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Napoletano A, Provenzano M, Maritati F, Corradetti V, Cuna V, Gessaroli E, Abenavoli C, Barbuto S, Demetri M, Ravaioli M, Comai G, La Manna G. Risk factors for IgA nephropathy recurrence and impact on graft survival in a cohort of kidney transplanted patients. Ren Fail 2025; 47:2472041. [PMID: 40050250 PMCID: PMC11892068 DOI: 10.1080/0886022x.2025.2472041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Revised: 02/19/2025] [Accepted: 02/20/2025] [Indexed: 03/12/2025] Open
Abstract
Recurrence of IgA nephropathy (IgAN) after kidney transplant (KT) appears associated with worse graft survival; thus, the identification of risk factors is worthwhile to improve pre-transplant evaluation of KT recipients and to identify the optimal treatment strategy. The aim of this study was to determine incidence, risk factors and impact on renal function and graft survival of IgAN recurrence after KT. We performed a retrospective study including 110 patients with biopsy-proven IgAN, who underwent KT at Policlinico di Sant'Orsola Hospital - University of Bologna from 2005 to 2021. IgAN recurred in 14 patients (12.7%) with a median time-to-recurrence of 59 (16-90) months. We found that a faster progression from IgAN diagnosis to end-stage kidney disease (ESKD), a younger age at ESKD, and a younger age at KT were associated with a higher risk of recurrence. During the first 2 years after KT, 24 h proteinuria was higher in patients with IgAN recurrence than in patients without (0.40 (0.11-1.8) vs 0.22 (0.18-0.37) g/day, p = 0.0003). During the follow-up period, a more rapid decline in eGFR was observed in the Recurrence group (p = 0.023). Additionally, graft survival at 10 years post-kidney transplant was significantly lower in this group (log-rank test p = 0.015). In conclusion, we found that patients with a more aggressive form of IgAN, who reached ESKD before 36 years of age, had an higher risk of recurrence in KT. Moreover we confirmed that recurrent IgAN, especially if clinically relevant, is associated with a worse graft outcome.
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Affiliation(s)
- Angelodaniele Napoletano
- Nephrology, Dialysis and Kidney Transplant Unit, IRCCS Azienda Ospedaliero-Univesitaria di Bologna, Bologna, Italy
| | - Michele Provenzano
- Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, CS, Italy
| | - Federica Maritati
- Nephrology, Dialysis and Kidney Transplant Unit, IRCCS Azienda Ospedaliero-Univesitaria di Bologna, Bologna, Italy
| | - Valeria Corradetti
- Nephrology, Dialysis and Kidney Transplant Unit, IRCCS Azienda Ospedaliero-Univesitaria di Bologna, Bologna, Italy
| | - Vania Cuna
- Nephrology, Dialysis and Kidney Transplant Unit, IRCCS Azienda Ospedaliero-Univesitaria di Bologna, Bologna, Italy
| | - Elisa Gessaroli
- Nephrology, Dialysis and Kidney Transplant Unit, IRCCS Azienda Ospedaliero-Univesitaria di Bologna, Bologna, Italy
| | - Chiara Abenavoli
- Nephrology, Dialysis and Kidney Transplant Unit, IRCCS Azienda Ospedaliero-Univesitaria di Bologna, Bologna, Italy
| | - Simona Barbuto
- Nephrology, Dialysis and Kidney Transplant Unit, IRCCS Azienda Ospedaliero-Univesitaria di Bologna, Bologna, Italy
| | - Marcello Demetri
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna, Italy
| | - Matteo Ravaioli
- Department of Medical and Surgical Sciences, University of Bologna, Italy
- Hepato-biliary Surgery and Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Giorgia Comai
- Nephrology, Dialysis and Kidney Transplant Unit, IRCCS Azienda Ospedaliero-Univesitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna, Italy
| | - Gaetano La Manna
- Nephrology, Dialysis and Kidney Transplant Unit, IRCCS Azienda Ospedaliero-Univesitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna, Italy
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Yusuf S, Alexander S, Roy S, Rebekah G, John EE, Thomas A, Eapen JJ, David VG, Varughese S. Glomerulonephritis After Renal Transplatation in South Asia - Single Center Experience Over 5 Decades. Indian J Nephrol 2025; 35:270-276. [PMID: 40060067 PMCID: PMC11883335 DOI: 10.25259/ijn_39_2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Accepted: 04/02/2024] [Indexed: 05/06/2025] Open
Abstract
Background With significant advances in the understanding of transplant immunology and a reduction in rejection rates, significant improvements in kidney allograft survival have been seen. The problem of recurrent and denovo glomerular diseases after transplantation affecting graft outcomes remains and is poorly characterized. This study aimed to analyze the incidence, characteristics, and outcomes of glomerulonephritis (GN) after kidney transplant in the Indian subcontinent. Materials and Methods Data on patients who underwent kidney transplants in our hospital from 1971 to 2018 was analyzed. Patients who had biopsy proven glomerulonephritis after transplant were included in the study. Demographic factors, characteristics of glomerulonephritis after transplant, and patient and graft outcomes were studied. Results Post-transplant glomerulonephritis was seen in 177 out of 3630 (4.8%) patients. IgA nephropathy (IgAN) was the most common type, followed by focal segmental glomerulosclerosis (FSGS) and thrombotic microangiopathy (TMA). Patients with IgAN and FSGS were younger, and native kidney disease was unknown in the majority (70% in IgAN and 40% in FSGS). Glomerulonephritis was the most common cause of graft loss. A serum creatinine level of ≥2 mg/dL at 1 year post-transplant was significantly associated with the risk of death and graft loss. In addition, the occurrence of glomerulonephritis within a year of transplant and cytomegalovirus (CMV) infection were found to be significant risk factors for death and graft loss, respectively. Conclusion Post transplant glomerulonephritis can significantly impact patient and graft outcomes. Understanding its etiology and pathogenesis is crucial to enabling its prevention and management and improving the outcomes of kidney transplantation.
