isabella F. Jørgensen
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen N, Denmark
| | - Victorine P. Muse
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen N, Denmark
| | - Alejandro Aguayo-Orozco
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen N, Denmark
| | - Søren Brunak
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen N, Denmark
| | - Søren S. Sørensen
- Department of Nephrology, Rigshospitalet, Copenhagen University Hospital, Copenhagen Ø, Denmark
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Murakami N, Reich AJ, He K, Gelfand SL, Leiter RE, Sciacca K, Adler JT, Lu E, Ong SC, Concepcion BP, Singh N, Murad H, Anand P, Ramer SJ, Dadhania DM, Lentine KL, Lakin JR, Alhamad T. Kidney Transplant Clinicians' Perceptions of Palliative Care for Patients With Failing Allografts in the US: A Mixed Methods Study. Am J Kidney Dis 2024; 83:173-182.e1. [PMID: 37726050 PMCID: PMC11360225 DOI: 10.1053/j.ajkd.2023.07.013] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Revised: 06/03/2023] [Accepted: 07/09/2023] [Indexed: 09/21/2023]
Abstract
RATIONALE & OBJECTIVE Kidney transplant patients with failing allografts have a physical and psychological symptom burden as well as high morbidity and mortality. Palliative care is underutilized in this vulnerable population. We described kidney transplant clinicians' perceptions of palliative care to delineate their perceived barriers to and facilitators of providing palliative care to this population. STUDY DESIGN National explanatory sequential mixed methods study including an online survey and semistructured interviews. SETTING & PARTICIPANTS Kidney transplant clinicians in the United States surveyed and interviewed from October 2021 to March 2022. ANALYTICAL APPROACH Descriptive summary of survey responses, thematic analysis of qualitative interviews, and mixed methods integration of data. RESULTS A total of 149 clinicians completed the survey, and 19 completed the subsequent interviews. Over 90% of respondents agreed that palliative care can be helpful for patients with a failing kidney allograft. However, 46% of respondents disagreed that all patients with failing allografts benefit from palliative care, and two-thirds thought that patients would not want serious illness conversations. More than 90% of clinicians expressed concern that transplant patients and caregivers would feel scared or anxious if offered palliative care. The interviews identified three main themes: (1) transplant clinicians' unique sense of personal and professional responsibility was a barrier to palliative care engagement, (2) clinicians' uncertainty regarding the timing of palliative care collaboration would lead to delayed referral, and (3) clinicians felt challenged by factors related to patients' cultural backgrounds and identities, such as language differences. Many comments reflected an unfamiliarity with the broad scope of palliative care beyond end-of-life care. LIMITATIONS Potential selection bias. CONCLUSIONS Our study suggests that multiple barriers related to patients, clinicians, health systems, and health policies may pose challenges to the delivery of palliative care for patients with failing kidney transplants. This study illustrates the urgent need for ongoing efforts to optimize palliative care delivery models dedicated to kidney transplant patients, their families, and the clinicians who serve them. PLAIN-LANGUAGE SUMMARY Kidney transplant patients experience physical and psychological suffering in the context of their illnesses that may be amenable to palliative care. However, palliative care is often underutilized in this population. In this mixed-methods study, we surveyed 149 clinicians across the United States, and 19 of them completed semistructured interviews. Our study results demonstrate that several patient, clinician, system, and policy factors need to be addressed to improve palliative care delivery to this vulnerable population.
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Affiliation(s)
- Naoka Murakami
- Division of Renal Medicine, Brigham and Women's Hospital, Boston, Massachusetts
| | - Amanda J Reich
- Center for Surgery and Public Health, Brigham and Women's Hospital, Boston, Massachusetts
| | - Katherine He
- Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts
| | - Samantha L Gelfand
- Division of Renal Medicine, Brigham and Women's Hospital, Boston, Massachusetts; Department of Psychosocial Oncology and Palliative Care, Dana-Farber Cancer Institute, Boston, Massachusetts
| | - Richard E Leiter
- Department of Psychosocial Oncology and Palliative Care, Dana-Farber Cancer Institute, Boston, Massachusetts
| | - Kate Sciacca
- Department of Psychosocial Oncology and Palliative Care, Dana-Farber Cancer Institute, Boston, Massachusetts
| | - Joel T Adler
- Department of Surgery, Dell Medical School, University of Texas at Austin, Austin, Texas
| | - Emily Lu
- Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Song C Ong
- Division of Nephrology, University of Alabama at Birmingham, Birmingham, Alabama
| | - Beatrice P Concepcion
- Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Neeraj Singh
- Willis Knighton Health System, Shreveport, Louisiana
| | - Haris Murad
- Department of Medicine, Aga Khan University, Karachi, Pakistan
| | - Prince Anand
- Medical University of South Carolina, Greenville, South Carolina
| | | | | | - Krista L Lentine
- Saint Louis University Transplant Center, SSM-Saint Louis University Hospital, St Louis, Missouri
| | - Joshua R Lakin
- Department of Psychosocial Oncology and Palliative Care, Dana-Farber Cancer Institute, Boston, Massachusetts.
| | - Tarek Alhamad
- Division of Nephrology, Washington University in St. Louis, St. Louis, Missouri.
