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Zuckerman J, Pham PT, Parakkal M, Velazquez AF, Sarkar M, Pablos MA, Bunnapradist S, Lum EL. C3 glomerulopathy post kidney transplantation: A single center experience. World J Transplant 2025; 15:101517. [DOI: 10.5500/wjt.v15.i2.101517] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Revised: 11/08/2024] [Accepted: 12/25/2024] [Indexed: 02/21/2025] Open
Abstract
BACKGROUND C3 glomerulopathies (C3G) are a rare cause of kidney failure resulting from complement dysregulation. Small studies demonstrate a high rate of recurrence and poor outcomes in kidney transplantation. Treatment efficacy in this setting with eculizumab, a terminal complement inhibitor, is largely unknown.
AIM To determine the outcomes of kidney transplantation in patients with C3G and the potential impact of eculizumab.
METHODS We retrospectively studied kidney transplant recipients who underwent a post-transplant biopsy confirming C3G between January 1, 1993 and December 31, 2023 at a single center. Only the first episode of kidney transplant was reviewed. The electronic medical records were reviewed for post-transplant allograft function, indication for biopsy, time to biopsy from transplant, time to allograft failure from transplantation, post-C3G treatment, complement laboratory testing, and concurrent malignancy/infection. Reports, and when available slides and immunofluorescence/electron microscopic images, were re-reviewed by a renal pathologist.
RESULTS A total of fifteen patients were included in this study. Fourteen patients had suspected recurrent disease, with a pre-transplant native kidney report of C3G. One patient developed de novo C3G. Median post kidney transplant clinical follow up time was 91 months. Median time to recurrence was 7 months with median graft survival of 48 months post kidney transplantation. The most common index biopsy pattern of injury was endocapillary proliferative glomerulonephritis (often with exudative features) with or without mesangial hypercellularity (56%) followed by membranoproliferative glomerulonephritis (25%). Most patients developed membranoproliferative glomerulonephritis pattern of injury on follow up biopsies (63%). Seven patients with recurrent disease received treatment with eculizumab with a median graft survival of 73 months, with five functioning grafts by the end of the study period. Seven patients with recurrent disease did not receive therapy, and all lost their graft with a median graft survival of 22 months (P = 0.003).
CONCLUSION C3G following kidney transplantation is mostly a recurrent disorder with a poor prognosis in untreated patients. Untreated recurrence has a poor prognosis with median allograft survival < 2 years. Early treatment with eculizumab may improve transplant outcomes in patients with recurrent C3G.
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Affiliation(s)
- Jonathan Zuckerman
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, United States
| | - Phuong-Thu Pham
- Department of Medicine, Division of Nephrology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, United States
| | - Meena Parakkal
- Department of Medicine, Division of Nephrology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, United States
| | - Alexis F Velazquez
- Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, United States
| | - Mrinalini Sarkar
- Department of Medicine, Division of Nephrology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, United States
| | - Michael A Pablos
- Division of Nephrology, Harbor Medical Center, University of California, Los Angeles, CA 90095, United States
| | - Suphamai Bunnapradist
- Department of Medicine, Division of Nephrology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, United States
| | - Erik L Lum
- Department of Medicine, Division of Nephrology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, United States
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Oruc A, Ersoy A, Ozkalemkas F, Gul CB, Yigit E, Yildiz A. Utilization and importance of timing of therapeutic plasma exchange in kidney transplantation: A single-center experience. Ther Apher Dial 2025; 29:516-524. [PMID: 40037344 DOI: 10.1111/1744-9987.70002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Revised: 02/06/2025] [Accepted: 02/17/2025] [Indexed: 03/06/2025]
Abstract
INTRODUCTION Therapeutic plasma exchange (TPE) is a prominent approach for specific conditions among renal transplant candidates and recipients. The indications of TPE, those related to kidney transplantation, are limited, and knowledge and utilization strategies are blurred. Herein, we aimed to review our clinical experience of TPE among renal transplant recipients. METHODS A total of 69 (40.22 ± 12.29 years, 40 males, 63.8% deceased donor) ABO blood type-compatible kidney transplant recipients who underwent TPE were evaluated between January 2013 and December 2019. RESULTS A median of 5 (IQR 4-7) TPE sessions was administered at a median duration of 31 (IQR 3-564) days after transplantation. The main indication was a rejection episode. A total of 61 (39.44 ± 12.22 years, 24 living donor, 10 re-transplant, 37 male) recipients were successfully discharged with a serum creatinine of 1.39 (IQR 1-1.91) mg/dL, and eGFR of 62 (IQR 39-94) ml/min. Comparing the recipients according to TPE timing, early administered 32 (52.5%) recipients with a median of 4 (IQR 4-7) days after transplantation had better graft survival (62.5% vs. 17.2%, p < 0.001), despite higher mortality rates (25% vs.10%, p < 0.001). The rate of graft loss was higher (62.1% vs. 9.4%, p < 0.001) among the recipients who required TPE during the late post-transplant period (756 [IQR 272-1307] days). CONCLUSION According to our findings, TPE could provide beneficial effects on graft and patient outcomes, and the timing of TPE could influence its efficiency. Further studies are needed to support our findings.
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Affiliation(s)
- Aysegul Oruc
- Division of Nephrology, Bursa Uludag University Faculty of Medicine, Bursa, Turkey
| | - Alparslan Ersoy
- Division of Nephrology, Bursa Uludag University Faculty of Medicine, Bursa, Turkey
| | - Fahir Ozkalemkas
- Division of Haematology, Bursa Uludag University Faculty of Medicine, Bursa, Turkey
| | - Cuma Bulent Gul
- Division of Nephrology, Bursa Uludag University Faculty of Medicine, Bursa, Turkey
| | - Elif Yigit
- Department of Internal Medicine, Bursa Uludag University Faculty of Medicine, Bursa, Turkey
| | - Abdulmecit Yildiz
- Division of Nephrology, Bursa Uludag University Faculty of Medicine, Bursa, Turkey
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Attieh RM, Bharati J, Sharma P, Nair G, Ayehu G, Jhaveri KD. Kidney transplant in patients with C3 glomerulopathy. Clin Kidney J 2025; 18:sfaf134. [PMID: 40385590 PMCID: PMC12082085 DOI: 10.1093/ckj/sfaf134] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2025] [Indexed: 05/20/2025] Open
Abstract
Complement protein 3 (C3) glomerulopathy (C3G) is a rare and progressive kidney disease primarily affecting young individuals and frequently advancing to end-stage kidney disease (ESKD). For ESKD, kidney transplantation remains the optimal treatment option; however, C3G has a high recurrence rate post-transplantation, affecting over two-thirds of transplanted patients. Despite advances in our understanding of C3G, significant gaps persist regarding the optimal timing for transplantation and the best strategies for peri-transplant management. Currently, no clear evidence links functional complement levels to the risk of post-transplant recurrence. Genetic counseling is also complex, due to variable gene penetrance and weak genotype-phenotype correlations, which limit predictive accuracy. Transplant-related factors are believed to significantly influence C3G recurrence, yet there are no established methods for preventing recurrence after transplantation. Eculizumab has shown inconsistent efficacy in managing recurrent C3G. However, new proximal complement inhibitors, such as factor B and C3 inhibitors, are under investigation in clinical trials and show promise. Some of these trials include kidney transplant patients with C3G, and their outcomes could potentially shape future treatment protocols.
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Affiliation(s)
| | - Joyita Bharati
- Section of Nephrology, Boston Medical Center and Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA
| | - Purva Sharma
- Division of Kidney Disease and Hypertension, Glomerular Center at Northwell Health, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Great Neck, NY, USA
| | - Gayatri Nair
- Division of Kidney Disease and Hypertension, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Manhasset, NY, USA
| | - Gashu Ayehu
- Division of Kidney Disease and Hypertension, Glomerular Center at Northwell Health, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Great Neck, NY, USA
| | - Kenar D Jhaveri
- Division of Kidney Disease and Hypertension, Glomerular Center at Northwell Health, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Great Neck, NY, USA
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Meier RPH, Pierson RN, Fishman JA, Buhler LH, Bottino R, Ladowski JM, Ekser B, Wolf E, Brenner P, Ierino F, Mohiuddin M, Cooper DKC, Hawthorne WJ. International Xenotransplantation Association (IXA) Position Paper on Kidney Xenotransplantation. Transplantation 2025:00007890-990000000-01051. [PMID: 40197435 DOI: 10.1097/tp.0000000000005372] [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: 04/10/2025]
Abstract
Porcine kidney xenotransplantation for end-stage renal disease (ESRD) has reached the stage of clinical testing following major advances in donor pig genetic modifications and effective immunosuppressive strategies through decades of rigorous translational research. Reports of pig kidney xenograft survival beyond 1 year post-transplant in nonhuman primate (NHP) models justify optimism for its potential as an alternative to allotransplantation. In the United States, experimental transplantations of genetically engineered (GE) porcine kidneys into brain-dead subjects and a small number of ESRD patients have shown no evidence of hyperacute rejection and adequate pig kidney function for up to several months. Here we discuss pre-clinical/clinical results, infectious disease, ethical, and regulatory considerations, and propose evidence-based recommendations. For initial clinical trials in kidney xenotransplantation, we make the following recommendations: (i) transplantation with organs from a triple knockout (TKO) donor pig, preferably with added human transgenes, (ii) an immunosuppressive regimen with induction therapy to deplete T (and possibly B) cells, and maintenance therapy based on a cluster of differentiation (CD)40/CD154 co-stimulation pathway blockade, (iii) the patient should be fully acceptable as a candidate for allotransplantation but should be unlikely ever to receive an allograft. Patients aged 60-69 years (extendable to 40-75 years, if one of the criteria mentioned below is present), of blood group B or O, and with diabetes are most at risk in this regard. Other patients who could be considered are (i) those who have lost two or more previous kidney allografts from recurrent disease in the graft, (ii) those with broad human leukocyte antigen (HLA)-reactivity but no evidence of anti-pig antibodies, including swine leukocyte antigen (SLA), and (iii) those with failing vascular access. Clinical pilot studies in carefully and highly selected patients with no alternative therapy will provide the foundation upon which to base subsequent formal expanded clinical trials.
