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1
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Tsiakas S, Angelousi A, Benetou V, Orfanos P, Xagas E, Boletis J, Marinaki S. Hypothalamic-Pituitary-Adrenal Axis Activity and Metabolic Disorders in Kidney Transplant Recipients on Long-Term Glucocorticoid Therapy. J Clin Med 2024; 13:6712. [PMID: 39597857 PMCID: PMC11594445 DOI: 10.3390/jcm13226712] [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: 09/25/2024] [Revised: 11/01/2024] [Accepted: 11/06/2024] [Indexed: 11/29/2024] Open
Abstract
Background/Objectives: Glucocorticoids are commonly used for maintenance immunosuppressive therapy in kidney transplant recipients (KTRs). We aimed to investigate the prevalence of hypothalamic-pituitary-adrenal (HPA) axis suppression and its association with metabolic disorders in stable KTRs on low-dose glucocorticoids. Methods: This cross-sectional study included adult KTRs on low-dose glucocorticoids. HPA axis suppression was defined as baseline morning cortisol < 5 μg/dL. Adrenocorticotropic hormone (ACTH), dehydroepiandrosterone-sulphate (DHEAS) and 24 h urinary free cortisol (UFC) levels were also assessed. Examined metabolic disorders included hypertension, dyslipidemia, central obesity and post-transplant diabetes mellitus (PTDM). Results: Eighty adult KTRs with a median 57 months (IQR 24-102) since transplantation were included in the study. The mean prednisolone dose was 5.0 ± 1.3 mg/day. Baseline cortisol < 5.0 μg/dL was observed in 27.5% of the KTRs. Participants with baseline cortisol < 5.0 μg/dL were older (55.1 vs. 47.4 years, p = 0.023) and had had a transplant for a longer time (101.4 vs. 67.0 months, p = 0.043), compared with the rest of the cohort. Baseline cortisol correlated positively with ACTH (rho = 0.544, p < 0.001), DHEAS (rho:0.459, p < 0.001) and UFC (rho: 0.377, p = 0.002). The area under the receiver-operating characteristic curve for ACTH as a predictor of baseline cortisol > 5.0 μg/dL was 0.79 [95% confidence interval (CI): 0.68-0.89]. After adjustment for covariates, HPA axis suppression was not associated with the examined metabolic disorders. Conclusions: Our study showed that stable KTRs on chronic low-dose glucocorticoids exhibited an increased prevalence of HPA axis suppression. ACTH may serve as a surrogate biomarker for HPA axis activity in this population. Further research could evaluate the association of glucocorticoid-induced HPA axis inhibition with metabolic disorders.
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Affiliation(s)
- Stathis Tsiakas
- Department of Nephrology and Renal Transplantation, Medical School, National and Kapodistrian University of Athens, Laiko Hospital, 11527 Athens, Greece; (S.T.); (E.X.); (J.B.); (S.M.)
| | - Anna Angelousi
- Unit of Endocrinology, First Department of Internal Medicine, Laikon Hospital, Center of Excellence of Endocrine Tumours, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Vassiliki Benetou
- Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece; (V.B.); (P.O.)
| | - Philippos Orfanos
- Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece; (V.B.); (P.O.)
| | - Efstathios Xagas
- Department of Nephrology and Renal Transplantation, Medical School, National and Kapodistrian University of Athens, Laiko Hospital, 11527 Athens, Greece; (S.T.); (E.X.); (J.B.); (S.M.)
| | - John Boletis
- Department of Nephrology and Renal Transplantation, Medical School, National and Kapodistrian University of Athens, Laiko Hospital, 11527 Athens, Greece; (S.T.); (E.X.); (J.B.); (S.M.)
| | - Smaragdi Marinaki
- Department of Nephrology and Renal Transplantation, Medical School, National and Kapodistrian University of Athens, Laiko Hospital, 11527 Athens, Greece; (S.T.); (E.X.); (J.B.); (S.M.)
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Acharya S, Lama S, Kanigicherla DA. Anti-thymocyte globulin for treatment of T-cell-mediated allograft rejection. World J Transplant 2023; 13:299-308. [PMID: 38174145 PMCID: PMC10758678 DOI: 10.5500/wjt.v13.i6.299] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2023] [Revised: 11/01/2023] [Accepted: 11/17/2023] [Indexed: 12/15/2023] Open
Abstract
Anti-thymocyte globulin (ATG) is a pivotal immunosuppressive therapy utilized in the management of T-cell-mediated rejection and steroid-resistant rejection among renal transplant recipients. Commercially available as Thymoglobulin (rabbit-derived, Sanofi, United States), ATG-Fresenius S (rabbit-derived), and ATGAM (equine-derived, Pfizer, United States), these formulations share a common mechanism of action centered on their interaction with cell surface markers of immune cells, imparting immunosuppressive effects. Although the prevailing mechanism predominantly involves T-cell depletion via the com plement-mediated pathway, alternate mechanisms have been elucidated. Optimal dosing and treatment duration of ATG have exhibited variance across ran domised trials and clinical reports, rendering the establishment of standardized guidelines a challenge. The spectrum of risks associated with ATG administration spans from transient adverse effects such as fever, chills, and skin rash in the acute phase to long-term concerns related to immunosuppression, including susceptibility to infections and malignancies. This comprehensive review aims to provide a thorough exploration of the current understanding of ATG, encom passing its mechanism of action, clinical utility in the treatment of acute renal graft rejections, specifically steroid-resistant cases, efficacy in rejection episode reversal, and a synthesis of findings from different eras of maintenance immunosuppression. Additionally, it delves into the adverse effects associated with ATG therapy and its impact on long-term graft function. Furthermore, the review underscores the existing gaps in evidence, particularly in the context of the Banff classification of rejections, and highlights the challenges faced by clinicians when navigating the available literature to strike the optimal balance between the risks and benefits of ATG utilization in renal transplantation.
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Affiliation(s)
- Sumit Acharya
- Department of Nephrology, Shahid Dharmabhakta National Transplant Center, Bhaktapur 44800, Nepal
| | - Suraj Lama
- Department of Nephrology, Shahid Dharmabhakta National Transplant Center, Bhaktapur 44800, Nepal
| | - Durga Anil Kanigicherla
- Department of Renal Medicine, Manchester University NHS Foundation Trust, Manchester M13 9WL, United Kingdom
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Sagnes J, Battistella P, Paunet T, Mariano-Goulart D, Kucharczak F. Evaluation of 18-FDG PET diagnostic capabilities for cancer screening in heart transplant patients, a retrospective study. Medicine (Baltimore) 2023; 102:e35296. [PMID: 37773869 PMCID: PMC10545140 DOI: 10.1097/md.0000000000035296] [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: 07/10/2023] [Accepted: 08/29/2023] [Indexed: 10/01/2023] Open
Abstract
Evaluate 18-FDG positron emission tomography (PET) diagnostic capabilities for cancer screening in heart transplant patients. We conducted an anonymized retrospective observational study of heart transplant patients followed in the University Hospital of Montpellier, France. We analyzed 303 18-FDG PET from 158 patients. We compared demographic and clinical characteristics through uni- and multivariate analysis: in the cancer-free group, comparisons were made between the PET false positive (FP) group versus true negative (TN), and in the cancer group, comparisons were made between the PET false negative (FN) group versus true positive (TP). Out of the 303 exams, we found 245 TN, 26 TP, 26 FP and 6 FN. The sensitivity rate was calculated at 81%, the specificity rate at 90%, the positive predictive value at 50%, and the negative predictive value at 97%. The multivariate analysis showed an association between FP diagnosis and graft-PET delay (P value = .046, OR = 5.14, 95% CI [1.18-32.4]) and creatine reactive protein (CRP) ≥ 10 mg/L (P value = .042, OR = 4.21, 95% CI [1.02-17.2]). The estimated probability of FP by logit regression was 0.48 with 95% CI [0.21-0.77] when graft-PET delay ≥ 6 years and CRP ≥ 10 mg/L. No significative statistical link was found for the demographic or clinical characteristics in the FN group of patients with cancer, except for sex (all FN were men). 18-FDG PET performed very well in the follow-up of heart transplant patients for neoplasia screening, with better specificity than sensitivity. However, the study showed that almost 50% of FP can be predicted by considering only the graft-PET delay and CRP.
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Affiliation(s)
- Julie Sagnes
- Nuclear Medicine Department, Lapeyronie Hospital, Montpellier University Hospitals, Montpellier, France
| | - Pascal Battistella
- Cardiology Department, Arnaud-de-Villeneuve Hospital, Montpellier University Hospitals, PhyMedExp, INSERM, CNRS, Montpellier University, Montpellier, France
| | - Tom Paunet
- Nuclear Medicine Department, Lapeyronie Hospital, Montpellier University Hospitals, Montpellier, France
| | - Denis Mariano-Goulart
- Nuclear Medicine Department, Lapeyronie Hospital, Montpellier University Hospitals, Montpellier, France
- Cardiology Department, Arnaud-de-Villeneuve Hospital, Montpellier University Hospitals, PhyMedExp, INSERM, CNRS, Montpellier University, Montpellier, France
| | - Florentin Kucharczak
- Nuclear Medicine Department, Lapeyronie Hospital, Montpellier University Hospitals, Montpellier, France
- Department of Biostatistics, Epidemiology, Public Health and Methodological Innovation, Nîmes University Hospital, Nîmes, France
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Pediatric Onco-Nephrology: Time to Spread the Word-Part II: Long-Term Kidney Outcomes in Survivors of Childhood Malignancy and Malignancy after Kidney Transplant. Pediatr Nephrol 2022; 37:1285-1300. [PMID: 34490519 DOI: 10.1007/s00467-021-05172-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2020] [Revised: 05/24/2021] [Accepted: 06/07/2021] [Indexed: 12/24/2022]
Abstract
Onco-nephrology is a recent and evolving medical subspecialty devoted to the care of patients with kidney disease and unique kidney-related complications in the context of cancer and its treatments, recognizing that management of kidney disease as well as the cancer itself will improve survival and quality of life. While this area has received much attention in the adult medicine sphere, similar emphasis in the pediatric realm has not yet been realized. As in adults, kidney involvement in children with cancer extends beyond the time of initial diagnosis and treatment. Many interventions, such as chemotherapy, stem cell transplant, radiation, and nephrectomy, have long-term kidney effects, including the development of chronic kidney disease (CKD) with subsequent need for dialysis and/or kidney transplant. Thus, with the improved survival of children with malignancy comes the need for ongoing monitoring of kidney function and early mitigation of kidney-related comorbidities. In addition, children with kidney transplant are at higher risk of developing malignancies than their age-matched peers. Pediatric nephrologists thus need to be aware of issues related to cancer and its treatments as they impact their own patients. These facts emphasize the necessity of pediatric nephrologists and oncologists working closely together in managing these children and highlight the importance of bringing the onco-nephrology field to our growing list of pediatric nephrology subspecialties.