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Fang Y, Hamm JJ, den Hartog FP, Kimenai HJ, de Bruin RW, Minnee RC. Safety and efficacy of kidney transplantation in patients with aortoiliac stenosis: a retrospective cohort study. Int J Surg 2024; 110:992-999. [PMID: 38016127 PMCID: PMC10871560 DOI: 10.1097/js9.0000000000000926] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Accepted: 11/09/2023] [Indexed: 11/30/2023]
Abstract
BACKGROUND The impact of aortoiliac occlusive disease on kidney transplantation remains unclear. This study aims to investigate the clinical outcomes of kidney transplant patients with aortoiliac atherosclerotic stenosis. METHODS Retrospective data from our transplant center were used to identify patients undergoing kidney transplantation between January 2010 and December 2020. Aortoiliac atherosclerotic stenosis was screened and stratified by the Trans-Atlantic Inter-Society Consensus (TASC) II classification. The primary outcome was patient survival. Secondary outcomes were 90-day mortality, death-censored graft survival, graft function, and arterial complications. Propensity score matching was used to match all patients in the stenosis group with patients without stenosis sharing similar characteristics. RESULTS The analysis included 655 patients, 524 without stenosis and 131 with aortoiliac stenosis (95 with TASC A/B stenosis and 36 with TASC C/D stenosis). Recipient age [median (IQR), 66 (60-70) vs. 66 (59-71) years; P =0.47], sex [male: 87 (66%) vs. 355 (68%), P =0.85], and comorbidities were comparable between the stenosis and no-stenosis groups. Forty-six (35%) patients with stenosis were symptomatic. Patient survival was significantly lower in the stenosis group compared with the no-stenosis group (TASC A/B: 30.6% vs. no-stenosis: 44.1%, P =0.013; TASC C/D: 11.4% vs. no-stenosis: 44.1%, P <0.001). The incidence rates of artery dissection, lower extremity ischemia, and acute thrombosis were significantly higher in the stenosis group ( P <0.001). However, death-censored graft survival (TASC A/B: 73.6% vs. no-stenosis: 72.9%, P =0.62; TASC C/D: 58.1% vs. no-stenosis: 72.9%, P =0.16) and graft function were comparable between the groups. CONCLUSIONS Aortoiliac atherosclerotic stenosis significantly impacts patient survival but not graft survival. Our analyses suggest that patients with TASC A/B stenosis have prolonged survival and enhanced quality of life through kidney transplantation. However, for patients with TASC C/D stenosis, kidney transplantation improves quality of life without bringing survival benefits.
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Affiliation(s)
- Yitian Fang
- Erasmus MC Transplant Institute, Department of Surgery, Division of HPB and Transplant Surgery
| | - Julie J.M. Hamm
- Erasmus MC Transplant Institute, Department of Surgery, Division of HPB and Transplant Surgery
| | | | | | - Ron W.F. de Bruin
- Erasmus MC Transplant Institute, Department of Surgery, Division of HPB and Transplant Surgery
| | - Robert C. Minnee
- Erasmus MC Transplant Institute, Department of Surgery, Division of HPB and Transplant Surgery
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Choi MC, Kim DG, Yim SH, Kim HJ, Kim HW, Yang J, Kim BS, Huh KH, Kim MS, Lee J. Creatinine-cystatin C ratio and death with a functioning graft in kidney transplant recipients. Sci Rep 2024; 14:1966. [PMID: 38263396 PMCID: PMC10806062 DOI: 10.1038/s41598-024-52649-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Accepted: 01/22/2024] [Indexed: 01/25/2024] Open
Abstract
Death with a functioning graft is important cause of graft loss after kidney transplantation. However, little is known about factors predicting death with a functioning graft among kidney transplant recipients. In this study, we evaluated the association between post-transplant creatinine-cystatin C ratio and death with a functioning graft in 1592 kidney transplant recipients. We divided the patients into tertiles based on sex-specific creatinine-cystatin C ratio. Among the 1592 recipients, 39.5% were female, and 86.1% underwent living-donor kidney transplantation. The cut-off value for the lowest creatinine-cystatin C ratio tertile was 0.86 in males and 0.73 in females. The lowest tertile had a significantly lower 5-year patient survival rate and was independently associated with death with a functioning graft (adjusted hazard ratio 2.574, 95% confidence interval 1.339-4.950, P < 0.001). Infection was the most common cause of death in the lowest tertile group, accounting for 62% of deaths. A low creatinine-cystatin C ratio was significantly associated with an increased risk of death with a functioning graft after kidney transplantation.
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Affiliation(s)
- Mun Chae Choi
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
- The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Deok Gie Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
- The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Seung Hyuk Yim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
- The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hyun Jeong Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
- The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hyoung Woo Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jaeseok Yang
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Beom Seok Kim
- The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Republic of Korea
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Kyu Ha Huh
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
- The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Myoung Soo Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
- The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Juhan Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea.
- The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Republic of Korea.
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DeLaura I, Zikos J, Anwar IJ, Yoon J, Ladowski J, Jackson A, Van Rompay K, Magnani D, Knechtle SJ, Kwun J. The impact of IdeS (imlifidase) on allo-specific, xeno-reactive, and protective antibodies in a sensitized rhesus macaque model. Xenotransplantation 2024; 31:e12833. [PMID: 37864433 PMCID: PMC10999173 DOI: 10.1111/xen.12833] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Revised: 08/17/2023] [Accepted: 10/13/2023] [Indexed: 10/22/2023]
Abstract
BACKGROUND Highly sensitized patients face many barriers to kidney transplantation, including higher rates of antibody-mediated rejection after HLA-incompatible transplant. IdeS, an endopeptidase that cleaves IgG nonspecifically, has been trialed as desensitization prior to kidney transplant, and successfully cleaves donor-specific antibody (DSA), albeit with rebound. METHODS IdeS was generated and tested (2 mg/kg, IV) in two naïve and four allosensitized nonhuman primates (NHP). Peripheral blood samples were collected at regular intervals following IdeS administration. Total IgG, total IgM, and anti-CMV antibodies were quantified with ELISA, and donor-specific antibody (DSA) and anti-pig antibodies were evaluated using flow cytometric crossmatch. B cell populations were assessed using flow cytometry. RESULTS IdeS successfully cleaved rhesus IgG in vitro. In allosensitized NHP, robust reduction of total, DSA, anti-pig, and anti-CMV IgG was observed within one day following IdeS administration. Rapid rebound of all IgG antibody populations was observed, with antibody levels returning to baseline around day 14 post-infusion. Total IgM level was not affected by IdeS. Interestingly, a comparable reduction in antibody populations was observed after the second dose of IdeS. However, we have not observed any significant modulation of B cell subpopulations after IdeS. CONCLUSIONS This study evaluated efficacy of IdeS in the allosensitized NHP in IgG with various specificities, mirroring antibody kinetics in human patients. The efficacy of IdeS on preexisting anti-pig antibodies may be useful in clinical xenotransplantation. However, given the limitation of IdeS on its durability as a monotherapy, optimization of IdeS with other agents targeting the humoral response is further needed.