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Affiliation(s)
- Raphael P H Meier
- Department of Surgery, University of Maryland School of, Medicine, Baltimore, MD
| | - Richard N Pierson
- Division of Cardiac Surgery and Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, MA
| | - Jay A Fishman
- Transplantation Infectious Disease Program and Massachusetts General Hospital Transplant Center, Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA
| | - Leo H Buhler
- Cantonal Hospital Fribourg, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland
| | - Rita Bottino
- Allegheny Health Network, Carnegie Mellon University, Pittsburgh, PA
| | - Joseph M Ladowski
- Department of Surgery, Duke University School of Medicine, Durham, NC
| | - Burcin Ekser
- Division of Abdominal Transplant Surgery, Stritch School of Medicine, Loyola University Chicago, Maywood, IL
| | | | - Paolo Brenner
- Department of Cardiac Surgery, University Hospital, LMU Munich, Munich, Germany
| | - Francesco Ierino
- Department of Nephrology and Transplantation, St Vincent's Hospital, University of Melbourne, Fitzroy, VIC, Australia
| | - Muhammad Mohiuddin
- Cardiac Xenotransplantation Program, University of Maryland School of Medicine, Baltimore, MD
| | - David K C Cooper
- Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital/Harvard Medical School, Boston, MA
| | - Wayne J Hawthorne
- The Department of Surgery, University of Sydney, Westmead Hospital, Westmead, NSW, Australia
- The Centre for Transplant & Renal Research, The Westmead Institute for Medical Research, Westmead, NSW, Australia
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5
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Meier RPH, Pierson RN, Fishman JA, Buhler LH, Bottino R, Ladowski JM, Ekser B, Wolf E, Brenner P, Ierino F, Mohiuddin M, Cooper DKC, Hawthorne WJ. International Xenotransplantation Association (IXA) Position Paper on Kidney Xenotransplantation. Xenotransplantation 2025; 32:e70003. [PMID: 40198240 DOI: 10.1111/xen.70003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Accepted: 10/12/2024] [Indexed: 04/10/2025]
Abstract
Porcine kidney xenotransplantation for end-stage renal disease (ESRD) has reached the stage of clinical testing following major advances in donor pig genetic modifications and effective immunosuppressive strategies through decades of rigorous translational research. Reports of pig kidney xenograft survival beyond 1 year posttranplant in nonhuman primate (NHP) models justify optimism for its potential as an alternative to allotransplantation. In the United States, experimental transplantations of genetically engineered (GE) porcine kidneys into brain-dead subjects and a small number of ESRD patients have shown no evidence of hyperacute rejection and adequate pig kidney function for up to several months. Here we discuss pre-clinical/clinical results, infectious disease, ethical, and regulatory considerations, and propose evidence-based recommendations. For initial clinical trials in kidney xenotransplantation, we make the following recommendations: (i) transplantation with organs from a triple knockout (TKO) donor pig, preferably with added human transgenes, (ii) an immunosuppressive regimen with induction therapy to deplete T (and possibly B) cells, and maintenance therapy based on a cluster of differentiation (CD)40/CD154 co-stimulation pathway blockade, (iii) the patient should be fully acceptable as a candidate for allotransplantation but should be unlikely ever to receive an allograft. Patients aged 60-69 years (extendable to 40-75 years, if one of the criteria mentioned below is present), of blood group B or O, and with diabetes are most at risk in this regard. Other patients who could be considered are (i) those who have lost two or more previous kidney allografts from recurrent disease in the graft, (ii) those with broad human leukocyte antigen (HLA)-reactivity but no evidence of anti-pig antibodies, including swine leukocyte antigen (SLA), and (iii) those with failing vascular access. Clinical pilot studies in carefully and highly selected patients with no alternative therapy will provide the foundation upon which to base subsequent formal expanded clinical trials.
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Affiliation(s)
- Raphael P H Meier
- Department of Surgery, University of Maryland School of, Medicine, Baltimore, Maryland, USA
| | - Richard N Pierson
- Division of Cardiac Surgery and Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Jay A Fishman
- Transplantation Infectious Disease Program and Massachusetts General Hospital Transplant Center, Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Leo H Buhler
- Cantonal Hospital Fribourg, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland
| | - Rita Bottino
- Allegheny Health Network, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA
| | - Joseph M Ladowski
- Department of Surgery, Duke University School of Medicine, Durham, North Carolina, USA
| | - Burcin Ekser
- Division of Abdominal Transplant Surgery, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois, USA
| | | | - Paolo Brenner
- Department of Cardiac Surgery, University Hospital, LMU Munich, Munich, Germany
| | - Francesco Ierino
- Department of Nephrology and Transplantation, St Vincent's Hospital, University of Melbourne, Fitzroy, VIC, Australia
| | - Muhammad Mohiuddin
- Cardiac Xenotransplantation Program, University of Maryland School of Medicine, Baltimore, Maryland, USA
| | - David K C Cooper
- Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, USA
| | - Wayne J Hawthorne
- The Department of Surgery, University of Sydney, Westmead Hospital, Westmead, NSW, Australia
- The Centre for Transplant & Renal Research, The Westmead Institute for Medical Research, Westmead, NSW, Australia
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Ames EG, Anand PM, Bekheirnia MR, Doshi MD, El Ters M, Freese ME, Gbadegesin RA, Guay-Woodford LM, Java A, Ranch D, Rodig NM, Wang X, Thomas CP. Evaluation for genetic disease in kidney transplant candidates: A practice resource. Am J Transplant 2025; 25:237-249. [PMID: 39488252 DOI: 10.1016/j.ajt.2024.10.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2024] [Revised: 10/08/2024] [Accepted: 10/24/2024] [Indexed: 11/04/2024]
Abstract
The increasing availability of clinically approved genetic tests for kidney disease has spurred the growth in the use of these tests in kidney transplant practice. Neither the testing options nor the patient population where this should be deployed has been defined, and its value in kidney transplant evaluation has not been demonstrated. Transplant providers may not always be aware of the limitations of genetic testing and may need guidance on comprehending test results and providing counsel, as many centers do not have easy access to a renal genetic counselor or a clinical geneticist. In this practice resource, a working group of nephrologists, geneticists, and a genetic counselor provide a pragmatic, tailored approach to genetic testing, advocating for its use only where the genetic diagnosis or its exclusion can impact the choices available for transplantation or posttransplant management or the workup of living donor candidates at increased risk for heritable disease.
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Affiliation(s)
- Elizabeth G Ames
- Division of Pediatric Genetics, Metabolism, and Genomic Medicine, Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA
| | - Prince M Anand
- Department of Internal Medicine, Medical University of South Carolina, Lancaster, South Carolina, USA
| | - Mir Reza Bekheirnia
- Departments of Molecular and Human Genetics and Pediatrics, Baylor College of Medicine, Houston, Texas, USA; Michael E. Debakey VA Medical Center, Houston, Texas, USA
| | - Mona D Doshi
- Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Mireille El Ters
- Division of Nephrology, Department of Medicine, William von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, Minnesota, USA
| | - Margaret E Freese
- Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
| | - Rasheed A Gbadegesin
- Division of Nephrology, Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA
| | - Lisa M Guay-Woodford
- Divisions of Nephrology and Genetics, Research Institute and Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
| | - Anuja Java
- Division of Nephrology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Daniel Ranch
- Department of Pediatrics, University of Texas Health Science Center, San Antonio, Texas, USA
| | - Nancy M Rodig
- Division of Nephrology, Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts, USA
| | - Xiangling Wang
- Center for Personalized Genetic Healthcare, Department of Kidney Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA
| | - Christie P Thomas
- Division of Nephrology, Department of Medicine, William von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, Minnesota, USA; Department of Internal Medicine, VA Medical Center, Iowa City, Iowa, USA.
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7
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Regalia A, Abinti M, Alfieri CM, Campise M, Verdesca S, Zanoni F, Castellano G. Post-transplant glomerular diseases: update on pathophysiology, risk factors and management strategies. Clin Kidney J 2024; 17:sfae320. [PMID: 39664990 PMCID: PMC11630810 DOI: 10.1093/ckj/sfae320] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2024] [Indexed: 12/13/2024] Open
Abstract
In recent years, advancements in immunosuppressive medications and post-transplant management have led to a significant decrease in acute rejection rates in renal allografts and consequent improvement in short-term graft survival. In contrast, recent data have shown an increased incidence of post-transplant glomerular diseases, which currently represent a leading cause of allograft loss. Although pathogenesis is not fully understood, growing evidence supports the role of inherited and immunological factors and has identified potential pre- and post-transplant predictors. In this review, we illustrate recent advancements in the pathogenesis of post-transplant glomerular disease and the role of risk factors and immunological triggers. In addition, we discuss potential prevention and management strategies.
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Affiliation(s)
- Anna Regalia
- Department of Nephrology, Dialysis and Renal Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Matteo Abinti
- Department of Nephrology, Dialysis and Renal Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy
- Post-Graduate School of Specialization in Nephrology, University of Milan, Milan, Italy
| | - Carlo Maria Alfieri
- Department of Nephrology, Dialysis and Renal Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy
| | - Mariarosaria Campise
- Department of Nephrology, Dialysis and Renal Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Simona Verdesca
- Department of Nephrology, Dialysis and Renal Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Francesca Zanoni
- Department of Nephrology, Dialysis and Renal Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Giuseppe Castellano
- Department of Nephrology, Dialysis and Renal Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy
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8
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Gately R, Wong G, Teixeira-Pinto A, Pilmore H, Hawley C, Campbell S, Mulley W, Lim WH. Access to Waitlisting and Posttransplant Outcomes in Patients With Failed Kidney Allografts Secondary to Recurrent Glomerulonephritis. Transplant Direct 2024; 10:e1717. [PMID: 39440202 PMCID: PMC11495686 DOI: 10.1097/txd.0000000000001717] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2024] [Accepted: 08/15/2024] [Indexed: 10/25/2024] Open
Abstract
Background Recurrent glomerulonephritis (GN) is an important cause of allograft loss after transplantation when GN is the primary cause of kidney failure. Retransplantation after allograft loss from recurrent disease requires careful consideration. We aimed to determine the probability of relisting and the risk of allograft loss after retransplantation in recipients with prior allograft loss from recurrent GN. Methods Using data from the Australia and New Zealand Dialysis and Transplant Registry and multivariable Cox modeling, we compared the probability of waitlisting and allograft loss after second transplantation between those with and without prior allograft loss from recurrent disease. Results Of 3276 patients who received a second kidney transplant, 179 (5%) lost their first allograft from recurrent GN. Between 2006 and 2021, 1524 patients with failed first allografts (6% with recurrent GN, 45% with primary GN but no disease recurrence) were relisted for transplantation. Compared with patients without primary GN, the adjusted hazard ratios (95% confidence intervals) for relisting in patients with primary GN, with and without disease recurrence, were 1.09 (0.88-1.34) and 1.16 (1.05-1.29), respectively. The respective adjusted hazard ratios for allograft loss after repeat transplantation were 0.77 (0.59-1) and 1.02 (0.9-1.16). Of the 81 patients who received a second allograft after losing their first allograft to GN recurrence, 18 patients (22%) also lost their second allograft because of recurrent GN. Conclusions Patients with prior allograft loss from GN recurrence were not disadvantaged, with comparable waitlist potential and allograft outcome after repeat transplantation. However, >20% of those with prior allograft loss from disease recurrence also lost their second allografts from recurrent disease.