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Ashkar MH, Chen J, Shy C, Crippin JS, Chen CH, Sayuk GS, Davidson NO. Increased Risk of Advanced Colonic Adenomas and Timing of Surveillance Colonoscopy Following Solid Organ Transplantation. Dig Dis Sci 2022; 67:1858-1868. [PMID: 33973084 DOI: 10.1007/s10620-021-06987-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2020] [Accepted: 03/30/2021] [Indexed: 12/18/2022]
Abstract
BACKGROUND Detection and removal of colonic adenomatous polyps (CAP) decreases colorectal cancer (CRC) development, particularly with more or larger polyps or polyps with advanced villous/dysplastic histology. Immunosuppression following solid organ transplantation (SOT) may accelerate CAP development and progression compared to average-risk population but the benefit of earlier colonoscopic surveillance is unclear. AIMS Study the impact of maintenance immunosuppression post-SOT on developmental timing, multiplicity and pathological features of CAP, by measuring incidence of advanced CAP (villous histology, size ≥ 10 mm, ≥ 3 polyps, presence of dysplasia) post-SOT and the incidence of newly diagnosed CRC compared to average-risk age-matched population. METHODS Single-center retrospective cohort study of SOT recipients. RESULTS 295 SOT recipients were included and were compared with 291 age-matched average-risk controls. The mean interval between screening and surveillance colonoscopies between SOT and control groups was 6.3 years vs 5.9 years (p = 0.13). Post-SOT maintenance immunosuppression mean duration averaged 59.9 months at surveillance colonoscopy. On surveillance examinations, SOT recipients exhibited more advanced (≥ 10 mm) adenomas compared to matched controls (9.2% vs. 3.8%, p = 0.034; adjusted OR 2.38; 95% CI 1.07-5.30). CONCLUSION SOT recipients appear at higher risk for developing advanced CAP, suggesting that earlier surveillance should be considered.
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Affiliation(s)
- Motaz H Ashkar
- Department of Medicine, Division of Gastroenterology, School of Medicine and Barnes-Jewish Hospital, Washington University in St. Louis, 660 S Euclid Ave, St Louis, MO, 63110, USA
| | - Jacqueline Chen
- Department of Medicine, Division of Gastroenterology, School of Medicine and Barnes-Jewish Hospital, Washington University in St. Louis, 660 S Euclid Ave, St Louis, MO, 63110, USA
| | - Corey Shy
- Department of Medicine, School of Medicine and Barnes-Jewish Hospital, Washington University in St. Louis, St. Louis, MO, 63110, USA
| | - Jeffrey S Crippin
- Department of Medicine, Division of Gastroenterology, School of Medicine and Barnes-Jewish Hospital, Washington University in St. Louis, 660 S Euclid Ave, St Louis, MO, 63110, USA
| | - Chien-Huan Chen
- Department of Medicine, Division of Gastroenterology, School of Medicine and Barnes-Jewish Hospital, Washington University in St. Louis, 660 S Euclid Ave, St Louis, MO, 63110, USA
| | - Gregory S Sayuk
- Department of Medicine, Division of Gastroenterology, School of Medicine and Barnes-Jewish Hospital, Washington University in St. Louis, 660 S Euclid Ave, St Louis, MO, 63110, USA
| | - Nicholas O Davidson
- Department of Medicine, Division of Gastroenterology, School of Medicine and Barnes-Jewish Hospital, Washington University in St. Louis, 660 S Euclid Ave, St Louis, MO, 63110, USA.
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Dharia A, Boulet J, Sridhar VS, Kitchlu A. Cancer Screening in Solid Organ Transplant Recipients: A Focus on Screening Liver, Lung, and Kidney Recipients for Cancers Related to the Transplanted Organ. Transplantation 2022; 106:e64-e65. [PMID: 33795594 DOI: 10.1097/tp.0000000000003773] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Over the last few decades, the life expectancy of solid organ transplant recipients (SOTRs) has improved significantly. With SOTRs living longer, more recipients are dying from cancer. There is a reported 2- to 3-fold increased risk of cancer-specific mortality in SOTRs compared with the general population. Cancer in an SOTR can be de novo, recurrent, or donor-derived. Cancer screening in this population is crucial, as early detection and treatment may improve outcomes. In the absence of randomized controlled trials dedicated to SOTRs, clinicians rely on clinical practice guidelines from regional and national transplant societies; however, these may vary considerably across jurisdictions and transplanted organ. At present, no widely accepted consensus exists for cancer screening protocols in SOTRs, particularly with regard to screening for malignancy related to transplanted organ. Some SOTRs may be at higher risk of malignancies within the allograft. This is particularly the case in lung and liver recipients, though less common in kidney recipients who are at increased risk of developing renal cell cancer in their native kidneys. This increased risk has not been uniformly incorporated into screening recommendations for SOTRs. In this review, we summarize the cancer screening recommendations for SOTRs from various transplant organizations based on transplanted organ. This review also discusses the complexity and controversies surrounding screening of cancer in the allograft and future avenues to improve cancer detection in this context. More studies specific to SOTRs are required to form generalizable and evidence-based cancer screening guidelines, particularly with respect to cancer screening in the allograft.
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Affiliation(s)
- Atit Dharia
- Division of Nephrology, Department of Medicine, University Health Network, Toronto General Hospital, Toronto, ON, Canada
| | - Jacinthe Boulet
- Division of Cardiology, Department of Medicine, Montreal Heart Institute, Montreal, QC, Canada
| | - Vikas S Sridhar
- Division of Nephrology, Department of Medicine, University Health Network, Toronto General Hospital, Toronto, ON, Canada
| | - Abhijat Kitchlu
- Division of Nephrology, Department of Medicine, University Health Network, Toronto General Hospital, Toronto, ON, Canada
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7
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Ben-David E, Hull R, Banerjee D. Diabetes mellitus in dialysis and renal transplantation. Ther Adv Endocrinol Metab 2021; 12:20420188211048663. [PMID: 34631007 PMCID: PMC8495524 DOI: 10.1177/20420188211048663] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Accepted: 08/29/2021] [Indexed: 12/31/2022] Open
Abstract
Diabetes mellitus is the commonest cause of end-stage kidney failure worldwide and is a proven and significant risk factor for the development of cardiovascular disease. Renal impairment has a significant impact on the physiology of glucose homeostasis as it reduces tissue sensitivity to insulin and reduces insulin clearance. Renal replacement therapy itself affects glucose control: peritoneal dialysis may induce hyperglycaemia due to glucose-rich dialysate and haemodialysis often causes hypoglycaemia due to the relatively low concentration of glucose in the dialysate. Autonomic neuropathy which is common in chronic kidney disease (CKD) and diabetes increases the risk for asymptomatic hypoglycaemia. Pharmacological options for improving glycaemic control are limited due to alterations to drug metabolism. Impaired glucose tolerance and diabetes are also common in the post-kidney-transplant setting and increase the risk of graft failure and mortality. This review seeks to summarise the literature and tackle the intricacies of glycaemic management in patients with CKD who are either on maintenance haemodialysis or have received a kidney transplant. It outlines changes to glycaemic targets, monitoring of glycaemic control, the use of oral hypoglycaemic agents, the management of severe hyperglycaemia in dialysis and kidney transplantation patients.
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Affiliation(s)
- Eyal Ben-David
- Renal and Transplantation Unit, St George's University Hospitals NHS Foundation Trust, London, UK
| | - Richard Hull
- Renal and Transplantation Unit, St George's University Hospitals NHS Foundation Trust, London, UK
| | - Debasish Banerjee
- Renal and Transplantation Unit, St George's University Hospitals NHS Foundation Trust, Room G2.113, Second Floor, Grosvenor Wing, Blackshaw Road, Tooting, London SW17 0QT, UK
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Buxeda A, Redondo-Pachón D, Pérez-Sáez MJ, Crespo M, Pascual J. Sex differences in cancer risk and outcomes after kidney transplantation. Transplant Rev (Orlando) 2021; 35:100625. [PMID: 34020178 DOI: 10.1016/j.trre.2021.100625] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Revised: 04/27/2021] [Accepted: 04/28/2021] [Indexed: 02/06/2023]
Abstract
Kidney transplant recipients (KTRs) experience a two- to four-fold increased risk of developing and dying from cancer compared with the general population. High cancer risk results from the interaction of both modifiable and non-modifiable factors. This mapping review explores the impact of sex disparity on cancer's increased incidence and mortality after kidney transplantation (KT). In terms of age, population-based studies indicate that younger recipients of both sexes experience a higher risk of cancer, but this is more pronounced in young women. On the contrary, older men are more likely to be diagnosed with cancer, although their increased risk is not statistically significant compared with the general population. Regarding cancer type, studies show an increased risk of Kaposi sarcoma, gynecologic and lung cancer in women, and bladder and kidney cancer in men. Immune-related cancers such as pos-transplant lymphoproliferative disorders and melanoma are increased in both sexes. Mortality also shows differences between sexes. Although cancer is the second cause of death in both male and female KTRs, studies show higher overall mortality in men and elderly recipients. However, the relative risk of cancer mortality compared with the general population is higher at a younger age, with disparate results regarding sex. Female KTRs appear to die at a younger age than males when compared with the general population. Differences in cancer rates by sex after renal transplantation need further studies. A better understanding of sex-specific differences in cancer epidemiology after KT could help nephrologists to better address pre-transplant counseling, to establish early surveillance programs, and to plan modifiable risk factors such as immunosuppression.