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Affiliation(s)
- Isabel DeLaura
- Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710
| | - Joanna Zikos
- MassBiologics of University of Massachusetts Medical School, Boston, MA, 02126, USA
| | - Imran J. Anwar
- Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710
| | - Janghoon Yoon
- Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710
| | - Joseph Ladowski
- Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710
| | - Annette Jackson
- Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710
| | - Koen Van Rompay
- California National Primate Research Center, University of California, Davis, CA 95616, USA
| | - Diogo Magnani
- MassBiologics of University of Massachusetts Medical School, Boston, MA, 02126, USA
| | - Stuart J. Knechtle
- Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710
| | - Jean Kwun
- Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710
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Massicotte-Azarniouch D, Noel JA, Knoll GA. Epidemiology of Cancer in Kidney Transplant Recipients. Semin Nephrol 2024; 44:151494. [PMID: 38538455 DOI: 10.1016/j.semnephrol.2024.151494] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/30/2024]
Abstract
Kidney transplantation is the ideal treatment modality for patients with end-stage kidney disease, with excellent outcomes post-transplant compared with dialysis. However, kidney transplant recipients are at increased risk of infections and cancer because of the need for immunosuppression. Kidney transplant recipients have approximately two to three times greater risk of developing cancer than the general population, and cancer is a major contributor to morbidity and mortality. Most of the increased risk is driven by viral-mediated cancers such as post-transplant lymphoproliferative disorder, anogenital cancers, and Kaposi sarcoma. Nonmelanoma skin cancer is the most frequent type of cancer in kidney transplant recipients, likely due to an interaction between ultraviolet radiation exposure and decreased immune surveillance. Occurrence of the more common types of solid organ cancers seen in the general population, such as breast, prostate, lung, and colorectal cancers, is not, or is only mildly, increased post-transplant. Clinical care and future research should focus on prevention and on improving outcomes for important immunosuppression-related malignancies, and treatment options for other cancers occurring in the transplant setting.
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Affiliation(s)
- David Massicotte-Azarniouch
- Division of Nephrology, Department of Medicine and Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Canada
| | - J Ariana Noel
- Department of Medicine, University of Ottawa, Ottawa, Canada
| | - Greg A Knoll
- Division of Nephrology, Department of Medicine and Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Canada.
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Perez-Gutierrez A, McGill RL, Juengel B, Bachul PJ, Danz DN, Josephson M, Chung BB, Nguyen A, Fung JJ, Barth RN, Becker YT. The Seattle Heart Failure Model in Kidney Transplant Recipients. J Clin Med 2023; 12:7614. [PMID: 38137683 PMCID: PMC10743453 DOI: 10.3390/jcm12247614] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2023] [Revised: 12/01/2023] [Accepted: 12/06/2023] [Indexed: 12/24/2023] Open
Abstract
Cardiovascular disease is the leading cause of mortality following kidney transplantation. Heart failure affects 17-21% of patients with chronic kidney disease and increases along with time receiving dialysis. The Seattle Heart Failure Model (SHFM) is a validated mortality risk model for heart failure patients that incorporates clinical, therapeutic, and laboratory parameters but does not include measures of kidney function. We applied the SHFM to patients with end-stage renal disease (ESRD) who were being evaluated for kidney transplantation to determine if the model was associated with post-transplant mortality. This retrospective single-center study analyzed survival among 360 adult deceased-donor kidney transplant recipients. Cox regression was used to model post-transplant patient survival. Our findings indicated that a 1.0-point increase in the adapted SHFM score was significantly associated with post-transplant mortality (HR 1.76, 95% CI = 1.10-2.83, p = 0.02), independently of the Kidney Donor Profile Index and Estimated Post-Transplant Survival. Individual covariates of the SHFM were evaluated in univariate analyses, and age, sodium, cholesterol, and lymphocyte count were significantly related to mortality. This study provides preliminary evidence that an adapted SHFM score could be a useful tool in evaluating mortality risk post-transplant in patients with ESRD.