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Affiliation(s)
- Ryan Gately
- Department of Kidney and Transplant Services, Princess Alexandra Hospital, Brisbane, QLD, Australia
| | - Germaine Wong
- Sydney School of Public Health, University of Sydney, Sydney, NSW, Australia
- Centre for Kidney Research, Kids Research Institute, The Children’s Hospital at Westmead, Sydney, NSW, Australia
- Department of Renal Medicine, Westmead Hospital, Sydney, NSW, Australia
| | - Armando Teixeira-Pinto
- Sydney School of Public Health, University of Sydney, Sydney, NSW, Australia
- Centre for Kidney Research, Kids Research Institute, The Children’s Hospital at Westmead, Sydney, NSW, Australia
| | - Helen Pilmore
- Department of Renal Medicine, Auckland City Hospital, Auckland, New Zealand
- Department of Medicine, Auckland University, Auckland, New Zealand
| | - Carmel Hawley
- Department of Kidney and Transplant Services, Princess Alexandra Hospital, Brisbane, QLD, Australia
- Australasian Kidney Trials Network, University of Queensland, Brisbane, QLD, Australia
- Translational Research Institute, The University of Queensland, Brisbane, QLD, Australia
| | - Scott Campbell
- Department of Kidney and Transplant Services, Princess Alexandra Hospital, Brisbane, QLD, Australia
| | - William Mulley
- Department of Medicine, Centre for Inflammatory Diseases, Monash University, Clayton, VIC, Australia
- Department of Nephrology, Monash Medical Centre, Clayton, VIC, Australia
| | - Wai H. Lim
- Department of Renal Medicine, Sir Charles Gairdner Hospital, Perth, WA, Australia
- School of Medical and Health Sciences, Edith Cowan University, Perth, WA, Australia
- Medical School, University of Western Australia, Perth, WA, Australia
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Greensmith R, Lape IT, Riella CV, Schubert AJ, Metzger JJ, Dighe AS, Tan X, Hemmer B, Rau J, Wendlinger S, Diederich N, Schütz A, Riella LV, Kaminski MM. CRISPR-enabled point-of-care genotyping for APOL1 genetic risk assessment. EMBO Mol Med 2024; 16:2619-2637. [PMID: 39271961 PMCID: PMC11473833 DOI: 10.1038/s44321-024-00126-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2024] [Revised: 07/19/2024] [Accepted: 08/12/2024] [Indexed: 09/15/2024] Open
Abstract
Detecting genetic variants enables risk factor identification, disease screening, and initiation of preventative therapeutics. However, current methods, relying on hybridization or sequencing, are unsuitable for point-of-care settings. In contrast, CRISPR-based-diagnostics offer high sensitivity and specificity for point-of-care applications. While these methods have predominantly been used for pathogen sensing, their utilization for genotyping is limited. Here, we report a multiplexed CRISPR-based genotyping assay using LwaCas13a, PsmCas13b, and LbaCas12a, enabling the simultaneous detection of six genotypes. We applied this assay to identify genetic variants in the APOL1 gene prevalent among African Americans, which are associated with an 8-30-fold increase in the risk of developing kidney disease. Machine learning facilitated robust analysis across a multicenter clinical cohort of more than 100 patients, accurately identifying their genotypes. In addition, we optimized the readout using a multi-analyte lateral-flow assay demonstrating the ability for simplified genotype determination of clinical samples. Our CRISPR-based genotyping assay enables cost-effective point-of-care genetic variant detection due to its simplicity, versatility, and fast readout.
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Affiliation(s)
- Robert Greensmith
- Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany
- Department of Nephrology and Medical Intensive Care, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Isadora T Lape
- Center for Transplantation Sciences, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA
| | - Cristian V Riella
- Nephrology Division, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, 02215, USA
- Harvard Medical School, Boston, MA, 02115, USA
| | - Alexander J Schubert
- Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany
- Department of Nephrology and Medical Intensive Care, Charité Universitätsmedizin Berlin, Berlin, Germany
- Berlin Institute of Health, Berlin, Germany
| | - Jakob J Metzger
- Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany
| | - Anand S Dighe
- Harvard Medical School, Boston, MA, 02115, USA
- Department of Pathology, Massachusetts General Hospital, Boston, MA, USA
| | - Xiao Tan
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA
- Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA
- Institute for Medical Engineering and Science and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA
- Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | - Bernhard Hemmer
- Department of Neurology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
- Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
| | - Josefine Rau
- Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany
| | - Sarah Wendlinger
- Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany
- Department of Nephrology and Medical Intensive Care, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Nora Diederich
- Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany
- Department of Nephrology and Medical Intensive Care, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Anja Schütz
- Protein Production & Characterization, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, 13125, Berlin, Germany
| | - Leonardo V Riella
- Center for Transplantation Sciences, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
- Department of Surgery, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
- Division of Nephrology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
| | - Michael M Kaminski
- Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
- Department of Nephrology and Medical Intensive Care, Charité Universitätsmedizin Berlin, Berlin, Germany.
- Berlin Institute of Health, Berlin, Germany.
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10
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Pajenda S, Gerges D, Wagner L, O’Connell D, Aiad M, Imre R, Mechtler K, Zimprich A, Schmidt A, Sengoelge G, Winnicki W. Identification of Pathogenic Pathways for Recurrence of Focal Segmental Glomerulosclerosis after Kidney Transplantation. Diagnostics (Basel) 2024; 14:1591. [PMID: 39125467 PMCID: PMC11312181 DOI: 10.3390/diagnostics14151591] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2024] [Revised: 07/11/2024] [Accepted: 07/17/2024] [Indexed: 08/12/2024] Open
Abstract
Primary focal segmental glomerulosclerosis (FSGS) is a disease of the podocytes and glomerulus, leading to nephrotic syndrome and progressive loss of renal function. One of the most serious aspects is its recurrence of disease in over 30% of patients following allogeneic kidney transplantation, leading to early graft loss. This research investigates the individual genetic predispositions and differences in the immune responses leading to recurrence of FSGS after transplantation. We performed exome sequencing on six patients with recurrent FSGS to identify variants in fifty-one genes and found significant variations in the alpha-2-macroglobulin (A2M). Immunoblotting was used to investigate effects of specific gene variants at the protein level. Further expression analysis identified A2M, exophilin 5 (EXPH5) and plectin (PLEC) as specific proteins linked to podocytes, endothelial cells, and the glomerulus. Subsequent protein array screening revealed the presence of non-HLA-specific antibodies, including TRIM21, after transplantation. Using Metascape for pathway and process enrichment analysis, we focused on the IL-17 signaling and chemotaxis pathways. ELISA measurements showed significantly elevated IL-17 levels in patients with recurrent FSGS (32.30 ± 9.12 pg/mL) compared to individuals with other glomerular diseases (23.16 ± 2.49 pg/mL; p < 0.01) and healthy subjects (22.28 ± 0.94 pg/mL; p < 0.01), with no significant difference in plasma CCL2/MCP-1 levels between groups. This study explores the molecular dynamics underlying recurrence of FSGS after transplantation, offering insights into potential biomarkers and therapeutic targets for the future development of individualized treatments for transplant patients.
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Affiliation(s)
- Sahra Pajenda
- Department of Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, 1090 Vienna, Austria; (S.P.); (D.G.); (M.A.); (A.S.); (G.S.); (W.W.)
| | - Daniela Gerges
- Department of Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, 1090 Vienna, Austria; (S.P.); (D.G.); (M.A.); (A.S.); (G.S.); (W.W.)
| | - Ludwig Wagner
- Department of Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, 1090 Vienna, Austria; (S.P.); (D.G.); (M.A.); (A.S.); (G.S.); (W.W.)
| | - David O’Connell
- BiOrbic—Bioeconomy Research Centre, University College Dublin, Belfield, D04 V1W8 Dublin, Ireland;
- School of Biomolecular and Biomedical Science, University College Dublin, Belfield, D04 V1W8 Dublin, Ireland
| | - Monika Aiad
- Department of Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, 1090 Vienna, Austria; (S.P.); (D.G.); (M.A.); (A.S.); (G.S.); (W.W.)
| | - Richard Imre
- ProtChem Facility, IMP-IMBA, Research Institute of Molecular Pathology—Institute of Molecular Biotechnology, 1030 Vienna, Austria; (R.I.); (K.M.)
| | - Karl Mechtler
- ProtChem Facility, IMP-IMBA, Research Institute of Molecular Pathology—Institute of Molecular Biotechnology, 1030 Vienna, Austria; (R.I.); (K.M.)
| | - Alexander Zimprich
- Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria;
| | - Alice Schmidt
- Department of Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, 1090 Vienna, Austria; (S.P.); (D.G.); (M.A.); (A.S.); (G.S.); (W.W.)
| | - Guerkan Sengoelge
- Department of Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, 1090 Vienna, Austria; (S.P.); (D.G.); (M.A.); (A.S.); (G.S.); (W.W.)
| | - Wolfgang Winnicki
- Department of Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, 1090 Vienna, Austria; (S.P.); (D.G.); (M.A.); (A.S.); (G.S.); (W.W.)
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11
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Bartoli G, Dello Strologo A, Grandaliano G, Pesce F. Updates on C3 Glomerulopathy in Kidney Transplantation: Pathogenesis and Treatment Options. Int J Mol Sci 2024; 25:6508. [PMID: 38928213 PMCID: PMC11204074 DOI: 10.3390/ijms25126508] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Revised: 06/01/2024] [Accepted: 06/08/2024] [Indexed: 06/28/2024] Open
Abstract
C3 glomerulopathy is a rare disease, characterized by an abnormal activation of the complement's alternative pathway that leads to the accumulation of the C3 component in the kidney. The disease recurs in more than half of kidney transplant recipients, with a significant impact on graft survival. Recurrence of the primary disease represents the second cause of graft loss after organ rejection. In C3 glomerulopathy, there are several risk factors which can promote a recurrence during transplantation, such as delayed graft function, infection and monoclonal gammopathy. All these events can trigger the alternative complement pathway. In this review, we summarize the impact of C3 glomerulopathy on kidney grafts and present the latest treatment options. The most widely used treatments for the disease include corticosteroids and mycophenolate mofetil, which are already used chronically by kidney transplant recipients; thus, additional treatments for C3 glomerulopathy are required. Currently, several studies using anti-complement drugs (i.e., eculizumab, Ravalizumab, avacopan) for C3 glomerulopathy in kidney transplant patients are ongoing with encouraging results.