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Affiliation(s)
- Anna Buxeda
- Department of Nephrology, Hospital del Mar, Barcelona, Spain.
| | | | | | - Marta Crespo
- Department of Nephrology, Hospital del Mar, Barcelona, Spain
| | - Julio Pascual
- Department of Nephrology, Hospital del Mar, Barcelona, Spain
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Ali H, Mohamed MM, Sharma A, Fulop T, Halawa A. Outcomes of Interleukin-2 Receptor Antagonist Induction Therapy in Standard-Risk Renal Transplant Recipients Maintained on Tacrolimus: A Systematic Review and Meta-Analysis. Am J Nephrol 2021; 52:279-291. [PMID: 33887727 DOI: 10.1159/000514454] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Accepted: 01/14/2021] [Indexed: 12/14/2022]
Abstract
INTRODUCTION The additive benefit of interleukin-2 receptor antagonist (IL2-RA) induction in standard-risk kidney transplant recipients, while maintained on tacrolimus-based immunosuppressive therapy, is uncertain. METHODS We divided the studies included in this meta-analysis into 2 groups: group A (included studies that used same dose of tacrolimus in both arms of each study) and group B (included studies that compared patients who received induction therapy and low-dose tacrolimus vs. those who received no-induction therapy and high dose of tacrolimus). RESULTS In group A, 11 studies were included (n = 2,886). IL2-RA induction therapy was not associated with significant differences in comparison to no-induction therapy in terms of acute rejection rates at 6 months post-transplant (risk ratio = 1.12 and 95% confidence interval [CI] range: 0.94-1.35) or graft survival at 1 year post-transplant (risk ratio = 0.78 and 95% CI range: 0.45-1.36). In group B, 2 studies were included (n = 669). There was no difference between both arms in terms of acute rejection rates (risk ratio = 0.62, with 95% CI range: 0.33-1.14) or graft survival (risk ratio = 1 and 95% CI range: 0.57-1.74). CONCLUSION IL2-RA induction therapy does not improve outcomes in patients maintained on tacrolimus-based immunotherapy in standard-risk population.
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Affiliation(s)
- Hatem Ali
- Renal Department, University Hospitals of Coventry and Warwickshire, Coventry, United Kingdom
| | - Mahmoud M Mohamed
- Division of Nephrology, Department of Medicine, University of Tennessee, Knoxville, Tennessee, USA
| | - Ajay Sharma
- Institute of Medical Sciences, Faculty of Medicine, University of Liverpool, Liverpool, United Kingdom
| | - Tibor Fulop
- Division of Nephrology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA
- Medicine Service, Ralph H. Johnson VA Medical Center, Charleston, South Carolina, USA
| | - Ahmed Halawa
- Institute of Medical Sciences, Faculty of Medicine, University of Liverpool, Liverpool, United Kingdom
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Tantisattamo E, Molnar MZ, Ho BT, Reddy UG, Dafoe DC, Ichii H, Ferrey AJ, Hanna RM, Kalantar-Zadeh K, Amin A. Approach and Management of Hypertension After Kidney Transplantation. Front Med (Lausanne) 2020; 7:229. [PMID: 32613001 PMCID: PMC7310511 DOI: 10.3389/fmed.2020.00229] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2019] [Accepted: 05/04/2020] [Indexed: 12/14/2022] Open
Abstract
Hypertension is one of the most common cardiovascular co-morbidities after successful kidney transplantation. It commonly occurs in patients with other metabolic diseases, such as diabetes mellitus, hyperlipidemia, and obesity. The pathogenesis of post-transplant hypertension is complex and is a result of the interplay between immunological and non-immunological factors. Post-transplant hypertension can be divided into immediate, early, and late post-transplant periods. This classification can help clinicians determine the etiology and provide the appropriate management for these complex patients. Volume overload from intravenous fluid administration is common during the immediate post-transplant period and commonly contributes to hypertension seen early after transplantation. Immunosuppressive medications and donor kidneys are associated with post-transplant hypertension occurring at any time point after transplantation. Transplant renal artery stenosis (TRAS) and obstructive sleep apnea (OSA) are recognized but common and treatable causes of resistant hypertension post-transplantation. During late post-transplant period, chronic renal allograft dysfunction becomes an additional cause of hypertension. As these patients develop more substantial chronic kidney disease affecting their allografts, fibroblast growth factor 23 (FGF23) increases and is associated with increased cardiovascular and all-cause mortality in kidney transplant recipients. The exact relationship between increased FGF23 and post-transplant hypertension remains poorly understood. Blood pressure (BP) targets and management involve both non-pharmacologic and pharmacologic treatment and should be individualized. Until strong evidence in the kidney transplant population exists, a BP of <130/80 mmHg is a reasonable target. Similar to complete renal denervation in non-transplant patients, bilateral native nephrectomy is another treatment option for resistant post-transplant hypertension. Native renal denervation offers promising outcomes for controlling resistant hypertension with no significant procedure-related complications. This review addresses the epidemiology, pathogenesis, and specific etiologies of post-transplant hypertension including TRAS, calcineurin inhibitor effects, OSA, and failed native kidney. The cardiovascular and survival outcomes related to post-transplant hypertension and the utility of 24-h blood pressure monitoring will be briefly discussed. Antihypertensive medications and their mechanism of actions relevant to kidney transplantation will be highlighted. A summary of guidelines from different professional societies for BP targets and antihypertensive medications as well as non-pharmacological interventions, including bilateral native nephrectomy and native renal denervation, will be reviewed.
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Affiliation(s)
- Ekamol Tantisattamo
- Division of Nephrology, Hypertension and Kidney Transplantation, Department of Medicine, Harold Simmons Center for Kidney Disease Research and Epidemiology, University of California Irvine School of Medicine, Orange, CA, United States.,Nephrology Section, Department of Medicine, Tibor Rubin Veterans Affairs Medical Center, VA Long Beach Healthcare System, Long Beach, CA, United States.,Section of Nephrology, Department of Internal Medicine, Multi-Organ Transplant Center, William Beaumont Hospital, Oakland University William Beaumont School of Medicine, Royal Oak, MI, United States
| | - Miklos Z Molnar
- Division of Nephrology, University of Tennessee Health Science Center, Memphis, TN, United States.,Methodist University Hospital Transplant Institute, Memphis, TN, United States.,Division of Transplant Surgery, Department of Surgery, University of Tennessee Health Science Center, Memphis, TN, United States
| | - Bing T Ho
- Division of Nephrology and Hypertension, Department of Medicine, Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
| | - Uttam G Reddy
- Division of Nephrology, Hypertension and Kidney Transplantation, Department of Medicine, Harold Simmons Center for Kidney Disease Research and Epidemiology, University of California Irvine School of Medicine, Orange, CA, United States.,Nephrology Section, Department of Medicine, Tibor Rubin Veterans Affairs Medical Center, VA Long Beach Healthcare System, Long Beach, CA, United States
| | - Donald C Dafoe
- Division of Transplantation, Department of Surgery, University of California Irvine School of Medicine, Orange, CA, United States
| | - Hirohito Ichii
- Division of Transplantation, Department of Surgery, University of California Irvine School of Medicine, Orange, CA, United States
| | - Antoney J Ferrey
- Division of Nephrology, Hypertension and Kidney Transplantation, Department of Medicine, Harold Simmons Center for Kidney Disease Research and Epidemiology, University of California Irvine School of Medicine, Orange, CA, United States.,Nephrology Section, Department of Medicine, Tibor Rubin Veterans Affairs Medical Center, VA Long Beach Healthcare System, Long Beach, CA, United States
| | - Ramy M Hanna
- Division of Nephrology, Hypertension and Kidney Transplantation, Department of Medicine, Harold Simmons Center for Kidney Disease Research and Epidemiology, University of California Irvine School of Medicine, Orange, CA, United States
| | - Kamyar Kalantar-Zadeh
- Division of Nephrology, Hypertension and Kidney Transplantation, Department of Medicine, Harold Simmons Center for Kidney Disease Research and Epidemiology, University of California Irvine School of Medicine, Orange, CA, United States.,Nephrology Section, Department of Medicine, Tibor Rubin Veterans Affairs Medical Center, VA Long Beach Healthcare System, Long Beach, CA, United States
| | - Alpesh Amin
- Department of Medicine, University of California Irvine School of Medicine, Orange, CA, United States
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Ali H, Soliman KM, Shaheen I, Kim JJ, Kossi ME, Sharma A, Pararajasingam R, Halawa A. Rabbit anti-thymocyte globulin (rATG) versus IL-2 receptor antagonist induction therapies in tacrolimus-based immunosuppression era: a meta-analysis. Int Urol Nephrol 2020; 52:791-802. [PMID: 32170593 DOI: 10.1007/s11255-020-02418-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2019] [Accepted: 02/17/2020] [Indexed: 01/25/2023]
Abstract
BACKGROUND The aim of this meta-analysis is to explore the effect of IL-2RA vs rATG on the rate of acute rejection, post-transplant infections, and graft as well as patient's survival in standard- and high-risk renal transplant patients receiving tacrolimus-based maintenance immunotherapy. METHODS Random effects model was the method used for identifying risk difference. Confidence interval including the value 1 was used as evidence for statistically significant risk difference. Heterogeneity was assessed using Der Simonian analysis. Heterogeneity was evident at the level of P value < 0.1 RESULTS: The random effects model showed no significant differences in both acute rejection rates between IL-2RA and rATG induction therapies with relative risk of 1.24 graft survival with relative risk 0.90. Patient survival also did not demonstrate any significant difference with a relative risk of 1.19. Random effects for CMV infection showed a lesser tendency for CMV infection in IL-2RA group compared to ATG group the with a relative risk of 0.73.In subgroup analysis, the random effects model for acute rejection rates in high-risk transplants showed a higher risk of acute rejection in the IL-2RA group compared to rATG (relative risk equals 1.55) In standard-risk transplants, there were no significant differences between both groups with relative risk equals 1.02 CONCLUSIONS: This meta-analysis revealed no significant difference in patient and graft survival when using IL-2RA vs rATG with the tacrolimus-based maintenance immunosuppression era. However, subgroup analysis showed less incidence of rejection in high-risk renal transplant recipient's population using rATG compared to IL-2RA.