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Affiliation(s)
| | - Rita L. McGill
- Section of Nephrology, Department of Medicine, University of Chicago, Chicago, IL 60637, USA
| | - Braden Juengel
- Department of Surgery, Transplant Institute, University of Chicago, Chicago, IL 60637, USA
| | - Piotr J. Bachul
- Department of Surgery, Transplant Institute, University of Chicago, Chicago, IL 60637, USA
| | - David N. Danz
- Department of Economics, University of Pittsburgh, Pittsburgh, PA 15260, USA
| | - Michelle Josephson
- Section of Nephrology, Department of Medicine, University of Chicago, Chicago, IL 60637, USA
| | - Ben B. Chung
- Section of Cardiology, Department of Medicine, University of Chicago, Chicago, IL 60637, USA
| | - Ann Nguyen
- Section of Cardiology, Department of Medicine, University of Chicago, Chicago, IL 60637, USA
| | - John J. Fung
- Department of Surgery, Transplant Institute, University of Chicago, Chicago, IL 60637, USA
| | - Rolf N. Barth
- Department of Surgery, Transplant Institute, University of Chicago, Chicago, IL 60637, USA
| | - Yolanda T. Becker
- Department of Surgery, Transplant Institute, University of Chicago, Chicago, IL 60637, USA
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Xagas E, Sarafidis P, Iatridi F, Theodorakopoulou MP, Pella E, Korogiannou M, Argyris A, Protogerou A, Boletis IN, Marinaki S. Kidney transplantation and kidney donation do not affect short-term blood pressure variability. Blood Press 2023; 32:2181640. [PMID: 36814377 DOI: 10.1080/08037051.2023.2181640] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/24/2023]
Abstract
PURPOSE Blood pressure variability (BPV) is an independent cardiovascular risk factor in CKD. Kidney transplantation (KTx) is associated with improved BP levels for kidney transplant recipient (KTRs), without evoking significant changes in donors. The aim of this study was to assess the short- and mid-time effects of KTx and donation on short-term BPV in KTRs and their respective living kidney donors. MATERIALS AND METHODS Forty KTRs and their respective donors were evaluated with 24-h ABPM (Mobil-O-Graph-NG) at baseline (1 month before), 3-months and 12-months after KTx. Standard-deviation (SD), weighted-SD (wSD), coefficient-of-variation (CV), average-real-variability (ARV) and variability independent of mean (VIM) for SBP/DBP were calculated with validated formulas. RESULTS All 24-h systolic and diastolic BPV indexes studied did not change significantly from baseline to 3-month (SBP-wSD: 12.8 ± 3.0 vs 13.2 ± 3.4 mmHg, p = 0.608; SBP-ARV: 10.3 ± 2.4 vs 10.8 ± 2.6 mmHg, p = 0.463) and 12-month evaluation (SBP-wSD 12.8 ± 3.0 vs 12.1 ± 2.8; p = 0.424 and SBP-ARV: 10.3 ± 2.4 vs 10.2 ± 2.5; p = 0.615) after kidney transplantation in the KTRs.In kidney donors, all 24-h systolic BPV indices displayed a trend towards higher values at 3 months compared to baseline, but without reaching statistical significance (SBP-wSD: 12.2 ± 2.8 vs 13.6 ± 4.2 mmHg, p = 0.107 and SBP-ARV: 10.1 ± 2.1 vs 11.2 ± 3.1 mmHg, p = 0.099), the levels of 24-h systolic SBP indices at 12-months were almost identical to baseline values. 24-h diastolic BPV indices at 3-month and 12-month evaluation were similar to baseline. CONCLUSION Short-term BPV did not change significantly 3 and 12 months after kidney transplantation/donation neither in KTRs nor in living kidney donors. Longitudinal studies examining associations of BPV with adverse outcomes in these individuals are needed.
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Affiliation(s)
- Efstathios Xagas
- Clinic of Nephrology and Renal Transplantation, Laiko General Hospital, Medical School of Athens, National and Kapodistrian University of Athens, Athens, Greece
| | - Pantelis Sarafidis
- Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Fotini Iatridi
- Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Marieta P Theodorakopoulou
- Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Eva Pella
- Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Maria Korogiannou
- Clinic of Nephrology and Renal Transplantation, Laiko General Hospital, Medical School of Athens, National and Kapodistrian University of Athens, Athens, Greece
| | - Antonis Argyris
- Cardiovascular Prevention & Research Unit, Clinic & Laboratory of Pathophysiology, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Athanase Protogerou
- Cardiovascular Prevention & Research Unit, Clinic & Laboratory of Pathophysiology, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Ioannis N Boletis
- Clinic of Nephrology and Renal Transplantation, Laiko General Hospital, Medical School of Athens, National and Kapodistrian University of Athens, Athens, Greece
| | - Smaragdi Marinaki
- Clinic of Nephrology and Renal Transplantation, Laiko General Hospital, Medical School of Athens, National and Kapodistrian University of Athens, Athens, Greece
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de-Miguel-Yanes JM, Lopez-de-Andres A, Jimenez-Garcia R, Zamorano-Leon JJ, Carabantes-Alarcon D, Hernández-Barrera V, De-Miguel-Diez J, Carricondo F, Romero-Gomez B, Cuadrado-Corrales N. Observational Study of the Association between Atrial Fibrillation and In-Hospital Mortality during Hospitalization for Solid Organ Transplants in Spain from 2004 to 2021. J Clin Med 2023; 12:7056. [PMID: 38002669 PMCID: PMC10671923 DOI: 10.3390/jcm12227056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Revised: 11/07/2023] [Accepted: 11/10/2023] [Indexed: 11/26/2023] Open
Abstract
(1) Background: We analyzed the association between atrial fibrillation or atrial flutter (AF) and in-hospital mortality (IHM) among patients who underwent solid organ transplants in Spain from 2004 to 2021. (2) Methods: We gathered information from all hospital admissions for lung, liver, kidney, and heart transplants. (3) Results: A total of 71,827 transplants were analyzed (4598 lung transplants; 18,127 liver transplants; 45,262 kidney transplants; and 4734 heart transplants). One third of these were for women. Overall, the prevalence of AF was 6.8% and increased from 5.3% in 2004-2009 to 8.6% in 2016-2021. The highest prevalence of AF was found for heart transplants (24.0%), followed by lung transplants (14.7%). The rates for kidney and liver transplants were 5.3% and 4.1%, respectively. The AF code increased over time for all of the transplants analyzed (p < 0.001). The patients' IHM decreased significantly from 2004-2009 to 2016-2021 for all types of transplants. AF was associated with a higher IHM for all of the types of transplants analyzed, except for heart transplants. (4) Conclusions: The prevalence of AF among patients admitted for solid organ transplants was highest for those who underwent heart transplants. The mortality rate during the patients' admission for lung, liver, kidney, or heart transplants decreased over time. AF was independently associated with a higher risk of dying in the hospital for those who underwent lung, liver, or kidney transplants.