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Affiliation(s)
- Giulia Bartoli
- Department of Translational Medicine and Surgery, Università Cattolica dl Sacro Cuore, 00168 Rome, Italy; (G.B.); (A.D.S.); (G.G.)
| | - Andrea Dello Strologo
- Department of Translational Medicine and Surgery, Università Cattolica dl Sacro Cuore, 00168 Rome, Italy; (G.B.); (A.D.S.); (G.G.)
| | - Giuseppe Grandaliano
- Department of Translational Medicine and Surgery, Università Cattolica dl Sacro Cuore, 00168 Rome, Italy; (G.B.); (A.D.S.); (G.G.)
- Nephrology, Dialysis and Transplantation Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Francesco Pesce
- Department of Translational Medicine and Surgery, Università Cattolica dl Sacro Cuore, 00168 Rome, Italy; (G.B.); (A.D.S.); (G.G.)
- Division of Renal Medicine, “Ospedale Isola Tiberina—Gemelli Isola”, 00186 Rome, Italy
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12
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Hullekes F, Uffing A, Verhoeff R, Seeger H, von Moos S, Mansur J, Mastroianni-Kirsztajn G, Silva HT, Buxeda A, Pérez-Sáez MJ, Arias-Cabrales C, Collins AB, Swett C, Morená L, Loucaidou M, Kousios A, Malvezzi P, Bugnazet M, Russo LS, Muhsin SA, Agrawal N, Nissaisorakarn P, Patel H, Al Jurdi A, Akalin E, Neto ED, Agena F, Ventura C, Manfro RC, Bauer AC, Mazzali M, de Sousa MV, La Manna G, Bini C, Comai G, Reindl-Schwaighofer R, Berger S, Cravedi P, Riella LV. Recurrence of membranous nephropathy after kidney transplantation: A multicenter retrospective cohort study. Am J Transplant 2024; 24:1016-1026. [PMID: 38341027 DOI: 10.1016/j.ajt.2024.01.036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Revised: 01/30/2024] [Accepted: 01/31/2024] [Indexed: 02/12/2024]
Abstract
Membranous nephropathy (MN) is a leading cause of kidney failure worldwide and frequently recurs after transplant. Available data originated from small retrospective cohort studies or registry analyses; therefore, uncertainties remain on risk factors for MN recurrence and response to therapy. Within the Post-Transplant Glomerular Disease Consortium, we conducted a retrospective multicenter cohort study examining the MN recurrence rate, risk factors, and response to treatment. This study screened 22,921 patients across 3 continents and included 194 patients who underwent a kidney transplant due to biopsy-proven MN. The cumulative incidence of MN recurrence was 31% at 10 years posttransplant. Patients with a faster progression toward end-stage kidney disease were at higher risk of developing recurrent MN (hazard ratio [HR], 0.55 per decade; 95% confidence interval [CI], 0.35-0.88). Moreover, elevated pretransplant levels of anti-phospholipase A2 receptor (PLA2R) antibodies were strongly associated with recurrence (HR, 18.58; 95% CI, 5.37-64.27). Patients receiving rituximab for MN recurrence had a higher likelihood of achieving remission than patients receiving renin-angiotensin-aldosterone system inhibition alone. In sum, MN recurs in one-third of patients posttransplant, and measurement of serum anti-PLA2R antibody levels shortly before transplant could aid in risk-stratifying patients for MN recurrence. Moreover, patients receiving rituximab had a higher rate of treatment response.
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Affiliation(s)
- Frank Hullekes
- Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA; Groningen Transplant Center, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Audrey Uffing
- Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA; Groningen Transplant Center, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Rucháma Verhoeff
- Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA; Department of Surgery, Erasmus Medical Center Transplant Institute, Erasmus University, Rotterdam, The Netherlands
| | - Harald Seeger
- Division of Nephrology, University Hospital Zurich, Zurich, Switzerland
| | - Seraina von Moos
- Division of Nephrology, University Hospital Zurich, Zurich, Switzerland
| | - Juliana Mansur
- Division of Nephrology, Federal University of Sao Paulo, Sao Paulo, Brazil
| | | | | | - Anna Buxeda
- Division of Nephrology, Hospital del Mar, Barcelona, Spain
| | | | | | - A Bernard Collins
- Renal Pathology, Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Christie Swett
- Renal Pathology, Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Leela Morená
- Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | | | | | - Paolo Malvezzi
- Department of Nephrology, Dialysis, Apheresis and Transplantation, CHU Grenoble Alpes, Grenoble, France
| | - Mathilde Bugnazet
- Department of Nephrology, Dialysis, Apheresis and Transplantation, CHU Grenoble Alpes, Grenoble, France
| | - Luis Sanchez Russo
- Translational Transplant Research Center, Renal Division, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Saif A Muhsin
- Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Nikhil Agrawal
- Division of Nephrology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Pitchaphon Nissaisorakarn
- Division of Nephrology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Het Patel
- Division of Nephrology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Ayman Al Jurdi
- Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA; Department of Medicine, Nephrology Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Enver Akalin
- Einstein/Montefiore Transplant Center, Albert Einstein College of Medicine, Bronx, New York, USA
| | - Elias David Neto
- Renal Transplant Service, Division of Nephrology, University of Sao Paulo School of Medicine, Sao Paulo, Brazil
| | - Fabiana Agena
- Renal Transplant Service, Division of Nephrology, University of Sao Paulo School of Medicine, Sao Paulo, Brazil
| | - Carlucci Ventura
- Renal Transplant Service, Division of Nephrology, University of Sao Paulo School of Medicine, Sao Paulo, Brazil
| | - Roberto C Manfro
- Division of Nephrology, Hospital de clínicas de Porto Alegre/Federal University of Rio Grande do Sul, Porto Alegre, Brazil
| | - Andrea Carla Bauer
- Division of Nephrology, Hospital de clínicas de Porto Alegre/Federal University of Rio Grande do Sul, Porto Alegre, Brazil
| | - Marilda Mazzali
- Division of Nephrology, School of Medical Sciences, University of Campinas, Campinas, Brazil
| | | | - Gaetano La Manna
- Nephrology, Dialysis and Renal Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna, Bologna, Italy
| | - Claudia Bini
- Nephrology, Dialysis and Renal Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna, Bologna, Italy
| | - Giorgia Comai
- Nephrology, Dialysis and Renal Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | | | - Stefan Berger
- Groningen Transplant Center, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Paolo Cravedi
- Translational Transplant Research Center, Renal Division, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Leonardo V Riella
- Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA; Department of Medicine, Nephrology Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
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13
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Mansur J, Chang-Dávila D, Simões MG, Cristelli MP, Stopa Martins SB, de Sousa Proença HM, Viana LA, Ferreira AN, Doher MP, Medina-Pestana J, Mastroianni Kirsztajn G, Tedesco-Silva H. Multiple-target Therapy for Posttransplant Focal Segmental Glomerulosclerosis. Transplant Direct 2024; 10:e1651. [PMID: 38817628 PMCID: PMC11139459 DOI: 10.1097/txd.0000000000001651] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Accepted: 03/13/2024] [Indexed: 06/01/2024] Open
Abstract
Background There is no consensus on the ideal strategy to treat posttransplant focal segmental glomerulosclerosis. The multiple-target therapy, which consisted of high-dose intravenous cyclosporine, prednisone, and plasmapheresis, showed favorable results. Methods This single-center, prospective study sought to evaluate the multiple-target therapy in an independent cohort of patients. Results Thirteen patients with posttransplant focal segmental glomerulosclerosis received multiple-target therapy. Complete remission was achieved in 2 patients (15.4%), and partial remission in another 2 patients (15.4%). Four patients (30.7%) did not show remission, and 5 patients (38%) lost the graft because of posttransplant focal segmental glomerulosclerosis during the 12-mo follow-up. Premature discontinuation of treatment occurred in 10 patients (77%), all associated with infectious adverse events. Cytomegalovirus was the most common complication, and preemptive therapy was used instead of prophylaxis. Conclusions In this cohort of patients, the efficacy of the multiple-target therapy was poor and limited by the high incidence of infectious adverse events.