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Affiliation(s)
- Hatem Ali
- Department of Renal Medicine, Royal Stoke University Hospital, NHS Foundation Trust, Stoke-on-Trent, UK.,Faculty of Medicine, Institute of Medical Sciences, University of Liverpool, Liverpool, UK
| | - Karim M Soliman
- Division of Nephrology, Department of Medicine, Medical University of South Carolina, Charleston, SC, USA
| | - Ihab Shaheen
- Faculty of Medicine, Institute of Medical Sciences, University of Liverpool, Liverpool, UK.,Royal Hospital for Children, Glasgow, UK
| | - Jon Jin Kim
- Faculty of Medicine, Institute of Medical Sciences, University of Liverpool, Liverpool, UK.,Nottingham Children Hospital, Nottingham, UK
| | - Mohsen El Kossi
- Faculty of Medicine, Institute of Medical Sciences, University of Liverpool, Liverpool, UK.,Renal Department, Doncaster Royal Infirmary, Doncaster, UK
| | - Ajay Sharma
- Faculty of Medicine, Institute of Medical Sciences, University of Liverpool, Liverpool, UK.,Transplant Surgery Department, Royal Liverpool University Hospital, Liverpool, UK
| | - Ravi Pararajasingam
- Faculty of Medicine, Institute of Medical Sciences, University of Liverpool, Liverpool, UK.,Transplant Surgery Department, Sheffield Kidney Institute, Sheffield Teaching Hospitals, Sheffield, UK
| | - Ahmed Halawa
- Faculty of Medicine, Institute of Medical Sciences, University of Liverpool, Liverpool, UK. .,Transplant Surgery Department, Sheffield Kidney Institute, Sheffield Teaching Hospitals, Sheffield, UK.
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12
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Park CK, Fung K, Austin PC, Kim SJ, Singer LG, Baxter NN, Rochon PA, Chan AW. Incidence and Risk Factors of Keratinocyte Carcinoma After First Solid Organ Transplant in Ontario, Canada. JAMA Dermatol 2019; 155:1041-1048. [PMID: 31116351 DOI: 10.1001/jamadermatol.2019.0692] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Abstract
Importance Keratinocyte carcinoma (KC), also known as nonmelanoma skin cancer, is the most common malignancy after solid organ transplant. Epidemiologic data on posttransplant KC in North America are limited by a lack of KC capture in cancer and transplant registries. Objective To estimate the incidence and identify risk factors for posttransplant KC. Design, Setting, and Participants This population-based inception cohort study in Ontario, Canada, used linked administrative databases and a health insurance claims-based algorithm. Participants were adult recipients of a first kidney, liver, heart, or lung transplant from January 1, 1994, to December 31, 2012. The cohort (n = 10 198) was followed up to December 31, 2013. Data were analyzed from May 31, 2016, to April 21, 2017. Exposures Solid organ transplant with functioning graft. Main Outcomes and Measures Age- and sex-adjusted standardized incidence ratio for KC in the transplant cohort was compared with that in the general population. Cumulative incidence of posttransplant KC was estimated using cumulative incidence functions, accounting for the competing risks of death or kidney graft loss. The association between KC and patient-, transplant-, and health services-related factors was evaluated with a multivariable cause-specific hazards model. Results A total of 10 198 transplant recipients were included in the study. The median (interquartile range [IQR]) age at transplant was 51 (41-59) years, with most recipients being male (6608 [64.8%]) and white (5964 [58.5%]). Posttransplant KC was diagnosed in 1690 patients (16.6%) after a median (IQR) of 3.96 (1.94-7.09) years, with an incidence rate of 2.63 per 100 patient-years (95% CI, 2.51-2.76). The rate of KC was significantly higher after transplant compared with the general population (standardized incidence ratio, 6.61; 95% CI, 6.31-6.93). The highest 10-year cumulative incidence was in the subsets of patients with a history of pretransplant skin cancer (66.5%), older than 50 years at transplant (27.5% for 51-65 years; 40.5% for >65 years), and of the white race (24.1%). The strongest independent risk factors for KC included older age at transplant (adjusted hazard ratio [aHR], 9.27; 95% CI, 7.08-12.14 for >65 years vs 18-35 years), white vs black race (aHR, 8.50; 95% CI, 4.03-17.91), pretransplant invasive skin cancer (aHR, 4.30; 95% CI, 3.72-4.98), and posttransplant precancerous skin lesions (aHR, 4.32; 95% CI, 3.77-4.95). Conclusions and Relevance The incidence of KC appeared to be substantially increased after transplant, particularly in patients who were older at transplant, were white, and had a history of cancerous or precancerous skin tumors; intensified skin cancer screening, education, and early use of chemopreventive interventions may be warranted for these high-risk patient subsets.
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Affiliation(s)
- Christina K Park
- Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Kinwah Fung
- Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada
| | - Peter C Austin
- Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada
| | - S Joseph Kim
- Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada.,Department of Medicine, University of Toronto, Toronto, Ontario, Canada.,Division of Nephrology, University Health Network, Toronto, Ontario, Canada
| | - Lianne G Singer
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada.,Division of Respirology, University Health Network, Toronto, Ontario, Canada
| | - Nancy N Baxter
- Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada.,Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, Ontario, Canada.,Department of Surgery, St Michael's Hospital and University of Toronto, Toronto, Ontario, Canada
| | - Paula A Rochon
- Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada.,Department of Medicine, University of Toronto, Toronto, Ontario, Canada.,Women's College Research Institute, Women's College Hospital, Toronto, Ontario, Canada
| | - An-Wen Chan
- Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada.,Department of Medicine, University of Toronto, Toronto, Ontario, Canada.,Women's College Research Institute, Women's College Hospital, Toronto, Ontario, Canada.,Division of Dermatology, Women's College Hospital, Toronto, Ontario, Canada
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13
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Rifkin WJ, Manjunath A, Kimberly LL, Plana NM, Kantar RS, Bernstein GL, Diaz-Siso JR, Rodriguez ED. Long-distance care of face transplant recipients in the United States. J Plast Reconstr Aesthet Surg 2018; 71:1383-1391. [DOI: 10.1016/j.bjps.2018.05.019] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2017] [Revised: 04/10/2018] [Accepted: 05/27/2018] [Indexed: 11/15/2022]
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14
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Sprangers B, Nair V, Launay-Vacher V, Riella LV, Jhaveri KD. Risk factors associated with post-kidney transplant malignancies: an article from the Cancer-Kidney International Network. Clin Kidney J 2018; 11:315-329. [PMID: 29942495 PMCID: PMC6007332 DOI: 10.1093/ckj/sfx122] [Citation(s) in RCA: 96] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2017] [Accepted: 09/15/2017] [Indexed: 12/13/2022] Open
Abstract
In kidney transplant recipients, cancer is one of the leading causes of death with a functioning graft beyond the first year of kidney transplantation, and malignancies account for 8-10% of all deaths in the USA (2.6 deaths/1000 patient-years) and exceed 30% of deaths in Australia (5/1000 patient-years) in kidney transplant recipients. Patient-, transplant- and medication-related factors contribute to the increased cancer risk following kidney transplantation. While it is well established that the overall immunosuppressive dose is associated with an increased risk for cancer following transplantation, the contributive effect of different immunosuppressive agents is not well established. In this review we will discuss the different risk factors for malignancies after kidney transplantation.
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Affiliation(s)
- Ben Sprangers
- Department of Microbiology and Immunology, KU Leuven and Division of Nephrology, University Hospitals Leuven, Leuven, Belgium
- Department of Microbiology and Immunology, KU Leuven and Laboratory of Experimental Transplantation, University Hospitals Leuven, Leuven, Belgium
- Cancer-Kidney International Network, Brussels, Belgium
| | - Vinay Nair
- Department of Medicine, Division of Kidney Diseases and Hypertension, Hofstra Northwell School of Medicine, Hempstead, NY, USA
| | - Vincent Launay-Vacher
- Cancer-Kidney International Network, Brussels, Belgium
- Service ICAR and Department of Nephrology, Pitié-Salpêtrière University Hospital, Paris, France
| | - Leonardo V Riella
- Department of Medicine, Schuster Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Boston, MA, USA
| | - Kenar D Jhaveri
- Cancer-Kidney International Network, Brussels, Belgium
- Department of Medicine, Division of Kidney Diseases and Hypertension, Hofstra Northwell School of Medicine, Hempstead, NY, USA
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15
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Jones-Hughes T, Snowsill T, Haasova M, Coelho H, Crathorne L, Cooper C, Mujica-Mota R, Peters J, Varley-Campbell J, Huxley N, Moore J, Allwood M, Lowe J, Hyde C, Hoyle M, Bond M, Anderson R. Immunosuppressive therapy for kidney transplantation in adults: a systematic review and economic model. Health Technol Assess 2018; 20:1-594. [PMID: 27578428 DOI: 10.3310/hta20620] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND End-stage renal disease is a long-term irreversible decline in kidney function requiring renal replacement therapy: kidney transplantation, haemodialysis or peritoneal dialysis. The preferred option is kidney transplantation, followed by immunosuppressive therapy (induction and maintenance therapy) to reduce the risk of kidney rejection and prolong graft survival. OBJECTIVES To review and update the evidence for the clinical effectiveness and cost-effectiveness of basiliximab (BAS) (Simulect(®), Novartis Pharmaceuticals UK Ltd) and rabbit anti-human thymocyte immunoglobulin (rATG) (Thymoglobulin(®), Sanofi) as induction therapy, and immediate-release tacrolimus (TAC) (Adoport(®), Sandoz; Capexion(®), Mylan; Modigraf(®), Astellas Pharma; Perixis(®), Accord Healthcare; Prograf(®), Astellas Pharma; Tacni(®), Teva; Vivadex(®), Dexcel Pharma), prolonged-release tacrolimus (Advagraf(®) Astellas Pharma), belatacept (BEL) (Nulojix(®), Bristol-Myers Squibb), mycophenolate mofetil (MMF) (Arzip(®), Zentiva; CellCept(®), Roche Products; Myfenax(®), Teva), mycophenolate sodium (MPS) (Myfortic(®), Novartis Pharmaceuticals UK Ltd), sirolimus (SRL) (Rapamune(®), Pfizer) and everolimus (EVL) (Certican(®), Novartis) as maintenance therapy in adult renal transplantation. METHODS Clinical effectiveness searches were conducted until 18 November 2014 in MEDLINE (via Ovid), EMBASE (via Ovid), Cochrane Central Register of Controlled Trials (via Wiley Online Library) and Web of Science (via ISI), Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects and Health Technology Assessment (The Cochrane Library via Wiley Online Library) and Health Management Information Consortium (via Ovid). Cost-effectiveness searches were conducted until 18 November 2014 using a costs or economic literature search filter in MEDLINE (via Ovid), EMBASE (via Ovid), NHS Economic Evaluation Database (via Wiley Online Library), Web of Science (via ISI), Health Economic Evaluations Database (via Wiley Online Library) and the American Economic Association's electronic bibliography (via EconLit, EBSCOhost). Included studies were selected according to predefined methods and criteria. A random-effects model was used to analyse clinical effectiveness data (odds ratios for binary data and mean differences for continuous data). Network meta-analyses were undertaken within a Bayesian framework. A new discrete time-state transition economic model (semi-Markov) was developed, with acute rejection, graft function (GRF) and new-onset diabetes mellitus used to extrapolate graft survival. Recipients were assumed to be in one of three health states: functioning graft, graft loss or death. RESULTS Eighty-nine randomised controlled trials (RCTs), of variable quality, were included. For induction therapy, no treatment appeared more effective than another in reducing graft loss or mortality. Compared with placebo/no induction, rATG and BAS appeared more effective in reducing biopsy-proven acute rejection (BPAR) and BAS appeared more effective at improving GRF. For maintenance therapy, no treatment was better for all outcomes and no treatment appeared most effective at reducing graft loss. BEL + MMF appeared more effective than TAC + MMF and SRL + MMF at reducing mortality. MMF + CSA (ciclosporin), TAC + MMF, SRL + TAC, TAC + AZA (azathioprine) and EVL + CSA appeared more effective than CSA + AZA and EVL + MPS at reducing BPAR. SRL + AZA, TAC + AZA, TAC + MMF and BEL + MMF appeared to improve GRF compared with CSA + AZA and MMF + CSA. In the base-case deterministic and probabilistic analyses, BAS, MMF and TAC were predicted to be cost-effective at £20,000 and £30,000 per quality-adjusted life-year (QALY). When comparing all regimens, only BAS + TAC + MMF was cost-effective at £20,000 and £30,000 per QALY. LIMITATIONS For included trials, there was substantial methodological heterogeneity, few trials reported follow-up beyond 1 year, and there were insufficient data to perform subgroup analysis. Treatment discontinuation and switching were not modelled. FUTURE WORK High-quality, better-reported, longer-term RCTs are needed. Ideally, these would be sufficiently powered for subgroup analysis and include health-related quality of life as an outcome. CONCLUSION Only a regimen of BAS induction followed by maintenance with TAC and MMF is likely to be cost-effective at £20,000-30,000 per QALY. STUDY REGISTRATION This study is registered as PROSPERO CRD42014013189. FUNDING The National Institute for Health Research Health Technology Assessment programme.