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Affiliation(s)
- José M de-Miguel-Yanes
- Internal Medicine Department, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Universidad Complutense de Madrid, 28040 Madrid, Spain;
| | - Ana Lopez-de-Andres
- Department of Public Health and Maternal & Child Health, Faculty of Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain; (R.J.-G.); (J.J.Z.-L.); (D.C.-A.); (N.C.-C.)
| | - Rodrigo Jimenez-Garcia
- Department of Public Health and Maternal & Child Health, Faculty of Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain; (R.J.-G.); (J.J.Z.-L.); (D.C.-A.); (N.C.-C.)
| | - José J Zamorano-Leon
- Department of Public Health and Maternal & Child Health, Faculty of Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain; (R.J.-G.); (J.J.Z.-L.); (D.C.-A.); (N.C.-C.)
| | - David Carabantes-Alarcon
- Department of Public Health and Maternal & Child Health, Faculty of Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain; (R.J.-G.); (J.J.Z.-L.); (D.C.-A.); (N.C.-C.)
| | - Valentín Hernández-Barrera
- Preventive Medicine and Public Health Teaching and Research Unit, Health Sciences Faculty, Rey Juan Carlos University, Alcorcón, 28922 Madrid, Spain;
| | - Javier De-Miguel-Diez
- Respiratory Department, Hospital General Universitario Gregorio Marañón, Facultad de Medicina, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Universidad Complutense de Madrid, 28009 Madrid, Spain;
| | - Francisco Carricondo
- Laboratory of Neurobiology of Hearing (UCM 910915), Ophthalmology and Otorhinolaryngology, Department of Immunology, Faculty of Medicine, University Complutense, IdISSC, 28040 Madrid, Spain; (F.C.); (B.R.-G.)
| | - Barbara Romero-Gomez
- Laboratory of Neurobiology of Hearing (UCM 910915), Ophthalmology and Otorhinolaryngology, Department of Immunology, Faculty of Medicine, University Complutense, IdISSC, 28040 Madrid, Spain; (F.C.); (B.R.-G.)
| | - Natividad Cuadrado-Corrales
- Department of Public Health and Maternal & Child Health, Faculty of Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain; (R.J.-G.); (J.J.Z.-L.); (D.C.-A.); (N.C.-C.)
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Han HS, Lubetzky ML. Immune monitoring of allograft status in kidney transplant recipients. FRONTIERS IN NEPHROLOGY 2023; 3:1293907. [PMID: 38022723 PMCID: PMC10663942 DOI: 10.3389/fneph.2023.1293907] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Accepted: 10/24/2023] [Indexed: 12/01/2023]
Abstract
Kidney transplant patients require careful management of immunosuppression to avoid rejection while minimizing the risk of infection and malignancy for the best long-term outcome. The gold standard for monitoring allograft status and immunosuppression adequacy is a kidney biopsy, but this is invasive and costly. Conventional methods of allograft monitoring, such as serum creatinine level, are non-specific. Although they alert physicians to the need to evaluate graft dysfunction, by the time there is a clinical abnormality, allograft damage may have already occurred. The development of novel and non-invasive methods of evaluating allograft status are important to improving graft outcomes. This review summarizes the available conventional and novel methods for monitoring allograft status after kidney transplant. Novel and less invasive methods include gene expression, cell-free DNA, urinary biomarkers, and the use of artificial intelligence. The optimal method to manage patients after kidney transplant is still being investigated. The development of less invasive methods to assess allograft function has the potential to improve patient outcomes and allow for a more personalized approach to immunosuppression management.
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Affiliation(s)
- Hwarang S. Han
- Division of Nephrology, Department of Internal Medicine, Dell Medical School, University of Texas at Austin, Austin, TX, United States
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Cieślik A, Burban A, Gniewkiewicz M, Gozdowska J, Dęborska-Materkowska D, Perkowska-Ptasinska A, Kosieradzki M, Durlik M. The Importance of 1-Year Protocol Biopsy in the Long-Term Prognosis of Kidney Transplants-5-Years Follow-Up. Transplant Proc 2023; 55:2053-2057. [PMID: 37778932 DOI: 10.1016/j.transproceed.2023.08.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Accepted: 08/01/2023] [Indexed: 10/03/2023]
Abstract
BACKGROUND Protocol biopsies are performed to detect subclinical pathologies that may lead to future graft dysfunction. However, they are not routinely performed interventions in every transplant center. There is no established regimen for performing them. PURPOSE The study aimed to evaluate if protocol biopsies can improve long-term patient outcomes after detecting early disorders and modifying treatment. MATERIAL AND METHODS Our observational study included 61 patients who underwent protocol biopsy 12 months after the transplantation. Based on the biopsy results, patients with abnormal histologic material (n = 37) were divided into 3 study groups as follows: patients with mild inflammatory lesions (n = 21), patients with interstitial fibrosis and tubular atrophy (IFTA) grade II to III (n = 12), and patients with BK virus nephropathy (n = 4). The control group (n = 24) included kidney recipients with IFTA 0 to I grade. Outcomes after 5-year follow-up were evaluated. RESULTS Five years after the biopsy, patients in the control group had stable graft function (5-year change in serum creatinine was -0.09 mg/dL). An increase in serum creatinine levels was observed in patients with IFTA II to III compared with the control group (0.14 mg/dL, P = .04). Immunosuppressive treatment was modified in the group with mild inflammatory changes and in the BKV group after the biopsy result. In the group with mild inflammatory lesions, renal function was stable (change of serum creatinine was -0.01 mg/dL, P = .51). In the BKV nephropathy group, there was a significant reduction in serum creatine levels (-0.48 mg/dL, P = .016). The analysis showed no diagnostic value for serum creatinine concentration (95% CI 0.49-0.78, P = .08). CONCLUSIONS Protocol biopsies are useful for detecting early pathologies and preventing allograft failure. They greatly benefit patients with detectable pathology that can be treated or in whom therapy modification is possible.