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Affiliation(s)
- Juliana Mansur
- Nephrology Division, Hospital do Rim, Fundação Oswaldo Ramos, São Paulo, Brazil
- Nephrology Division, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil
| | | | - Marcela Giraldes Simões
- Nephrology Division, Hospital do Rim, Fundação Oswaldo Ramos, São Paulo, Brazil
- Nephrology Division, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil
| | | | | | | | - Laila Almeida Viana
- Nephrology Division, Hospital do Rim, Fundação Oswaldo Ramos, São Paulo, Brazil
| | | | | | - José Medina-Pestana
- Nephrology Division, Hospital do Rim, Fundação Oswaldo Ramos, São Paulo, Brazil
- Nephrology Division, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil
| | | | - Helio Tedesco-Silva
- Nephrology Division, Hospital do Rim, Fundação Oswaldo Ramos, São Paulo, Brazil
- Nephrology Division, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil
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14
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Robles NR, García-López V, García-Martínez V. Editorial for "Significance of Arterial Spin Labeling for Reducing Biopsies in Patients With Kidney Allograft Dysfunction". J Magn Reson Imaging 2024; 59:1785-1786. [PMID: 37539813 DOI: 10.1002/jmri.28930] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Accepted: 07/18/2023] [Indexed: 08/05/2023] Open
Affiliation(s)
- Nicolás R Robles
- Service of Nephrology, Badajoz University Hospital, University of Extremadura, Badajoz, Spain
| | - Virginio García-López
- Department of Medical and Surgical Therapeutics, Pharmacology Area, Faculty of Medicine and Health Sciences, University of Extremadura, Badajoz, Spain
| | - Virginio García-Martínez
- Department of Human Anatomy and Embryology, Institute of Molecular Pathology Biomarkers, Faculty of Medicine and Health Sciences, University of Extremadura, Badajoz, Spain
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15
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Nissaisorakarn P, Fadakar PK, Safa K, Lundquist AL, Riella CV, Riella LV. A pragmatic approach to selective genetic testing in kidney transplant candidates. FRONTIERS IN TRANSPLANTATION 2024; 2:1342471. [PMID: 38993907 PMCID: PMC11235289 DOI: 10.3389/frtra.2023.1342471] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Accepted: 12/22/2023] [Indexed: 07/13/2024]
Abstract
Introduction Advances in the field of genetic testing have spurred its use in transplantation. Potential benefits of genetic testing in transplant nephrology include diagnosis, treatment, risk stratification of recurrent disease, and risk stratification in potential donors. However, it is unclear how to best apply genetic testing in this population to maximize its yield. We describe our transplant center's approach to selective genetic testing as part of kidney transplant candidate and donor evaluation. Methods Transplant recipient candidates were tested if they had a history of ESRD at age <50, primary FSGS, complement-mediated or unknown etiology of kidney disease, or had a family history of kidney disease. Donors were tested if age <35, were related to their potential recipients with known genetic susceptibility or had a first-degree relative with a history of kidney disease of unknown etiology. A targeted NGS gene panel of 385 genes was used. Clinical implications and downstream effects were monitored. Results Over 30% of recipients tested within the established criteria were positive for a pathogenic variant. The most common pathogenic variants were APOL1 high-risk genotypes as well as collagen 4-alpha-3, -4 and -5. Donor testing done according to our inclusion criteria resulted in about 12% yield. Positive test results in recipients helped with stratification of the risk of recurrent disease. Positive test results in potential donors guided informed decisions on when not to move forward with a donation. Discussion Integrating targeted panel genetic testing into a kidney transplant clinic in conjunction with a selective criteria for testing donors and recipients ensured a reasonable diagnostic yield. The results had implications on clinical management, risk stratification and in some cases were instrumental in directing downstream changes including when to stop the evaluation process. Given the impact on management and transplant decisions, we advocate for the widespread use of genetic testing in selected individuals undergoing transplant evaluation and donation who meet pre-defined criteria.
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Affiliation(s)
- Pitchaphon Nissaisorakarn
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
| | - Paul K. Fadakar
- Division of Nephrology, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
| | - Kassem Safa
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
| | - Andrew L. Lundquist
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
| | - Cristian V. Riella
- Division of Nephrology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
| | - Leonardo V. Riella
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
- Center for Transplantation Sciences, Department of Surgery Massachusetts General Hospital, Boston, MA, United States
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16
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Ahmad SB, Peleg Y, Ahn W. Current approaches to overcome recurrent focal segmental glomerulosclerosis after kidney transplantation. Curr Opin Nephrol Hypertens 2024; 33:61-66. [PMID: 37921337 DOI: 10.1097/mnh.0000000000000946] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2023]
Abstract
PURPOSE OF REVIEW Recurrent focal segmental glomerulosclerosis (FSGS) presents with nephrotic syndrome shortly after kidney transplantation. This review will overview the role of circulating permeability factors in disease pathogenesis and treatment options for recurrent FSGS. RECENT FINDINGS Novel circulating permeability factors have been identified in serum samples. Current research is focused on detection of permeability factors as a marker of treatment response. Furthermore, novel monoclonal antibodies are being utilized to further induce remission. SUMMARY Posttransplant recurrent FSGS can have a deleterious effect on allograft. Early detection of disease recurrence with prompt treatment is optimal for clinical remission. Plasmapheresis with anti-B cell therapy is considered the mainstay of treatment. Newer B cell therapies and detection of circulating factors in serum may help in providing targeted treatment in a subset of patients.
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Affiliation(s)
- Syeda Behjat Ahmad
- University of Pittsburgh School of Medicine, Division of Renal-Electrolyte, Pittsburgh, Pennsylvania
| | - Yonatan Peleg
- Northwestern University Feinberg School of Medicine, Division of Nephrology and Hypertension, Chicago, Illinois
| | - Wooin Ahn
- Oregon Health & Science University School of Medicine, Division of Nephrology and Hypertension, Portland, Oregon, USA
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17
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Stamellou E, Seikrit C, Tang SCW, Boor P, Tesař V, Floege J, Barratt J, Kramann R. IgA nephropathy. Nat Rev Dis Primers 2023; 9:67. [PMID: 38036542 DOI: 10.1038/s41572-023-00476-9] [Citation(s) in RCA: 66] [Impact Index Per Article: 33.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/26/2023] [Indexed: 12/02/2023]
Abstract
IgA nephropathy (IgAN), the most prevalent primary glomerulonephritis worldwide, carries a considerable lifetime risk of kidney failure. Clinical manifestations of IgAN vary from asymptomatic with microscopic or intermittent macroscopic haematuria and stable kidney function to rapidly progressive glomerulonephritis. IgAN has been proposed to develop through a 'four-hit' process, commencing with overproduction and increased systemic presence of poorly O-glycosylated galactose-deficient IgA1 (Gd-IgA1), followed by recognition of Gd-IgA1 by antiglycan autoantibodies, aggregation of Gd-IgA1 and formation of polymeric IgA1 immune complexes and, lastly, deposition of these immune complexes in the glomerular mesangium, leading to kidney inflammation and scarring. IgAN can only be diagnosed by kidney biopsy. Extensive, optimized supportive care is the mainstay of therapy for patients with IgAN. For those at high risk of disease progression, the 2021 KDIGO Clinical Practice Guideline suggests considering a 6-month course of systemic corticosteroid therapy; however, the efficacy of systemic steroid treatment is under debate and serious adverse effects are common. Advances in understanding the pathophysiology of IgAN have led to clinical trials of novel targeted therapies with acceptable safety profiles, including SGLT2 inhibitors, endothelin receptor blockers, targeted-release budesonide, B cell proliferation and differentiation inhibitors, as well as blockade of complement components.
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Affiliation(s)
- Eleni Stamellou
- Department of Nephrology, School of Medicine, University of Ioannina, Ioannina, Greece
- Department of Nephrology and Clinical Immunology, RWTH Aachen University Hospital, Aachen, Germany
| | - Claudia Seikrit
- Department of Nephrology and Clinical Immunology, RWTH Aachen University Hospital, Aachen, Germany
| | - Sydney C W Tang
- Division of Nephrology, Department of Medicine, University of Hong Kong, Hong Kong, China
| | - Peter Boor
- Department of Nephrology and Clinical Immunology, RWTH Aachen University Hospital, Aachen, Germany
- Department of Pathology, RWTH Aachen University, Aachen, Germany
| | - Vladimir Tesař
- Department of Nephrology, 1st Faculty of Medicine and General University Hospital, Charles University, Prague, Czech Republic
| | - Jürgen Floege
- Department of Nephrology and Clinical Immunology, RWTH Aachen University Hospital, Aachen, Germany
| | - Jonathan Barratt
- Department of Cardiovascular Sciences, University of Leicester, Leicester, UK
| | - Rafael Kramann
- Department of Nephrology and Clinical Immunology, RWTH Aachen University Hospital, Aachen, Germany.
- Department of Internal Medicine, Nephrology and Transplantation, Erasmus Medical Center, Rotterdam, Netherlands.
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18
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Peritore L, Labbozzetta V, Maressa V, Casuscelli C, Conti G, Gembillo G, Santoro D. How to Choose the Right Treatment for Membranous Nephropathy. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1997. [PMID: 38004046 PMCID: PMC10673286 DOI: 10.3390/medicina59111997] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Revised: 10/30/2023] [Accepted: 11/12/2023] [Indexed: 11/26/2023]
Abstract
Membranous nephropathy is an autoimmune disease affecting the glomeruli and is one of the most common causes of nephrotic syndrome. In the absence of any therapy, 35% of patients develop end-stage renal disease. The discovery of autoantibodies such as phospholipase A2 receptor 1, antithrombospondin and neural epidermal growth factor-like 1 protein has greatly helped us to understand the pathogenesis and enable the diagnosis of this disease and to guide its treatment. Depending on the complications of nephrotic syndrome, patients with this disease receive supportive treatment with diuretics, ACE inhibitors or angiotensin-receptor blockers, lipid-lowering agents and anticoagulants. After assessing the risk of progression of end-stage renal disease, patients receive immunosuppressive therapy with various drugs such as cyclophosphamide, steroids, calcineurin inhibitors or rituximab. Since immunosuppressive drugs can cause life-threatening side effects and up to 30% of patients do not respond to therapy, new therapeutic approaches with drugs such as adrenocorticotropic hormone, belimumab, anti-plasma cell antibodies or complement-guided drugs are currently being tested. However, special attention needs to be paid to the choice of therapy in secondary forms or in specific clinical contexts such as membranous disease in children, pregnant women and patients undergoing kidney transplantation.
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Affiliation(s)
- Luigi Peritore
- Unit of Nephrology and Dialysis, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy; (V.L.); (V.M.); (C.C.)
| | - Vincenzo Labbozzetta
- Unit of Nephrology and Dialysis, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy; (V.L.); (V.M.); (C.C.)
| | - Veronica Maressa
- Unit of Nephrology and Dialysis, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy; (V.L.); (V.M.); (C.C.)
| | - Chiara Casuscelli
- Unit of Nephrology and Dialysis, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy; (V.L.); (V.M.); (C.C.)
| | - Giovanni Conti
- Pediatric Nephrology Unit, AOU Policlinic “G Martino”, University of Messina, 98125 Messina, Italy;
| | - Guido Gembillo
- Unit of Nephrology and Dialysis, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy; (V.L.); (V.M.); (C.C.)
| | - Domenico Santoro
- Unit of Nephrology and Dialysis, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy; (V.L.); (V.M.); (C.C.)
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19
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Esposito P, Picciotto D, Cappadona F, Costigliolo F, Russo E, Macciò L, Viazzi F. Multifaceted relationship between diabetes and kidney diseases: Beyond diabetes. World J Diabetes 2023; 14:1450-1462. [PMID: 37970131 PMCID: PMC10642421 DOI: 10.4239/wjd.v14.i10.1450] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 08/18/2023] [Accepted: 08/28/2023] [Indexed: 10/09/2023] Open
Abstract
Diabetes mellitus is one of the most common causes of chronic kidney disease. Kidney involvement in patients with diabetes has a wide spectrum of clinical presentations ranging from asymptomatic to overt proteinuria and kidney failure. The development of kidney disease in diabetes is associated with structural changes in multiple kidney compartments, such as the vascular system and glomeruli. Glomerular alterations include thickening of the glomerular basement membrane, loss of podocytes, and segmental mesangiolysis, which may lead to microaneurysms and the development of pathognomonic Kimmelstiel-Wilson nodules. Beyond lesions directly related to diabetes, awareness of the possible coexistence of nondiabetic kidney disease in patients with diabetes is increasing. These nondiabetic lesions include focal segmental glomerulosclerosis, IgA nephropathy, and other primary or secondary renal disorders. Differential diagnosis of these conditions is crucial in guiding clinical management and therapeutic approaches. However, the relationship between diabetes and the kidney is bidirectional; thus, new-onset diabetes may also occur as a complication of the treatment in patients with renal diseases. Here, we review the complex and multifaceted correlation between diabetes and kidney diseases and discuss clinical presentation and course, differential diagnosis, and therapeutic oppor-tunities offered by novel drugs.