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Affiliation(s)
- Tracey Jones-Hughes
- Peninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter, UK
| | - Tristan Snowsill
- Peninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter, UK
| | - Marcela Haasova
- Peninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter, UK
| | - Helen Coelho
- Peninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter, UK
| | - Louise Crathorne
- Peninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter, UK
| | - Chris Cooper
- Peninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter, UK
| | - Ruben Mujica-Mota
- Peninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter, UK
| | - Jaime Peters
- Peninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter, UK
| | - Jo Varley-Campbell
- Peninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter, UK
| | - Nicola Huxley
- Peninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter, UK
| | - Jason Moore
- Exeter Kidney Unit, Royal Devon and Exeter Foundation Trust Hospital, Exeter, UK
| | - Matt Allwood
- Peninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter, UK
| | - Jenny Lowe
- Peninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter, UK
| | - Chris Hyde
- Peninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter, UK
| | - Martin Hoyle
- Peninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter, UK
| | - Mary Bond
- Peninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter, UK
| | - Rob Anderson
- Peninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter, UK
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16
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Haasova M, Snowsill T, Jones-Hughes T, Crathorne L, Cooper C, Varley-Campbell J, Mujica-Mota R, Coelho H, Huxley N, Lowe J, Dudley J, Marks S, Hyde C, Bond M, Anderson R. Immunosuppressive therapy for kidney transplantation in children and adolescents: systematic review and economic evaluation. Health Technol Assess 2018; 20:1-324. [PMID: 27557331 DOI: 10.3310/hta20610] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND End-stage renal disease is a long-term irreversible decline in kidney function requiring kidney transplantation, haemodialysis or peritoneal dialysis. The preferred option is kidney transplantation followed by induction and maintenance immunosuppressive therapy to reduce the risk of kidney rejection and prolong graft survival. OBJECTIVES To systematically review and update the evidence for the clinical effectiveness and cost-effectiveness of basiliximab (BAS) (Simulect,(®) Novartis Pharmaceuticals) and rabbit antihuman thymocyte immunoglobulin (Thymoglobuline,(®) Sanofi) as induction therapy and immediate-release tacrolimus [Adoport(®) (Sandoz); Capexion(®) (Mylan); Modigraf(®) (Astellas Pharma); Perixis(®) (Accord Healthcare); Prograf(®) (Astellas Pharma); Tacni(®) (Teva); Vivadex(®) (Dexcel Pharma)], prolonged-release tacrolimus (Advagraf,(®) Astellas Pharma); belatacept (BEL) (Nulojix,(®) Bristol-Myers Squibb), mycophenolate mofetil (MMF) [Arzip(®) (Zentiva), CellCept(®) (Roche Products), Myfenax(®) (Teva), generic MMF is manufactured by Accord Healthcare, Actavis, Arrow Pharmaceuticals, Dr Reddy's Laboratories, Mylan, Sandoz and Wockhardt], mycophenolate sodium, sirolimus (Rapamune,(®) Pfizer) and everolimus (Certican,(®) Novartis Pharmaceuticals) as maintenance therapy in children and adolescents undergoing renal transplantation. DATA SOURCES Clinical effectiveness searches were conducted to 7 January 2015 in MEDLINE (via Ovid), EMBASE (via Ovid), Cochrane Central Register of Controlled Trials (via Wiley Online Library) and Web of Science [via Institute for Scientific Information (ISI)], Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects and Health Technology Assessment (HTA) (The Cochrane Library via Wiley Online Library) and Health Management Information Consortium (via Ovid). Cost-effectiveness searches were conducted to 15 January 2015 using a costs or economic literature search filter in MEDLINE (via Ovid), EMBASE (via Ovid), NHS Economic Evaluation Databases (via Wiley Online Library), Web of Science (via ISI), Health Economic Evaluations Database (via Wiley Online Library) and EconLit (via EBSCOhost). REVIEW METHODS Titles and abstracts were screened according to predefined inclusion criteria, as were full texts of identified studies. Included studies were extracted and quality appraised. Data were meta-analysed when appropriate. A new discrete time state transition economic model (semi-Markov) was developed; graft function, and incidences of acute rejection and new-onset diabetes mellitus were used to extrapolate graft survival. Recipients were assumed to be in one of three health states: functioning graft, graft loss or death. RESULTS Three randomised controlled trials (RCTs) and four non-RCTs were included. The RCTs only evaluated BAS and tacrolimus (TAC). No statistically significant differences in key outcomes were found between BAS and placebo/no induction. Statistically significantly higher graft function (p < 0.01) and less biopsy-proven acute rejection (odds ratio 0.29, 95% confidence interval 0.15 to 0.57) was found between TAC and ciclosporin (CSA). Only one cost-effectiveness study was identified, which informed NICE guidance TA99. BAS [with TAC and azathioprine (AZA)] was predicted to be cost-effective at £20,000-30,000 per quality-adjusted life year (QALY) versus no induction (BAS was dominant). BAS (with CSA and MMF) was not predicted to be cost-effective at £20,000-30,000 per QALY versus no induction (BAS was dominated). TAC (with AZA) was predicted to be cost-effective at £20,000-30,000 per QALY versus CSA (TAC was dominant). A model based on adult evidence suggests that at a cost-effectiveness threshold of £20,000-30,000 per QALY, BAS and TAC are cost-effective in all considered combinations; MMF was also cost-effective with CSA but not TAC. LIMITATIONS The RCT evidence is very limited; analyses comparing all interventions need to rely on adult evidence. CONCLUSIONS TAC is likely to be cost-effective (vs. CSA, in combination with AZA) at £20,000-30,000 per QALY. Analysis based on one RCT found BAS to be dominant, but analysis based on another RCT found BAS to be dominated. BAS plus TAC and AZA was predicted to be cost-effective at £20,000-30,000 per QALY when all regimens were compared using extrapolated adult evidence. High-quality primary effectiveness research is needed. The UK Renal Registry could form the basis for a prospective primary study. STUDY REGISTRATION This study is registered as PROSPERO CRD42014013544. FUNDING The National Institute for Health Research HTA programme.