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Affiliation(s)
- Aleksandra Cieślik
- Department of Transplantation Medicine, Nephrology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland
| | - Anna Burban
- Department of Transplantation Medicine, Nephrology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland
| | - Michał Gniewkiewicz
- Department of Transplantation Medicine, Nephrology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland
| | - Jolanta Gozdowska
- Department of Transplantation Medicine, Nephrology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland.
| | - Dominika Dęborska-Materkowska
- Department of Transplantation Medicine, Nephrology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland
| | | | - Maciej Kosieradzki
- Department of General and Transplantation Surgery, The Medical University of Warsaw, Warsaw, Poland
| | - Magdalena Durlik
- Department of Transplantation Medicine, Nephrology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland
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Arabi Z, Tawhari MH, Al Rajih HS, Youssouf TM, Abdulgadir MY. Findings of Cardiovascular Workup of Kidney Transplant Candidates: A Retrospective Study of a Single-Center in Saudi Arabia. Int J Nephrol 2023; 2023:4653069. [PMID: 37854308 PMCID: PMC10581843 DOI: 10.1155/2023/4653069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Revised: 09/20/2023] [Accepted: 09/22/2023] [Indexed: 10/20/2023] Open
Abstract
Background There are limited data about the prevalence of cardiovascular (CV) risk factors and the findings of CV workup among kidney transplant (KTx) recipients (KTRs) in Saudi Arabia. Methods A single-center retrospective study of KTRs who underwent KTx from 2017 to 2020 was performed. We reviewed the prevalence of CV risk factors and the results of the pre-KTx CV workup which was derived from the American Heart Association guidelines. Results We included 254 KTRs. The mean age was 43.1 ± 15.9 years, and 55.5% were men and 79.5% were living-donor KTRs. Pre-emptive KTx was 9.8%, peritoneal dialysis was 11.8%, and hemodialysis was 78.3% (arteriovenous fistula: 33.1% versus hemodialysis catheter: 66.9%). The mean dialysis vintage was 4.8 ± 3.3 years for deceased-donor KTRs versus 2.4 ± 2.6 years for living-donor KTRs. CV risk factors were hypertension: 76%, diabetes: 40.6% (type 1 : 25.2% versus type 2 : 74.7%), hyperlipidemia (low-density lipoprotein >2.6 mmol/L): 40.2%, coronary artery disease (CAD): 12.6%, smoking: 9.1%, peripheral vascular disease: 2.8%, and cerebral vascular disease: 2.4%. The prevalence of obesity stage 1 was 19.7% and obesity stage 2 was 4%. Left ventricular hypertrophy was present in 38.5%. The ejection fraction was abnormal (<55%) in 22%. Abnormal wall motion was present in 34 patients (13.4%). A cardiac (PET-CT) stress test was conducted on 129 patients (50.8%) which showed abnormal perfusion in 37 patients (28.7%). Out of those who required PET-CT, 18.6% had a coronary artery calcium scoring (CACS) of more than 400, 41.8% had a CACS of zero, 29.4% had a CACS of 1-100, and 14.7% had a CACS of 100-400. Coronary angiogram was required in only 41 patients (16.1%), 12 (29.3%) required coronary interventions, 25 (61%) were treated medically, and 4 (9.8%) did not have any CAD. CT scans of pelvic arteries were performed in 118 patients (46.5%). It showed moderate or severe calcifications in only 7 patients (5.9%), whereas it was normal in 97 patients (82.2%), or it showed only mild calcifications in 14 patients (11.9%). Conclusion This study outlines the prevalence of CV risk factors and the findings of the pretransplant CV workup among KTx candidates who underwent KTx. Multicenter national studies will be helpful to validate the generalizability of these findings.