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Affiliation(s)
- Pasquale Esposito
- Department of Internal Medicine and Medical Specialties (DiMI), University of Genoa, Genoa 16132, Italy
- Unit of Nephrology, Dialysis and Transplantation, IRCCS Ospedale Policlinico San Martino, Genoa 16132, Italy
| | - Daniela Picciotto
- Unit of Nephrology, Dialysis and Transplantation, IRCCS Ospedale Policlinico San Martino, Genoa 16132, Italy
| | - Francesca Cappadona
- Unit of Nephrology, Dialysis and Transplantation, IRCCS Ospedale Policlinico San Martino, Genoa 16132, Italy
| | - Francesca Costigliolo
- Unit of Nephrology, Dialysis and Transplantation, IRCCS Ospedale Policlinico San Martino, Genoa 16132, Italy
| | - Elisa Russo
- Department of Internal Medicine and Medical Specialties (DiMI), University of Genoa, Genoa 16132, Italy
- Unit of Nephrology, Dialysis and Transplantation, IRCCS Ospedale Policlinico San Martino, Genoa 16132, Italy
| | - Lucia Macciò
- Department of Internal Medicine and Medical Specialties (DiMI), University of Genoa, Genoa 16132, Italy
| | - Francesca Viazzi
- Department of Internal Medicine and Medical Specialties (DiMI), University of Genoa, Genoa 16132, Italy
- Unit of Nephrology, Dialysis and Transplantation, IRCCS Ospedale Policlinico San Martino, Genoa 16132, Italy
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20
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Schnuelle P. Renal Biopsy for Diagnosis in Kidney Disease: Indication, Technique, and Safety. J Clin Med 2023; 12:6424. [PMID: 37835066 PMCID: PMC10573674 DOI: 10.3390/jcm12196424] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Revised: 09/29/2023] [Accepted: 10/04/2023] [Indexed: 10/15/2023] Open
Abstract
Renal biopsies are the gold standard for diagnosis, staging, and prognosis of underlying parenchymal kidney disease. This article provides an overview of the current indications and highlights ways to reduce bleeding complications in order to achieve optimal diagnostic yield with minimal risk to the patient. Novel indications have emerged from the increasing use of new molecularly targeted oncologic therapies in recent years, which often induce immune-mediated renal disease. On the other hand, the detection of specific antibodies against target antigens on podocytes in the sera of patients with new-onset nephrotic syndrome has now relativized the indication for biopsy in membranous nephropathy. The use of semi-automatic spring-loaded biopsy devices and real-time ultrasound considerably declined the complication rate and is the current standard. Percutaneous renal biopsies are overall a safe procedure if contraindications are considered. A coagulation disorder needs to be excluded beforehand, and an elevated blood pressure must be reduced to the normotensive range with medications. A laparoscopic approach or a radiology interventional procedure through the internal jugular vein may be considered for obtaining a kidney tissue sample if there is an urgent indication and a bleeding tendency cannot be adequately corrected. Major bleeding after a percutaneous renal biopsy can usually be managed with selective arterial embolization of the injured renal vessel. The use of a 16-gauge needle is the most reasonable compromise between diagnostic benefit and risk of complication. In the routine diagnostic, the biopsy specimen is examined with light microscopy, immunohistochemistry, and electron microscopy. Combination with modern molecular pathology techniques will contribute to more precise insights into the development and progression of kidney disease, which will likely refine future treatments in nephrology.
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Affiliation(s)
- Peter Schnuelle
- Center for Renal Diseases Weinheim, Academic Teaching Practice of the University Medical Center Mannheim, University of Heidelberg, D-69469 Weinheim, Germany
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21
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Knight SR. Transplant Trial Watch. Transpl Int 2023; 36:11816. [PMID: 37621983 PMCID: PMC10444948 DOI: 10.3389/ti.2023.11816] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Accepted: 07/26/2023] [Indexed: 08/26/2023]
Affiliation(s)
- Simon R. Knight
- Oxford Transplant Centre, Churchill Hospital, Oxford, United Kingdom
- Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom
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22
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Lim JH, Shin SW, Kim MS, Han MH, Kim YJ, Jung HY, Choi JY, Cho JH, Park SH, Kim YL, Hwang D, Yun WS, Kim HK, Huh S, Yoo ES, Won DI, Kim CD. Recurrent C3 Glomerulonephritis along with BK-Virus-Associated Nephropathy after Kidney Transplantation: A Case Report. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1308. [PMID: 37512118 PMCID: PMC10383463 DOI: 10.3390/medicina59071308] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Revised: 07/12/2023] [Accepted: 07/13/2023] [Indexed: 07/30/2023]
Abstract
C3 glomerulonephritis (C3GN) is a rare cause of end-stage kidney disease and frequently recurrent in allografts following kidney transplantation (KT). Herein, we describe the case of a kidney transplant recipient who developed recurrent C3GN along with BK-virus-associated nephropathy (BKVAN) following KT. A 33-year-old man diagnosed with membranoproliferative glomerulonephritis 17 years ago underwent preemptive KT with a donor kidney from his aunt. Proteinuria gradually increased after 3 months following KT, and graft biopsy was performed 30 months after KT. Histopathological examination revealed recurrent C3GN. The dosages of triple immunosuppressive maintenance therapy agents were increased. Subsequently, serum C3 levels recovered to normal levels. However, at 33 months following KT, the BK viral load increased and graft function gradually deteriorated; a second graft biopsy was performed at 46 months following KT, which revealed BKVAN and decreased C3GN activity. The dosages of immunosuppressive agents were decreased; subsequently, BKVAN improved and graft function was maintained with normal serum C3 levels at 49 months following KT. This case indicates that C3GN is highly prone to recurrence following KT and that immunosuppressive therapy for C3GN increases the risk of BKVAN.
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Affiliation(s)
- Jeong-Hoon Lim
- Department of Internal Medicine, School of Medicine, Kyungpook National University Hospital, Kyungpook National University, Daegu 41944, Republic of Korea
| | - Seong-Won Shin
- Department of Internal Medicine, School of Medicine, Kyungpook National University Hospital, Kyungpook National University, Daegu 41944, Republic of Korea
| | - Mee-Seon Kim
- Department of Pathology, School of Medicine, Kyungpook National University Hospital, Kyungpook National University, Daegu 41944, Republic of Korea
| | - Man-Hoon Han
- Department of Pathology, School of Medicine, Kyungpook National University Hospital, Kyungpook National University, Daegu 41944, Republic of Korea
| | - Yong-Jin Kim
- Department of Pathology, School of Medicine, Kyungpook National University Hospital, Kyungpook National University, Daegu 41944, Republic of Korea
| | - Hee-Yeon Jung
- Department of Internal Medicine, School of Medicine, Kyungpook National University Hospital, Kyungpook National University, Daegu 41944, Republic of Korea
| | - Ji-Young Choi
- Department of Internal Medicine, School of Medicine, Kyungpook National University Hospital, Kyungpook National University, Daegu 41944, Republic of Korea
| | - Jang-Hee Cho
- Department of Internal Medicine, School of Medicine, Kyungpook National University Hospital, Kyungpook National University, Daegu 41944, Republic of Korea
| | - Sun-Hee Park
- Department of Internal Medicine, School of Medicine, Kyungpook National University Hospital, Kyungpook National University, Daegu 41944, Republic of Korea
| | - Yong-Lim Kim
- Department of Internal Medicine, School of Medicine, Kyungpook National University Hospital, Kyungpook National University, Daegu 41944, Republic of Korea
| | - Deokbi Hwang
- Department of Surgery, School of Medicine, Kyungpook National University Hospital, Kyungpook National University, Daegu 41944, Republic of Korea
| | - Woo-Sung Yun
- Department of Surgery, School of Medicine, Kyungpook National University Hospital, Kyungpook National University, Daegu 41944, Republic of Korea
| | - Hyung-Kee Kim
- Department of Surgery, School of Medicine, Kyungpook National University Hospital, Kyungpook National University, Daegu 41944, Republic of Korea
| | - Seung Huh
- Department of Surgery, School of Medicine, Kyungpook National University Hospital, Kyungpook National University, Daegu 41944, Republic of Korea
| | - Eun Sang Yoo
- Department of Urology, School of Medicine, Kyungpook National University Hospital, Kyungpook National University, Daegu 41944, Republic of Korea
| | - Dong Il Won
- Department of Clinical Pathology, School of Medicine, Kyungpook National University Hospital, Kyungpook National University, Daegu 41944, Republic of Korea
| | - Chan-Duck Kim
- Department of Internal Medicine, School of Medicine, Kyungpook National University Hospital, Kyungpook National University, Daegu 41944, Republic of Korea
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23
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Masutani K. Progress in Pathological Diagnosis after Kidney Transplantation: Current Trend and Future Perspective. J Atheroscler Thromb 2023; 30:720-732. [PMID: 37245995 PMCID: PMC10322740 DOI: 10.5551/jat.rv22005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Accepted: 05/16/2023] [Indexed: 05/30/2023] Open
Abstract
Advances in immunosuppressive therapy; posttransplant management of allograft rejection; and measures against infectious diseases, cardiovascular diseases, and malignancy dramatically improved graft and patient survival after kidney transplantation (KT). Among them, kidney allograft biopsy is an important tool and the gold standard for the diagnosis of various kidney allograft injuries, including allograft rejection, virus-induced nephropathy, calcineurin inhibitor toxicity, and posttransplant glomerular diseases. The Banff Conference on Allograft Pathology has contributed to establishing the diagnostic criteria for kidney allograft rejection and polyomavirus-associated nephropathy that are used as a common standard worldwide. In addition to the for-cause biopsy, many transplant centers perform protocol biopsies in the early and late posttransplant periods to detect and treat allograft injury earlier. Preimplantation biopsy in deceased-donor KT has also been performed, especially in the marginal donor, and attempts have been made to predict the prognosis in combination with clinical information and the renal resistance of hypothermic machine perfusion. Regarding the preimplantation biopsy from a living kidney donor, it can provide useful information on aging and/or early changes in lifestyle diseases, such as glomerulosclerosis, tubulointerstitial changes, and arterial and arteriolar sclerosis, and be used as a reference for the subsequent management of living donors. In this review, morphologic features of important kidney allograft pathology, such as allograft rejection and polyomavirus-associated nephropathy, according to the latest Banff classification and additional information derived from protocol biopsy, and future perspectives with recently developed technologies are discussed.