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Affiliation(s)
- Marcela Haasova
- Peninsula Technology Assessment Group (PenTAG), Evidence Synthesis & Modelling for Health Improvement, University of Exeter, Exeter, UK
| | - Tristan Snowsill
- Peninsula Technology Assessment Group (PenTAG), Evidence Synthesis & Modelling for Health Improvement, University of Exeter, Exeter, UK
| | - Tracey Jones-Hughes
- Peninsula Technology Assessment Group (PenTAG), Evidence Synthesis & Modelling for Health Improvement, University of Exeter, Exeter, UK
| | - Louise Crathorne
- Peninsula Technology Assessment Group (PenTAG), Evidence Synthesis & Modelling for Health Improvement, University of Exeter, Exeter, UK
| | - Chris Cooper
- Peninsula Technology Assessment Group (PenTAG), Evidence Synthesis & Modelling for Health Improvement, University of Exeter, Exeter, UK
| | - Jo Varley-Campbell
- Peninsula Technology Assessment Group (PenTAG), Evidence Synthesis & Modelling for Health Improvement, University of Exeter, Exeter, UK
| | - Ruben Mujica-Mota
- Peninsula Technology Assessment Group (PenTAG), Evidence Synthesis & Modelling for Health Improvement, University of Exeter, Exeter, UK
| | - Helen Coelho
- Peninsula Technology Assessment Group (PenTAG), Evidence Synthesis & Modelling for Health Improvement, University of Exeter, Exeter, UK
| | - Nicola Huxley
- Peninsula Technology Assessment Group (PenTAG), Evidence Synthesis & Modelling for Health Improvement, University of Exeter, Exeter, UK
| | - Jenny Lowe
- Peninsula Technology Assessment Group (PenTAG), Evidence Synthesis & Modelling for Health Improvement, University of Exeter, Exeter, UK
| | - Jan Dudley
- Department of Paediatric Nephrology, Bristol Royal Hospital for Children (University Hospitals Bristol NHS Foundation Trust), Bristol, UK
| | - Stephen Marks
- Department of Paediatric Nephrology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK
| | - Chris Hyde
- Peninsula Technology Assessment Group (PenTAG), Evidence Synthesis & Modelling for Health Improvement, University of Exeter, Exeter, UK
| | - Mary Bond
- Peninsula Technology Assessment Group (PenTAG), Evidence Synthesis & Modelling for Health Improvement, University of Exeter, Exeter, UK
| | - Rob Anderson
- Peninsula Technology Assessment Group (PenTAG), Evidence Synthesis & Modelling for Health Improvement, University of Exeter, Exeter, UK
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17
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Hagemi A, Plumpton C, Hughes DA. Renal transplant patients' preference for the supply and delivery of immunosuppressants in Wales: a discrete choice experiment. BMC Nephrol 2017; 18:305. [PMID: 28969602 PMCID: PMC5625806 DOI: 10.1186/s12882-017-0720-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2016] [Accepted: 09/20/2017] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Prescribing policy recommendations aimed at moving immunosuppressant prescribing for renal transplant patients from primary to secondary care may result in benefits of increased safety and reduced cost. However, there is little evidence of patients' preferences for receiving their immunosuppressant therapy from hospitals compared to community dispensing. The aim of this study was to elicit patient preferences for different service configurations focusing in particular on home delivery versus collection of medication from hospital. METHODS A discrete choice experiment was administered to 265 renal transplant patients in North Wales. Respondents were presented 18 pairwise choices, labelled as either home delivery or hospital collection, and described by the attributes: frequency of supply, waiting time (for delivery or collection) and method of ordering (provider contact, patient contact via phone, patient contact electronically). Data were analysed using a random-effects logit model and marginal rates of substitution calculated based on the waiting time attribute. RESULTS A response rate of 63% was achieved, with 5332 usable observations from 150 respondents. Method of delivery (β coefficient 1.21; 95% confidence interval 1.05 to 1.38), frequency of supply (0.05; 0.03 to 0.08) waiting time (-0.00, -0.00 to -0.00), provider contact (desirable) (0.20; 0.12 to 0.27), patient contact by telephone (desirable) (0.09; 0.01 to 0.17) and patient contact electronically (undesirable) (-0.292; -0.37 to -0.21) were statistically significant (p < 0.05). Results indicate that patients are willing to increase waiting time by nearly 10 h to have a home delivery service. CONCLUSION Patients indicate a clear preference for a home delivery service. They prefer providers to make contact when new immunosuppressant supplies are required and show preference against ordering medication electronically. A policy for secondary care prescribing and hospital collection of medicines does not align with this preference.
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Affiliation(s)
- Anke Hagemi
- Betsi Cadwaladr University Health Board, Ysbyty Gwynedd, Bangor, Wales, UK
| | - Catrin Plumpton
- Centre for Health Economics and Medicines Evaluation, Bangor University, Ardudwy, Holyhead Road, Bangor, Wales, LL57 2PZ, UK
| | - Dyfrig A Hughes
- Centre for Health Economics and Medicines Evaluation, Bangor University, Ardudwy, Holyhead Road, Bangor, Wales, LL57 2PZ, UK.
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18
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O'Donoghue KJM, Reed RD, Knight SR, O'Callaghan JM, Ayaz‐Shah AA, Hassan S, Morris PJ, Pengel LHM. Systematic review of clinical practice guidelines in kidney transplantation. BJS Open 2017; 1:97-105. [PMID: 29951611 PMCID: PMC5989947 DOI: 10.1002/bjs5.17] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2017] [Accepted: 08/03/2017] [Indexed: 11/05/2022] Open
Abstract
BACKGROUND Clinical practice guidelines (CPGs) are widely used to inform the development of protocols for clinical management. Previous work has demonstrated that the quality of CPGs varies widely. This systematic review aimed to determine the quality of CPGs in kidney transplantation in the UK. METHODS CPGs in kidney transplantation published between 2010 and 2017 were identified through searches of MEDLINE, NHS NICE Evidence, and websites of relevant UK societies. Using the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool, three appraisers rated the quality of CPGs across six domains, the overall quality of each CPG, and whether it should be recommended for future use. Domain scores were calculated, and inter-rater reliability using the intraclass correlation coefficient (ICC) was reported. RESULTS Thirteen CPGs met the inclusion criteria. The domain 'clarity of presentation' scored highest, followed closely by 'scope and purpose'. The poorest scoring domains were 'applicability' and 'editorial independence'. Editorial independence also had the widest range of scores. Of the 13 CPGs, one was not recommended for future use, seven were recommended for use with modifications, and five for future use with no need for modification. Mean overall CPG quality was 5 (range 3-6) of a maximum score of 7, and mean inter-rater reliability was substantial with an ICC of 0·71. CONCLUSION UK CPGs scored satisfactorily, although with wide variation in how well each domain scored both within and across CPGs. The quality of UK CPGs can still be improved.
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Affiliation(s)
- K. J. M. O'Donoghue
- Centre for Evidence in Transplantation, Clinical Effectiveness UnitRoyal College of Surgeons of EnglandLondonUK
| | - R. D. Reed
- University of Alabama at BirminghamComprehensive Transplant InstituteBirmingham, AlabamaUSA
| | - S. R. Knight
- Centre for Evidence in Transplantation, Clinical Effectiveness UnitRoyal College of Surgeons of EnglandLondonUK
- Nuffield Department of Surgical SciencesUniversity of Oxford, John Radcliffe HospitalOxfordUK
| | - J. M. O'Callaghan
- Centre for Evidence in Transplantation, Clinical Effectiveness UnitRoyal College of Surgeons of EnglandLondonUK
- Nuffield Department of Surgical SciencesUniversity of Oxford, John Radcliffe HospitalOxfordUK
| | - A. A. Ayaz‐Shah
- Centre for Evidence in Transplantation, Clinical Effectiveness UnitRoyal College of Surgeons of EnglandLondonUK
| | - S. Hassan
- West London Renal and Transplant Centre, Hammersmith HospitalImperial College Healthcare NHS TrustLondonUK
| | - P. J. Morris
- Centre for Evidence in Transplantation, Clinical Effectiveness UnitRoyal College of Surgeons of EnglandLondonUK
- Nuffield Department of Surgical SciencesUniversity of Oxford, John Radcliffe HospitalOxfordUK
| | - L. H. M. Pengel
- Centre for Evidence in Transplantation, Clinical Effectiveness UnitRoyal College of Surgeons of EnglandLondonUK
- Nuffield Department of Surgical SciencesUniversity of Oxford, John Radcliffe HospitalOxfordUK
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Tacrolimus Blood Level Fluctuation Predisposes to Coexisting BK Virus Nephropathy and Acute Allograft Rejection. Sci Rep 2017; 7:1986. [PMID: 28512328 PMCID: PMC5434044 DOI: 10.1038/s41598-017-02140-1] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2016] [Accepted: 04/06/2017] [Indexed: 12/18/2022] Open
Abstract
BK virus nephropathy (BKVN) and allograft rejection are two distinct disease entities which occur at opposite ends of the immune spectrum. However, they coexist in renal transplant recipients. Predisposing factors for this coexistence remain elusive. We identified nine biopsy-proven BKVN patients with coexisting acute rejection, and 21 patients with BKVN alone. We retrospectively analyzed the dosage and blood concentrations of immunosuppressants during the 3-month period prior to the renal biopsy between the two patient groups. Compared to the BKVN alone group, renal function was noticeably worse in the coexistence group (p = 0.030). Regarding the dose and average drug level of immunosuppressants, there was no difference between the two groups. Interestingly, the coefficient of variance of tacrolimus trough blood level was noticeably higher during the 3-month period prior to the renal biopsy in the coexistence group (p = 0.010). Our novel findings suggest that a higher variability of tacrolimus trough level may be associated with the coexistence of BKVN and acute rejection. Since the prognosis is poor and the treatment is challenging in patients with coexisting BKVN and acute rejection, transplant clinicians should strive to avoid fluctuations in immunosuppressant drug levels in patients with either one of these two disease entities.
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20
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Wadström J, Ericzon BG, Halloran PF, Bechstein WO, Opelz G, Serón D, Grinyó J, Loupy A, Kuypers D, Mariat C, Clancy M, Jardine AG, Guirado L, Fellström B, O'Grady J, Pirenne J, O'Leary JG, Aluvihare V, Trunečka P, Baccarani U, Neuberger J, Soto-Gutierrez A, Geissler EK, Metzger M, Gray M. Advancing Transplantation: New Questions, New Possibilities in Kidney and Liver Transplantation. Transplantation 2017; 101 Suppl 2S:S1-S41. [PMID: 28125449 DOI: 10.1097/tp.0000000000001563] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Affiliation(s)
- Jonas Wadström
- 1 Karolinska University Hospital, Stockholm, Sweden. 2 Karolinska Institutet, Stockholm, Sweden. 3 Alberta Transplant Applied Genomics Centre, Edmonton, Canada. 4 Frankfurt University Hospital and Clinics, Frankfurt, Germany. 5 University of Heidelberg, Heidelberg, Germany. 6 Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain. 7 Red de Investigación Renal (REDinREN), Instituto Carlos III, Madrid, Spain. 8 Hospital Universitari de Bellvitge, University of Barcelona, Spain. 9 Service de Néphrologie-Transplantation, Hôpital Necker, Paris, France. 10 University Hospitals Leuven, Leuven, Belgium. 11 University Hospital of Saint-Etienne, Jean Monnet University, France. 12 Western Infirmary, Glasgow, United Kingdom. 13 Fundació Puigvert, Barcelona, Spain. 14 University of Uppsala, Uppsala, Sweden. 15 King's College Hospital, London, United Kingdom. 16 Baylor University Medical Center Dallas, Dallas, TX. 17 Transplantcenter, Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic. 18 Department of Medical and Biological Sciences, University Hospital of Udine, Udine, Italy. 19 Liver Unit, Queen Elizabeth Hospital, Birmingham, United Kingdom. 20 Directorate of Organ Donation and Transplantation, NHS Blood and Transplant, Bristol, United Kingdom. 21 Department of Pathology, University of Pittsburgh, Pittsburgh, PA. 22 Experimental Surgery, University Hospital Regensburg, University of Regensburg, Regensburg, Germany. 23 Ahead of Time GmbH, Starnberg, Germany. 24 Better Value Healthcare, Oxford, United Kingdom
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21
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Baraldo M. Meltdose Tacrolimus Pharmacokinetics. Transplant Proc 2017; 48:420-3. [PMID: 27109969 DOI: 10.1016/j.transproceed.2016.02.002] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2015] [Revised: 01/31/2016] [Accepted: 02/02/2016] [Indexed: 11/25/2022]
Abstract
BACKGROUND Nonadherence to immunosuppressive therapy contributes to the loss of grafts. One of the problem is the fractioning of immunosuppressive dose. In fact, it was demonstrated that a single daily dose (QD) is associated with an increased adherence to therapy compared with twice daily dosing (BID). Tacrolimus (TAC), calcineurin inhibitor, is one of immunosuppression pillar in organ transplantation and its action is strongly correlated with blood concentration and therefore the therapeutic drug monitoring is recommended in the guidelines. However, one of the critical points of TAC is the poor and variable bioavailability that influences immunosuppression, and is also responsible for adverse effects. METHODS MeltDose® Technology is a new technology to improve efficacy and/or reduce side effects. This new technology applied to TAC (Envarsus® or LCP-TAC) has achieved 4 main objectives: (1) improved bioavailability, (2) reduced dose fractioning to one tablet per day, (3) limited variability concentrations of TAC, and (4) lower doses of TAC will be administered. RESULTS We analyzed the pharmacokinetic profile, efficacy, and security of Envarsus®.