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Affiliation(s)
- Ziad Arabi
- Division of Nephrology, Department of Medicine, King Abdulaziz Medical City, Riyadh, Saudi Arabia
- King Abdullah International Medical Research Center, College of Medicine, Riyadh, Saudi Arabia
- King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Mohammed H. Tawhari
- Division of Nephrology, Department of Medicine, King Abdulaziz Medical City, Riyadh, Saudi Arabia
- King Abdullah International Medical Research Center, College of Medicine, Riyadh, Saudi Arabia
- King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Haneen S. Al Rajih
- Division of Nephrology, Department of Medicine, King Abdulaziz Medical City, Riyadh, Saudi Arabia
- King Abdullah International Medical Research Center, College of Medicine, Riyadh, Saudi Arabia
- King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Talha M. Youssouf
- Division of Nephrology, Department of Medicine, King Abdulaziz Medical City, Riyadh, Saudi Arabia
- King Abdullah International Medical Research Center, College of Medicine, Riyadh, Saudi Arabia
- King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Mohamad Y. Abdulgadir
- Division of Nephrology, Department of Medicine, King Abdulaziz Medical City, Riyadh, Saudi Arabia
- King Abdullah International Medical Research Center, College of Medicine, Riyadh, Saudi Arabia
- King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
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Gordon CE, Adam GP, Jadoul M, Martin P, Balk EM. Kidney Transplantation From Hepatitis C Virus-Infected Donors to Uninfected Recipients: A Systematic Review for the KDIGO 2022 Hepatitis C Clinical Practice Guideline Update. Am J Kidney Dis 2023; 82:410-418. [PMID: 37061019 DOI: 10.1053/j.ajkd.2022.12.019] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2022] [Accepted: 12/31/2022] [Indexed: 04/17/2023]
Abstract
RATIONALE & OBJECTIVE Direct-acting antiviral (DAA) treatment of hepatitis C virus (HCV) infection in patients with chronic kidney disease (CKD) has made transplantation of kidneys from HCV-infected donors to uninfected recipients (D+/R-) feasible. To facilitate an update to the 2018 KDIGO guideline for patients with CKD and HCV, we conducted a systematic review of HCV D+/R-kidney transplantation coupled with DAA treatment. STUDY DESIGN Systematic review and meta-analysis. SETTING & STUDY POPULATIONS We included studies of HCV D+/R-kidney transplantations that used any DAA protocol. SELECTION CRITERIA FOR STUDIES Based on a search of PubMed, Embase, Cochrane, CINAHL, and ClinicalTrials.gov through February 1, 2022, conferences from 2019 to 2021, and the 2018 KDIGO HCV guideline we identified single-group (D+/R-) or comparative studies of D+/R-versus D-/R-kidney transplantation. DATA EXTRACTION Conducted in SRDR-Plus with review by a second researcher. ANALYTICAL APPROACH Maximum likelihood meta-analyses; the certainty of evidence was assessed per GRADE (Grading of Recommendations Assessment, Development and Evaluation). RESULTS We identified 16 studies (N=557). A sustained viral response at 12 weeks after treatment (SVR12) was observed in 97.7% (95% CI, 96.3%-98.8%). Ultrashort duration treatment (≤8 days) resulted in viremia requiring standard-course DAA treatment in some patients, all of whom achieved SVR12 after 1 or rarely 2 DAA courses. Serious adverse events from DAA treatment were rare after D+/R-transplantation (0.4% [95% CI, 0.1%-2.8%]). At≥1 year after D+/R-transplantation, recipient death occurred in 2.1% (95% CI, 0.9-3.7) and allograft survival was 97.6% (95% CI, 95.7%-98.9%). Estimated glomerular filtration rate 1 year after transplantation ranged from 46 to 74mL/min/1.73m2. LIMITATIONS Analyses were generally based on low-certainty evidence. Uncertainty exists about the long-term safety and efficacy of D+/R-transplantation. Few studies investigated ultrashort treatment courses. CONCLUSIONS Kidney transplantation from HCV-infected donors to uninfected recipients followed by DAA treatment appears to be safe and associated with excellent 1-year clinical outcomes. PLAIN-LANGUAGE SUMMARY Due to the high efficacy of direct-acting antivirals (DAA), the use of kidneys from HCV-infected deceased donors may increase rates of kidney transplantation. We conducted a systematic review for the 2022 KDIGO Clinical Practice Guideline on Hepatitis C to evaluate the safety and efficacy of kidney transplantation from HCV-infected donors to uninfected recipients (D+/R-) followed by DAA therapy. Sixteen studies comprising 557 patients revealed high rates of sustained viral response, low rates of adverse events, and excellent patient and allograft survival 1 year after transplantation. Kidney transplantation from HCV-infected deceased donors to uninfected recipients treated with DAA appears safe and effective. Future studies should investigate shorter treatment durations, monitor safety, and obtain longer-term efficacy data.
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Affiliation(s)
- Craig E Gordon
- Division of Nephrology, Department of Medicine, School of Medicine, Tufts University, Boston, Massachusetts.