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Affiliation(s)
- Kosuke Masutani
- Division of Nephrology and Rheumatology, Department of Internal Medicine, Faculty of Medicine, Fukuoka University, Fukuoka,
Japan
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24
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Acharya R, Upadhyay K. Early recurrence of focal segmental glomerulosclerosis in a kidney transplant recipient with APOL1 one risk variant. BMJ Case Rep 2023; 16:e254593. [PMID: 37258049 PMCID: PMC10254708 DOI: 10.1136/bcr-2023-254593] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/18/2023] [Indexed: 06/02/2023] Open
Abstract
Apolipoprotein 1 (APOL1) risk variants (G1 and G2) are associated with focal segmental glomerulosclerosis (FSGS) in patients of African ancestry. The prevalence of APOL1 two risk variants is lower in Hispanics and very rare in European and Asian populations. APOL1 two risk variants in donor kidneys is associated with recipient kidney graft loss, however the effect of recipient risk variant in the kidney transplant outcome is unclear. Here, we present a late adolescent male with FSGS and end stage renal disease with one APOL1 risk variant (G2) who had immediate recurrence of FSGS in the post-KT period. There was an excellent response to few sessions of plasmapheresis and Rituximab with no further recurrence of FSGS in the 1 year follow-up period. It needs to be seen whether the recipient APOL1 single risk variant causes increased susceptibility to kidney graft loss on a long run via recurrent or de novo pathologies.
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Affiliation(s)
- Ratna Acharya
- Paediatrics, University of Florida, Gainesville, Florida, USA
| | - Kiran Upadhyay
- Paediatrics and Nephrology, University of Florida Health, Gainesville, Florida, USA
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25
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Dantas M, Silva LBB, Pontes BTM, dos Reis MA, de Lima PSN, Moysés M. Membranous nephropathy. J Bras Nefrol 2023; 45:229-243. [PMID: 37527529 PMCID: PMC10627124 DOI: 10.1590/2175-8239-jbn-2023-0046en] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Accepted: 05/31/2023] [Indexed: 08/03/2023] Open
Abstract
Membranous nephropathy is a glomerulopathy, which main affected target is the podocyte, and has consequences on the glomerular basement membrane. It is more common in adults, especially over 50 years of age. The clinical presentation is nephrotic syndrome, but many cases can evolve with asymptomatic non-nephrotic proteinuria. The mechanism consists of the deposition of immune complexes in the subepithelial space of the glomerular capillary loop with subsequent activation of the complement system. Great advances in the identification of potential target antigens have occurred in the last twenty years, and the main one is the protein "M-type phospholipase-A2 receptor" (PLA2R) with the circulating anti-PLA2R antibody, which makes it possible to evaluate the activity and prognosis of this nephropathy. This route of injury corresponds to approximately 70% to 80% of cases of membranous nephropathy characterized as primary. In the last 10 years, several other potential target antigens have been identified. This review proposes to present clinical, etiopathogenic and therapeutic aspects of membranous nephropathy in a didactic manner, including cases that occur during kidney transplantation.
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Affiliation(s)
- Márcio Dantas
- Universidade de São Paulo, Faculdade de Medicina, Hospital das
Clínicas, Ribeirão Preto, SP, Brazil
| | | | | | - Marlene Antônia dos Reis
- Universidade Federal do Triângulo Mineiro, Patologia Geral, Centro
de Pesquisa em Rim, Uberaba, MG, Brazil
| | | | - Miguel Moysés
- Universidade de São Paulo, Faculdade de Medicina, Hospital das
Clínicas, Ribeirão Preto, SP, Brazil
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26
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Atlas-Lazar A, Levy-Erez D. Approach to acute kidney injury following paediatric kidney transplant. Curr Opin Pediatr 2023; 35:268-274. [PMID: 36591982 DOI: 10.1097/mop.0000000000001216] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
PURPOSE OF REVIEW In a child with evidence of acute kidney injury (AKI) following renal transplantation, it is important to quickly and accurately diagnose the cause to enable timely initiation of therapeutic interventions. The following article will discuss the differential diagnosis of acute graft dysfunction in paediatric kidney transplant recipients. This review will systematically guide the clinician through the common and less common causes and provide updates on current treatments. RECENT FINDINGS In patients with signs of graft dysfunction, rejection is an important cause to consider. Diagnosis of rejection relies on biopsy findings, an invasive and costly technique. Over the past 5 years, there has been a focus on noninvasive methods of diagnosing rejection, including serum and urinary biomarkers. SUMMARY This review discusses the differential diagnosis of acute graft dysfunction following transplant, with a focus on acute rejection, urinary tract infections and common viral causes, prerenal and postrenal causes, nephrotoxic medications, specifically calcineurin inhibitor toxicity, thrombotic microangiopathy and recurrence of the underlying disease. Each condition is discussed in detail, with a focus on clinical clues to the cause, incidence in the paediatric population, workup and treatment.
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Affiliation(s)
| | - Daniella Levy-Erez
- Schneider Children's Medical Center in Israel, Petah Tikva
- Tel Aviv, University School of Medicine, Tel Aviv, Israel
- Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
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27
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Hou Y, Ding T, Guan Z, Wang J, Yao R, Yu Z, Zhao X. Untargeted metabolomics reveals the preventive effect of quercetin on nephrotoxicity induced by four organophosphorus pesticide mixtures. Food Chem Toxicol 2023; 175:113747. [PMID: 36997054 DOI: 10.1016/j.fct.2023.113747] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 03/17/2023] [Accepted: 03/23/2023] [Indexed: 03/30/2023]
Abstract
This research aimed to explore the protective effect of quercetin against nephrotoxicity induced by four organophosphate pesticide mixtures (PM) using untargeted metabolomics technology in rat kidneys. Sixty male Wistar rats were randomly divided into six groups: control, low-dose quercetin treated (10 mg/kg. bw), high-dose quercetin treated (50 mg/kg. bw), PM-treated, and two dosages of quercetin + PM-treated. Metabolomics results showed that 17 differential metabolites were identified in the PM-treated group, and pathway analysis revealed that renal metabolic disorders include purine metabolism, glycerophospholipid metabolism, and vitamin B6 metabolism. When high-dose quercetin and PM-treated were administered to rats concurrently, the intensities of differential metabolites were substantially restored (p < 0.01), suggesting that quercetin can improve renal metabolic disorders caused by organophosphate pesticides (OPs). Mechanistically, quercetin could regulate the purine metabolism disorder and endoplasmic reticulum stress (ERS)-mediated autophagy induced by OPs by inhibiting XOD activity. Moreover, quercetin inhibits PLA2 activity to regulate glycerophospholipid metabolism and it could also exert antioxidant and anti-inflammatory effects to correct vitamin B6 metabolism in rat kidneys. Taken together, the high dose of quercetin (50 mg/kg.bw) has a certain protective effect on OPs-induced nephrotoxicity in rats, which provides a theoretical basis for quercetin against nephrotoxicity caused by OPs.
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28
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Lim MA, Bloom RD. How to maximize graft survival. Curr Opin Organ Transplant 2023; 28:55-63. [PMID: 36579685 DOI: 10.1097/mot.0000000000001039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
PURPOSE OF REVIEW Kidney transplant failure results in significant patient morbidity and mortality, increased financial burden and exacerbates the organ shortage faced by kidney transplant candidates. The different strategies to maximize graft survival in kidney transplant recipients is presented in this review. RECENT FINDINGS Maximizing kidney graft survival requires optimizing immunosuppression, preventing and managing recurrent disease and using general chronic kidney disease strategies to slow allograft injury. Herein, we review: 1) strategies to tailor immunosuppression to the individual patient to avoid over and underimmunosuppression, and avoid immunosuppression-related drug toxicities, 2) latest findings in the following recurrent diseases: focal segmental glomerulosclerosis, membranous nephropathy, complement-mediated kidney disease and monoclonal gammopathy of renal significance, and, 3) approaches to slow allograft injury including BP control, and the use of antiproteinuric agents and SGLT-2 inhibitors. SUMMARY The last two decades has seen significant improvement in allograft outcomes resulting from advances in immunosuppression. With the federal government's renewed focus on kidney disease and transplantation, and recent advances in biomarkers, genetic testing, big data analytics and machine learning, we hope to see further outcome improvements in the next decade.
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Affiliation(s)
- Mary Ann Lim
- Renal-Electrolyte and Hypertension Division, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
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29
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Silva RM, Leal R, Marques MG, Rodrigues L, Santos L, Romaozinho C, Alves R, Figueiredo A. Treatment of Recurrent Antineutrophil Cytoplasmic Antibody-Associated Vasculitis After Kidney Transplant With Rituximab: A Successful Case Report. EXP CLIN TRANSPLANT 2023; 21:171-174. [PMID: 36919725 DOI: 10.6002/ect.2023.0012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/16/2023]
Abstract
Antineutrophil cytoplasm antibody-associated systemic vasculitis is a rare disease that frequently leads to end-stage renal disease. Kidney transplant should be delayed until patients are in complete clinical remission for at least 6 months, but the persistence of antineutrophil cytoplasmic antibody titers should not delay transplant. Recurrence of disease after kidney transplant is rare, with only a few cases described in the literature with heterogenous clinical manifestations, therapeutic approaches, and prognosis. We describe the case of a young male patient with recurrent antineutrophil cytoplasmic antibody vasculitis, 5 years after kidney transplant, successfully treated with methylprednisolone pulses plus rituximab. Rituximab presents a new valid option for the treatment of antineutrophil cytoplasmic antibody vasculitis relapse in kidney grafts.