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Affiliation(s)
- M Baraldo
- Department of Experimental and Clinical Medicine, Medical School, University of Udine; SOC Institute of Clinical Pharmacology, University-Hospital S. Maria della Misercordia, Udine, Italy.
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22
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Acuna SA, Huang JW, Scott AL, Micic S, Daly C, Brezden-Masley C, Kim SJ, Baxter NN. Cancer Screening Recommendations for Solid Organ Transplant Recipients: A Systematic Review of Clinical Practice Guidelines. Am J Transplant 2017; 17:103-114. [PMID: 27575845 DOI: 10.1111/ajt.13978] [Citation(s) in RCA: 141] [Impact Index Per Article: 17.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2016] [Accepted: 07/13/2016] [Indexed: 01/25/2023]
Abstract
Solid organ transplant recipients (SOTRs) are at increased risk of developing and dying from cancer. However, controversies exist around cancer screening in this population owing to reduced life expectancy and competing causes of death. This systematic review assesses the availability, quality and consistency of cancer screening recommendations in clinical practice guidelines (CPGs). We systematically searched bibliographic databases and gray literature to identify CPGs and assessed their quality using AGREE II. Recommendations were extracted along with their supporting evidence. Thirteen guidelines were included in the review. CPGs for kidney recipients were the most frequent source of screening recommendations, and recommendations for skin cancer screening were most frequently presented. Some screening recommendations differed from those for the general population, based on literature demonstrating higher cancer incidence among SOTRs versus direct evidence of screening effectiveness. Relevant stakeholders such as oncology specialists, primary care providers and public health experts were not involved in the formulation of the screening recommendations. In conclusion, although several guidelines make recommendations for cancer screening in SOTRs, the availability of cancer screening recommendations varied considerably by transplanted organ. More studies are required to inform cancer screening recommendations in SOTRs, and guideline development should involve transplant patients, oncologists and cancer screening specialists.
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Affiliation(s)
- S A Acuna
- Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada.,Department of Surgery, Li Ki Shing Knowledge Institute, St. Michael's Hospital, Toronto, Canada
| | - J W Huang
- Department of Surgery, Li Ki Shing Knowledge Institute, St. Michael's Hospital, Toronto, Canada
| | - A L Scott
- Department of Surgery, Li Ki Shing Knowledge Institute, St. Michael's Hospital, Toronto, Canada
| | - S Micic
- Department of Surgery, Li Ki Shing Knowledge Institute, St. Michael's Hospital, Toronto, Canada
| | - C Daly
- Department of Surgery, Li Ki Shing Knowledge Institute, St. Michael's Hospital, Toronto, Canada
| | - C Brezden-Masley
- Division of Hematology/Oncology, St. Michael's Hospital, Toronto, Canada.,Department of Medicine, University of Toronto, Toronto, Canada
| | - S J Kim
- Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada.,Department of Medicine, University of Toronto, Toronto, Canada.,Division of Nephrology and the Kidney Transplant Program, Toronto General Hospital, University Health Network, Toronto, Canada
| | - N N Baxter
- Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada.,Department of Surgery, Li Ki Shing Knowledge Institute, St. Michael's Hospital, Toronto, Canada.,Division of General Surgery, Department of Surgery, University of Toronto, Toronto, Canada
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23
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Dobrowolski LC, van Huis M, van der Lee JH, Peters Sengers H, Liliën MR, Cransberg K, Cornelissen M, Bouts AH, de Fijter JW, Berger SP, van Zuilen A, Nurmohamed SA, Betjes MH, Hilbrands L, Hoitsma AJ, Bemelman FJ, Krediet P, Groothoff JW. Epidemiology and management of hypertension in paediatric and young adult kidney transplant recipients in The Netherlands. Nephrol Dial Transplant 2016; 31:1947-1956. [DOI: 10.1093/ndt/gfw225] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2015] [Accepted: 04/18/2016] [Indexed: 12/16/2022] Open
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24
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Kinsella S, Murphy K, Breen M, O'Neill S, McLaughlin P, Coyle J, Bogue C, O'Neill F, Moore N, McGarrigle A, Molloy MG, Maher MM, Eustace JA. Comparison of single CT scan assessment of bone mineral density, vascular calcification and fat mass with standard clinical measurements in renal transplant subjects: the ABC HeART study. BMC Nephrol 2015; 16:188. [PMID: 26558994 PMCID: PMC4642694 DOI: 10.1186/s12882-015-0182-6] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2015] [Accepted: 11/02/2015] [Indexed: 12/01/2022] Open
Abstract
Background Despite limitations of routine methods, Clinical Practice Guidelines support the assessment of bone mineral density (BMD) and vascular calcification in renal transplant recipients. Changes in fat mass also occur post-transplantation, although they are traditionally difficult to measure accurately. We report the feasibility, convenience and accuracy of measuring the above 3 parameters using a novel CT protocol. Methods We conducted a cross-sectional study of 64 first renal allograft recipients (eGFR > 30 ml/min/1.73 m2). Quantitative CT (QCT) BMD analysis was conducted using CT lumbar spine (GE Medical Systems Lightspeed VCT & Mindways QCT Pro Bone Mineral Densitometry System Version 4.2.3) to calculate spinal volumetric BMD and compared with standard DXA calculated areal BMD at the spine, hip and distal forearm. Abdominal aortic calcification was assessed by semi-quantitative Aortic Calcification Index (ACI) method and compared with lateral lumbar x-ray Kappuila score and pulse wave velocity (PWV). Visceral and subcutaneous adipose tissue volume (Osirix 16 Ver 3.7.1) was compared with BMI. Results Participants were 61 % male, had a mean age of 47 years, median ESKD duration of 5.4 years and a mean eGFR of 54 ml/min. iDXA median T-score at proximal femur was −1.2 and at lumbar spine was −0.2. Median QCT Trabecular T-score at lumbar spine was −1.2. The percent of subjects with a T-score of <2.5 by site and method was DXA Proximal Femur: 7 %, DXA distal radius: 17 %, DXA spine: 9 %, QCT (American College of Radiology cutoffs): 9 %. CT derived ACI correlated with PWV (r = 0.29, p = 0.02), pulse wave pressure (r = 0.51, p < 0.001), QCT Trabecular (−0.31, p = 0.01) and cortical volumetric BMD and history of cardiovascular events (Mann–Whitney U, p = 0.02). Both visceral and subcutaneous adipose tissue correlated with BMI (r = 0.63 & 0.64, p < 0.001). Conclusions Single CT scan triple assessment of BMD, vascular calcification and body composition is an efficient, accurate and convenient method of risk factor monitoring post renal transplantation.
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Affiliation(s)
- Sinead Kinsella
- Department of Renal Medicine, Cork University Hospital, Cork, Ireland. .,HRB Clinical Research Facility at UCC, 2nd Floor, Mercy University Hospital, Grenville Place, Cork, Ireland.
| | - Kevin Murphy
- Department of Radiology, Cork University Hospital, Cork, Ireland.
| | - Micheal Breen
- Department of Radiology, Cork University Hospital, Cork, Ireland.
| | - Siobhan O'Neill
- Department of Radiology, Cork University Hospital, Cork, Ireland.
| | | | - Joe Coyle
- Department of Radiology, Cork University Hospital, Cork, Ireland.
| | - Conor Bogue
- Department of Radiology, Cork University Hospital, Cork, Ireland.
| | - Fiona O'Neill
- Department of Radiology, Cork University Hospital, Cork, Ireland.
| | - Niamh Moore
- Department of Radiology, Cork University Hospital, Cork, Ireland.
| | | | - Michael G Molloy
- Department of Rheumatology, Cork University Hospital, Cork, Ireland.
| | - Michael M Maher
- Department of Radiology, Cork University Hospital, Cork, Ireland.
| | - Joseph A Eustace
- Department of Renal Medicine, Cork University Hospital, Cork, Ireland. .,HRB Clinical Research Facility at UCC, 2nd Floor, Mercy University Hospital, Grenville Place, Cork, Ireland.