| | - Gaelen P Adam
- Brown Center for Evidence Synthesis in Health, Brown School of Public Health, Brown University, Providence, Rhode Island
| | - Michel Jadoul
- Department of Nephrology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium
| | - Paul Martin
- Division of Digestive Health and Liver Diseases, School of Medicine, University of Miami, Miami, Florida
| | - Ethan M Balk
- Brown Center for Evidence Synthesis in Health, Brown School of Public Health, Brown University, Providence, Rhode Island
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de-Miguel-Yanes JM, Lopez-de-Andres A, Jimenez-Garcia R, Zamorano-Leon JJ, Carabantes-Alarcon D, Omaña-Palanco R, Hernández-Barrera V, del-Barrio JL, de-Miguel-Diez J, Cuadrado-Corrales N. Association between Hospital-Acquired Pneumonia and In-Hospital Mortality in Solid Organ Transplant Admissions: An Observational Analysis in Spain, 2004-2021. J Clin Med 2023; 12:5532. [PMID: 37685599 PMCID: PMC10488258 DOI: 10.3390/jcm12175532] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2023] [Revised: 08/15/2023] [Accepted: 08/23/2023] [Indexed: 09/10/2023] Open
Abstract
(1) Background: To analyze the association between hospital-acquired pneumonia (HAP) and in-hospital mortality (IHM) during hospital admission for solid organ transplant in Spain during 2004-2021. (2) Methods: We used national hospital discharge data to select all hospital admissions for kidney, liver, heart, and lung transplants. We stratified the data according to HAP status. To examine time trends, we grouped data into three consecutive 6-year periods (2004-2009; 2010-2015; and 2016-2021). We assessed in-hospital mortality (IHM) in logistic regression analyses and obtained odds ratios (ORs) with their 95% confidence intervals (CIs). (3) Results: We identified a total of 71,827 transplants (45,262, kidney; 18,127, liver; 4734, heart; and 4598, lung). Two thirds of the patients were men. Overall, the rate of HAP during admission was 2.6% and decreased from 3.0% during 2004-2009 to 2.4% during 2016-2021. The highest rate of HAP corresponded to lung transplant (9.4%), whereas we found the lowest rate for kidney transplant (1.1%). Rates of HAP for liver and heart transplants were 3.8% and 6.3%, respectively. IHM was significantly lower during 2016-2021 compared to 2004-2009 for all types of transplants (ORs (CIs) = 0.65 (0.53-0.79) for kidney; 0.73 (0.63-0.84) for liver; 0.72 (0.59-0.87) for heart; and 0.39 (0.31-0.47) for lung). HAP was associated with IHM for all types of transplants (ORs (CIs) = 4.47 (2.85-9.08) for kidney; 2.96 (2.34-3.75) for liver; 1.86 (1.34-2.57) for heart; and 2.97 (2.24-3.94) for lung). (4) Conclusions: Rates of HAP during admission for solid organ transplant differ depending on the type of transplant. Although IHM during admission for solid organ transplant has decreased over time in our country, HAP persists and is associated with a higher IHM after accounting for potential confounding variables.
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Affiliation(s)
- José M. de-Miguel-Yanes
- Internal Medicine Department, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Universidad Complutense de Madrid, 28040 Madrid, Spain;
| | - Ana Lopez-de-Andres
- Department of Public Health & Maternal and Child Health, Faculty of Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain; (R.J.-G.); (J.J.Z.-L.); (D.C.-A.); (R.O.-P.); (N.C.-C.)
| | - Rodrigo Jimenez-Garcia
- Department of Public Health & Maternal and Child Health, Faculty of Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain; (R.J.-G.); (J.J.Z.-L.); (D.C.-A.); (R.O.-P.); (N.C.-C.)
| | - José Javier Zamorano-Leon
- Department of Public Health & Maternal and Child Health, Faculty of Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain; (R.J.-G.); (J.J.Z.-L.); (D.C.-A.); (R.O.-P.); (N.C.-C.)
| | - David Carabantes-Alarcon
- Department of Public Health & Maternal and Child Health, Faculty of Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain; (R.J.-G.); (J.J.Z.-L.); (D.C.-A.); (R.O.-P.); (N.C.-C.)
| | - Ricardo Omaña-Palanco
- Department of Public Health & Maternal and Child Health, Faculty of Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain; (R.J.-G.); (J.J.Z.-L.); (D.C.-A.); (R.O.-P.); (N.C.-C.)
| | - Valentín Hernández-Barrera
- Preventive Medicine and Public Health Teaching and Research Unit, Health Sciences Faculty, Rey Juan Carlos University, 28933 Alcorcón, Spain; (V.H.-B.); (J.L.d.-B.)
| | - Jose Luis del-Barrio
- Preventive Medicine and Public Health Teaching and Research Unit, Health Sciences Faculty, Rey Juan Carlos University, 28933 Alcorcón, Spain; (V.H.-B.); (J.L.d.-B.)
| | - Javier de-Miguel-Diez
- Respiratory Care Department, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Universidad Complutense de Madrid, 28040 Madrid, Spain;
| | - Natividad Cuadrado-Corrales
- Department of Public Health & Maternal and Child Health, Faculty of Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain; (R.J.-G.); (J.J.Z.-L.); (D.C.-A.); (R.O.-P.); (N.C.-C.)
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Turolo S, Edefonti A, Syren ML, Montini G. Pharmacogenomics of Old and New Immunosuppressive Drugs for Precision Medicine in Kidney Transplantation. J Clin Med 2023; 12:4454. [PMID: 37445489 DOI: 10.3390/jcm12134454] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Revised: 06/16/2023] [Accepted: 06/28/2023] [Indexed: 07/15/2023] Open
Abstract
Kidney transplantation is the preferred therapeutic option for end-stage kidney disease, but, despite major therapeutic advancements, allograft rejection continues to endanger graft survival. Every patient is unique due to his or her clinical history, drug metabolism, genetic background, and epigenetics. For this reason, examples of "personalized medicine" and "precision medicine" have steadily increased in recent decades. The final target of precision medicine is to maximize drug efficacy and minimize toxicity for each individual patient. Immunosuppressive drugs, in the setting of kidney transplantation, require a precise dosage to avoid either adverse events (overdosage) or a lack of efficacy (underdosage). In this review, we will explore the knowledge regarding the pharmacogenomics of the main immunosuppressive medications currently utilized in kidney transplantation. We will focus on clinically relevant pharmacogenomic data, that is, the polymorphisms of the genes that metabolize immunosuppressive drugs.
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Affiliation(s)
- Stefano Turolo
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Pediatric Nephrology, Dialysis and Transplant Unit, 20122 Milan, Italy
| | - Alberto Edefonti
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Pediatric Nephrology, Dialysis and Transplant Unit, 20122 Milan, Italy
| | - Marie Luise Syren
- Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy
| | - Giovanni Montini
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Pediatric Nephrology, Dialysis and Transplant Unit, 20122 Milan, Italy
- Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy
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