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Affiliation(s)
- Rita M Silva
- From the Department of Nephrology, Urology, and Kidney Transplantation, Coimbra University Hospital Center, Portugal
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30
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Bellini MI, Deurloo E, Consorti F, Herbert PE. Body mass index affects kidney transplant outcomes: A cohort study over 5 years using a steroid sparing protocol. Front Endocrinol (Lausanne) 2023; 14:1106087. [PMID: 36843609 PMCID: PMC9947147 DOI: 10.3389/fendo.2023.1106087] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Accepted: 01/26/2023] [Indexed: 02/11/2023] Open
Abstract
BACKGROUND There is controversy regarding the suitability of high body mass index (BMI) candidates accessing the transplant waitlist. PATIENTS AND METHODS Observational study on consecutive kidney transplant recipients undergoing surgery between January 2014 and March 2016 at our center. Patients were stratified according to BMI. Survival outcomes and graft function were analyzed to investigate the effect of donor's and recipient's demographic characteristics. RESULTS 396 kidney transplant recipients: 260 males, mean age 51.8 ± 15.9 years, followed up for a mean time of 5.86 ± 2.29 years. Mean BMI 26.2 ± 5.1. BMI class 1 (20 ≤ BMI ≤ 24.9) n=133, class 2 (25 ≤ BMI ≤ 29.9) n= 155, class 3 (30 ≤ BMI ≤34.9) n=53, class 4 (BMI ≥ 35) n=21, class V (BMI ≤ 19.9) n=34. Patient survival was not significantly different according to the recipient's BMI class (p=0.476); graft survival was affected (p=0.031), as well as graft function up to 2 years post-transplant and at 4 years follow up (p=0.016). At logistic regression the factors independently associated with graft loss were only donor's age (p=0.05) and BMI class of the recipient (p=0.002). CONCLUSIONS Obesity did not impact on patient's survival but affected graft function and graft loss.
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Affiliation(s)
| | - Emily Deurloo
- Renal Transplant Department, Hammersmith Hospital, Imperial College National Health System (NHS) Trust, London, United Kingdom
| | | | - Paul Elliot Herbert
- Renal Transplant Department, Hammersmith Hospital, Imperial College National Health System (NHS) Trust, London, United Kingdom
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31
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Peters K. Physiology and pathology of the C3 amplification cycle: A retrospective. Immunol Rev 2023; 313:217-224. [PMID: 36408746 PMCID: PMC10099761 DOI: 10.1111/imr.13165] [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: 11/22/2022]
Abstract
The C3 "Tickover" hypothesis, a mechanism whereby the host maintains constant surveillance of potential invading pathogens, targeting them for elimination through amplified C3b generation and C3-dependent effector mechanisms, was proposed by the late Professor Peter Lachmann in 1973. This unique insight came from a combined understanding of the complement system as it was then defined and the nature of the disease process in rare complement deficiencies and complement-driven diseases. In this review, I give a personal perspective of how understanding of "Tickover" has developed in the subsequent 50 years, culminating in the introduction into the clinic of therapeutic agents designed to combat amplification-driven disease.
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Cirillo L, Lugli G, Raglianti V, Ravaglia F, Buti E, Landini S, Becherucci F. Defining diagnostic trajectories in patients with podocytopathies. Clin Kidney J 2022; 15:2006-2019. [PMID: 36325008 PMCID: PMC9613436 DOI: 10.1093/ckj/sfac123] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2022] [Indexed: 11/29/2022] Open
Abstract
Podocytopathies are glomerular disorders in which podocyte injury drives proteinuria and progressive kidney disease. They encompass a broad spectrum of aetiologies, resulting in pathological pictures of minimal-changes, focal segmental glomerulosclerosis, diffuse mesangial sclerosis or collapsing glomerulopathy. Despite improvement in classifying podocytopathies as a distinct group of disorders, the histological definition fails to capture the relevant biological heterogeneity underlying each case, manifesting as extensive variability in disease progression and response to therapies. Increasing evidence suggests that podocytopathies can result from a single causative factor or a combination of multiple genetic and/or environmental risk factors with different relative contributions, identifying complex physiopathological mechanisms. Consequently, the diagnosis can still be challenging. In recent years, significant advances in genetic, microscopy and biological techniques revolutionized our understanding of the molecular mechanisms underlying podocytopathies, pushing nephrologists to integrate innovative information with more conventional data obtained from kidney biopsy in the diagnostic workflow. In this review, we will summarize current approaches in the diagnosis of podocytopathies, focusing on strategies aimed at elucidating the aetiology underlying the histological picture. We will provide several examples of an integrative view of traditional concepts and new data in patients with suspected podocytopathies, along with a perspective on how a reclassification could help to improve not only diagnostic pathways and therapeutic strategies, but also the management of disease recurrence after kidney transplantation. In the future, the advantages of precision medicine will probably allow diagnostic trajectories to be increasingly focused, maximizing therapeutic results and long-term prognosis.
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Affiliation(s)
- Luigi Cirillo
- Nephrology and Dialysis Unit, Meyer Children's Hospital, Florence, Italy
- Department of Biomedical, Experimental and Clinical Sciences ‘Mario Serio’, University of Florence, Florence, Italy
| | - Gianmarco Lugli
- Nephrology and Dialysis Unit, Meyer Children's Hospital, Florence, Italy
- Department of Biomedical, Experimental and Clinical Sciences ‘Mario Serio’, University of Florence, Florence, Italy
| | | | | | - Elisa Buti
- Nephrology and Dialysis Unit, Meyer Children's Hospital, Florence, Italy
| | - Samuela Landini
- Medical Genetics Unit, Meyer Children's Hospital, Florence, Italy
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Giannopoulou M, Tarassi K, Tsouka G, Christodoulidou C, Stefanidis I, Eleftheriadis T. Rituximab Administered for Recurrent Membranous Nephropathy in a Kidney Transplant Recipient Did Not Eliminate Donor-Specific Antibodies. EXP CLIN TRANSPLANT 2022; 20:695-697. [PMID: 35924746 DOI: 10.6002/ect.2022.0146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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Wang YN, Feng HY, Nie X, Zhang YM, Zou L, Li X, Yu XY, Zhao YY. Recent Advances in Clinical Diagnosis and Pharmacotherapy Options of Membranous Nephropathy. Front Pharmacol 2022; 13:907108. [PMID: 35694252 PMCID: PMC9178124 DOI: 10.3389/fphar.2022.907108] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Accepted: 04/25/2022] [Indexed: 12/12/2022] Open
Abstract
Membranous nephropathy (MN) is the most common cause of nephrotic syndrome among adults, which is the leading glomerular disease that recurs after kidney transplantation. Treatment for MN remained controversial and challenging, partly owing to absence of sensitive and specific biomarkers and effective therapy for prediction and diagnosis of disease activity. MN starts with the formation and deposition of circulating immune complexes on the outer area in the glomerular basement membrane, leading to complement activation. The identification of autoantibodies against the phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain-containing protein 7A (THSD7A) antigens illuminated a distinct pathophysiological rationale for MN treatments. Nowadays, detection of serum anti-PLA2R antibodies and deposited glomerular PLA2R antigen can be routinely applied to MN. Anti-PLA2R antibodies exhibited much high specificity and sensitivity. Measurement of PLA2R in immune complex deposition allows for the diagnosis of PLA2R-associated MN in patients with renal biopsies. In the review, we critically summarized newer diagnosis biomarkers including PLA2R and THSD7A tests and novel promising therapies by using traditional Chinese medicines such as Astragalus membranaceus, Tripterygium wilfordii, and Astragaloside IV for the treatment of MN patients. We also described unresolved questions and future challenges to reveal the diagnosis and treatments of MN. These unprecedented breakthroughs were quickly translated to clinical diagnosis and management. Considerable advances of detection methods played a critical role in diagnosis and monitoring of treatment.
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Affiliation(s)
- Yan-Ni Wang
- Faculty of Life Science & Medicine, Northwest University, Xi’an, China
| | - Hao-Yu Feng
- Faculty of Life Science & Medicine, Northwest University, Xi’an, China
| | - Xin Nie
- Faculty of Life Science & Medicine, Northwest University, Xi’an, China
| | - Ya-Mei Zhang
- Key Disciplines of Clinical Pharmacy, Clinical Genetics Laboratory, Affiliated Hospital and Clinical Medical College of Chengdu University, Chengdu, China
| | - Liang Zou
- School of Food and Bioengineering, Chengdu University, Chengdu, China
| | - Xia Li
- Faculty of Life Science & Medicine, Northwest University, Xi’an, China
- Department of General Practice, Xi’an International Medical Center Hospital, Northwest University, Xi’an, China
| | - Xiao-Yong Yu
- Department of Nephrology, Shaanxi Traditional Chinese Medicine Hospital, Xi’an, China
| | - Ying-Yong Zhao
- Faculty of Life Science & Medicine, Northwest University, Xi’an, China
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Cody E, Hooper DK. Kidney transplantation in pediatric patients with rheumatologic disorders. Curr Opin Pediatr 2022; 34:234-240. [PMID: 34954727 DOI: 10.1097/mop.0000000000001100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE OF REVIEW Providers caring for children with end-stage kidney disease from rheumatologic conditions face questions such as when to proceed with kidney transplantation, how common is disease recurrence posttransplant, how does recurrent disease impact patient and allograft outcomes, and what approaches are available to prevent and treat recurrent disease. We discuss recent developments and relevant literature that address these questions for the most common rheumatologic disorders that lead to end-stage kidney disease in childhood namely, systemic lupus erythematosus, IgA nephropathy, IgA Vasculitis/Henoch Schoenlein Purpura, and Anti-Neutrophil Cytoplasmic Antibody (ANCA)-associated vasculitis. RECENT FINDINGS Recent data suggest that children with IgA nephropathy, IgA vasculitis, and ANCA-associated vasculitis have similar patient and allograft survival to other conditions despite the risk of recurrent disease, yet those with lupus have worse posttransplant patient and allograft outcomes. A period of disease quiescence may be prudent prior to transplantation to decrease the risk of recurrence, which is associated with decreased allograft survival. Data on preventive strategies and treatment options are limited. SUMMARY It is recommended that patients with systemic rheumatologic conditions not be excluded from kidney transplantation but that patients be counseled on the risk of potential recurrent disease with its impact on transplant outcomes.
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Affiliation(s)
- Ellen Cody
- Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center
| | - David K Hooper
- Division of Nephrology and Hypertension, Department of Pediatrics, Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
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OUP accepted manuscript. Nephrol Dial Transplant 2022; 37:2090-2092. [DOI: 10.1093/ndt/gfab345] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Indexed: 11/15/2022] Open
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