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25
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Mitsides N, Greenan K, Green D, Middleton R, Lamerton E, Allen J, Redshaw J, Chadwick PR, Subudhi CP, Wood G. Complications and outcomes of trimethoprim-sulphamethoxazole as chemoprophylaxis for pneumocystis pneumonia in renal transplant recipients. Nephrology (Carlton) 2015; 19:157-63. [PMID: 24387294 DOI: 10.1111/nep.12201] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/23/2013] [Indexed: 12/11/2022]
Abstract
BACKGROUND Following a pneumocystis pneumonia (PCP) outbreak in our nephrology unit, all transplant patients were offered chemoprophylaxis with trimethoprim-sulphamethoxazole (TMP-SMX) as the first line agent. A high rate of complications was noted. We aimed to quantify TMP-SMX associated adverse events and evaluate its prophylactic benefit in their light. Potential risk factors for complications' development were also investigated. METHOD This was an observational study of outcomes in transplant recipients commenced on TMP-SMX prophylaxis for 1year period. End-points were adverse events due to TMP-SMX, the additional medical burden resulting from these events, and PCP diagnosis. RESULTS 290 patients commenced on TMP-SMX. 110 (38%) developed complications with most common being rise in serum creatinine (Cr) (n = 63, 22%) followed by gastrointestinal symptoms (n = 15, 5%), and leucopenia (n = 5, 2%). PCP incidence fell from 19 cases in 19 months to 2 cases in 12 months. Baseline renal function (P = 0.019) was an independent predictors for developing rise in Cr with TMP-SMX. CONCLUSION Use of chemoprophylaxis is an effective strategy in dealing with a PCP outbreak but can lead to a high number of complications. Rises in serum Cr can cause significant concern and increase in the number of investigations.
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Affiliation(s)
- Nicos Mitsides
- Nephrology Department, Salford Royal NHS Foundation Trust, Salford, UK
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26
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Zhang Q, Liu YF, Su ZX, Shi LP, Chen YH. Serum fractalkine and interferon-gamma inducible protein-10 concentrations are early detection markers for acute renal allograft rejection. Transplant Proc 2015; 46:1420-5. [PMID: 24935307 DOI: 10.1016/j.transproceed.2014.02.019] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2013] [Revised: 01/23/2014] [Accepted: 02/27/2014] [Indexed: 11/25/2022]
Abstract
OBJECTIVE The aims of this study were to determine if characterization of serum concentrations of interferon-gamma inducible protein-10 (IP-10), fractalkine, and their receptors (CXCR3 and CX3CR1) were predictive of acute allograft rejection in kidney transplant recipients. METHODS Kidney transplant recipients (n = 52) were enrolled in this study and divide into either the acute rejection (AR, n = 15) or non-acute rejection (NAR, n = 35) groups. Serum samples from recipients were collected 1 day prior to transplantation and on days 1, 3, 5, 7, and 9 post-transplantation. The accuracy of chemokine concentrations for predicting acute rejection episodes was evaluated using receiver operator characteristic (ROC) curves. RESULTS AR was diagnosed in 15 patients based on histologic changes to renal biopsies. AR patients had significantly higher serum fractalkine, CXCR1, IP-10, and CXCR3 levels compared to levels observed in the NAR group and healthy controls. Fractalkine and IP-10 had the largest area under the ROC curve at 0.86 (95% confidence interval: 0.77-0.96). Following steroid therapy, chemokine levels decreased, which may serve to predict the therapeutic response to steroid therapy. CONCLUSION Measuring serum levels of fractalkine, IP-10, and their receptors (especially the fractalkine/IP-10 combination) may serve as a noninvasive approach for the early diagnosis of renal allograft rejection.
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Affiliation(s)
- Q Zhang
- Department of Urinary Surgery, the First Affiliated Hospital of Jinan University Guangzhou, Guangdong, China
| | - Y-F Liu
- Department of Urinary Surgery, the First Affiliated Hospital of Jinan University Guangzhou, Guangdong, China
| | - Z-X Su
- Department of Urinary Surgery, the First Affiliated Hospital of Jinan University Guangzhou, Guangdong, China.
| | - L-P Shi
- Department of Urinary Surgery, the First Affiliated Hospital of Jinan University Guangzhou, Guangdong, China
| | - Y-H Chen
- Department of Urinary Surgery, the First Affiliated Hospital of Jinan University Guangzhou, Guangdong, China
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27
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Tacrolimus Prolonged Release (Envarsus®): A Review of Its Use in Kidney and Liver Transplant Recipients. Drugs 2015; 75:309-20. [DOI: 10.1007/s40265-015-0349-2] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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28
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Murray EC, McMillan M. Long-term outcomes of patients on the 1988 West of Scotland renal transplant waiting list. Scott Med J 2014; 60:32-6. [PMID: 25475974 DOI: 10.1177/0036933014563238] [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: 11/17/2022]
Abstract
BACKGROUND The prevalent population with established renal failure continues to grow. METHOD Using the Renal Electronic Patient Record, we assess the long-term outcomes of the adult population in the West of Scotland who were awaiting kidney transplantation in 1988 (n = 219), and compare the demographics to the 2011 transplant waiting list (n = 409). RESULTS Comparing the 2011 transplant waiting list, there are now more patients, but they are older, more likely to be female, and are more likely to have diabetes as a cause of renal failure. Seventy-four percent received a transplant; of these, 41% of the transplants ultimately failed and the patient returned to dialysis; 39% of patients died with a functioning graft and 20% remain alive with continuing transplant function. Life expectancy for those with renal failure was less than 60 years, significantly lower than the general population, though 29% survived for 20 years, half of these with a functioning kidney transplant and half having returned to dialysis. CONCLUSION As survival with a transplant improves, attention is required to reduce the causes of mortality, in particular cardiovascular disease, and malignancy and infection associated with immunosuppression.
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Affiliation(s)
- Eleanor C Murray
- Renal ST4 (LAT), Glasgow Renal and Transplant Unit, Western Infirmary, UK
| | - Margaret McMillan
- Consultant Renal Physician, Glasgow Renal and Transplant Unit, Western Infirmary, UK
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29
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Ryan KJ, Casas JMS, Mash LE, McLellan SL, Lloyd LE, Stinear JW, Plank LD, Collins MG. The effect of intensive nutrition interventions on weight gain after kidney transplantation: protocol of a randomised controlled trial. BMC Nephrol 2014; 15:148. [PMID: 25204676 PMCID: PMC4176865 DOI: 10.1186/1471-2369-15-148] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2014] [Accepted: 09/02/2014] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Weight gain and obesity are common after kidney transplantation, particularly during the first year. Obesity is a risk factor for the development of new-onset diabetes after transplantation, and is associated with reduced graft survival. There is a lack of evidence for effective interventions to prevent weight gain after kidney transplantation. METHODS/DESIGN The effect of INTEnsive Nutrition interventions on weight gain after kidney Transplantation (INTENT) trial is a single-blind (outcomes assessor), randomised controlled trial to assess the effect of intensive nutrition interventions, including exercise advice, on weight gain and metabolic parameters in the first year after transplantation. Participants will be randomised during the first post-transplant month to either standard care (four visits with a renal dietitian over twelve months) or intensive nutrition intervention (eight visits with a renal dietitian over the first six months, four visits over the second six months, and three visits over the first six months with an exercise physiologist). In the intensive intervention group, nutrition counselling will be provided using motivational interviewing techniques to encourage quality engagement. Collaborative goal setting will be used to develop personalised nutrition care plans. Individualised advice regarding physical activity will be provided by an exercise physiologist. The primary outcome of the study is weight at six months after transplant, adjusted for baseline (one month post-transplant) weight, obesity and gender. Secondary outcomes will include changes in weight and other anthropometric measures over 12 months, body composition (in vivo neutron activation analysis, total body potassium, dual-energy X-ray absorptiometry, and bioelectrical impedance), biochemistry (fasting glucose, lipids, haemoglobin A1c and insulin), dietary intake and nutritional status, quality of life, and physical function. DISCUSSION There are currently few randomised clinical trials of nutrition interventions after kidney transplantation. The INTENT trial will thus provide important data on the effect of intensive nutrition interventions on weight gain after transplant and the associated metabolic consequences. Additionally, by assessing changes in glucose metabolism, the study will also provide data on the feasibility of undertaking larger multi-centre trials of nutrition interventions to reduce the incidence or severity of diabetes after transplantation. TRIAL REGISTRATION Australian New Zealand Clinical Trials Registry Number: ACTRN12614000155695.
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Affiliation(s)
| | | | | | | | | | | | | | - Michael G Collins
- Department of Renal Medicine, Auckland City Hospital, Auckland District Health Board, Private Bag 92024, Auckland 1142, New Zealand.
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30
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Stoumpos S, Jardine AG, Mark PB. Cardiovascular morbidity and mortality after kidney transplantation. Transpl Int 2014; 28:10-21. [PMID: 25081992 DOI: 10.1111/tri.12413] [Citation(s) in RCA: 150] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2014] [Accepted: 07/28/2014] [Indexed: 12/14/2022]
Abstract
Kidney transplantation is the optimal treatment for patients with end stage renal disease (ESRD) who would otherwise require dialysis. Patients with ESRD are at dramatically increased cardiovascular (CV) risk compared with the general population. As well as improving quality of life, successful transplantation accords major benefits by reducing CV risk in these patients. Worldwide, cardiovascular disease remains the leading cause of death with a functioning graft and therefore is a leading cause of graft failure. This review focuses on the mechanisms underpinning excess CV morbidity and mortality and current evidence for improving CV risk in kidney transplant recipients. Conventional CV risk factors such as hypertension, diabetes mellitus, dyslipidaemia and pre-existing ischaemic heart disease are all highly prevalent in this group. In addition, kidney transplant recipients exhibit a number of risk factors associated with pre-existing renal disease. Furthermore, complications specific to transplantation may ensue including reduced graft function, side effects of immunosuppression and post-transplantation diabetes mellitus. Strategies to improve CV outcomes post-transplantation may include pharmacological intervention including lipid-lowering or antihypertensive therapy, optimization of graft function, lifestyle intervention and personalizing immunosuppression to the individual patients risk profile.
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31
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Evans R, Bhagani S, Haque T, Harber M. Infectious Complications of Transplantation. PRACTICAL NEPHROLOGY 2014. [PMCID: PMC7121279 DOI: 10.1007/978-1-4471-5547-8_71] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
Post-transplant infection is a common cause of graft deterioration, morbidity and mortality. It is also responsible for delayed discharge, multiple, often prolonged admissions and thus a significant clinical challenge. Infections can be donor derived, pre-existing in the recipient, nosocomial and opportunistic. For each of these categories, it is often possible to significantly reduce hazard and thus the adverse consequences by first identifying patients at high risk. As always, clinical vigilance is vital, but equally important is the establishment of robust clinical systems for prevention, screening and rapid treatment.
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