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Affiliation(s)
- Sabina Yusuf
- Department of Nephrology, Christian Medical College Vellore, Ranipet Campus, Ranipet, India
| | - Suceena Alexander
- Department of Nephrology, Christian Medical College Vellore, Ranipet Campus, Ranipet, India
| | - Sanjeet Roy
- Department of General Pathology, Christian Medical College Vellore, Ranipet Campus, Ranipet, India
| | - Grace Rebekah
- Department of Biostatistics, Christian Medical College, Vellore Campus, Vellore, India
| | - Elenjickal Elias John
- Department of Nephrology, Christian Medical College Vellore, Ranipet Campus, Ranipet, India
| | - Athul Thomas
- Department of Nephrology, Christian Medical College Vellore, Ranipet Campus, Ranipet, India
| | - Jeethu Joseph Eapen
- Department of Nephrology, Christian Medical College Vellore, Ranipet Campus, Ranipet, India
| | - Vinoi George David
- Department of Nephrology, Christian Medical College Vellore, Ranipet Campus, Ranipet, India
| | - Santosh Varughese
- Department of Nephrology, Christian Medical College Vellore, Ranipet Campus, Ranipet, India
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Engen RM, Bartosh SM, Smith JM, Perkins JD, Harshman LA. Risk for graft loss in pediatric and young adult kidney transplant recipients due to recurrent IgA nephropathy. Am J Transplant 2024; 24:37-45. [PMID: 37595842 DOI: 10.1016/j.ajt.2023.08.007] [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: 04/25/2023] [Revised: 07/29/2023] [Accepted: 08/10/2023] [Indexed: 08/20/2023]
Abstract
IgA nephropathy (IgAN) is associated with a risk for posttransplant recurrence. Data are limited regarding graft loss attributable to recurrence of IgAN among pediatric and young adult kidney transplant (KT) recipients. This was a retrospective cohort study of patients aged 0 to 25 years from the Scientific Registry of Transplant Recipients who received a primary KT for IgAN. Patients with history of KT attributable to renal dysplasia were comparators. Outcomes included the incidence of graft loss attributable to IgAN recurrence, association with donor type, and posttransplant corticosteroid use. In total, 5475 transplant recipients were included, with 1915 patients with IgAN and 3560 patients with renal dysplasia. In a multivariable Cox proportional hazards model, IgAN was associated with higher risk of graft loss (adjusted hazard ratio [aHR], 1.35; 95% CI, 1.21-1.50; P < .001) compared with dysplasia. Graft loss was attributed to recurrent disease in 5.4% of patients with IgAN. In a multivariable competing risks analysis, patients with IgAN receiving a parental living-donor kidney were more likely to report graft loss from recurrent disease compared with patients with a nonparental living donor (aHR, 0.52; 95% CI, 0.31-0.91; P = .02). Posttransplant prednisone use was not associated with improved graft survival (P = .2). These data challenge existing paradigms in posttransplant management of patients with IgAN.
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Affiliation(s)
- Rachel M Engen
- University of Wisconsin Madison, Madison, Wisconsin, USA.
| | | | - Jodi M Smith
- University of Washington, Seattle, Washington DC, USA
| | - James D Perkins
- Clinical and Bio-Analytics Transplant Laboratory (CBATL), Division of Transplant Surgery, Department of Surgery, University of Washington, Seattle, Washington DC, USA
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Li Y, Tang Y, Lin T, Song T. Risk factors and outcomes of IgA nephropathy recurrence after kidney transplantation: a systematic review and meta-analysis. Front Immunol 2023; 14:1277017. [PMID: 38090563 PMCID: PMC10713786 DOI: 10.3389/fimmu.2023.1277017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2023] [Accepted: 11/09/2023] [Indexed: 12/18/2023] Open
Abstract
Background IgA nephropathy may recur in patients receiving kidney transplantation due to IgA nephropathy induced renal failure. The risk factors for recurrence are still at issue. The aim of this study was to conduct a systematic review and meta-analysis to assess risk factors and outcomes for IgA nephropathy recurrence. Methods We used PubMed, EMBASE, Cochrane Library, Web of Science, Scopus, CNKI, WanFang, VIP and CBM to search for relevant studies published in English and Chinese. Cohort or case-control studies reporting risk factors or outcomes for IgA nephropathy recurrence were included. Results Fifty-eight studies were included. Compare to no recurrence group, those with IgAN recurrence had younger age (mean difference [MD]=-4.27 years; risk ratio [RR]=0.96), younger donor age (MD=-2.19 years), shorter time from IgA nephropathy diagnosis to end stage renal disease (MD=-1.84 years; RR=0.94), shorter time on dialysis (MD=-3.14 months), lower human leukocyte-antigen (HLA) mismatches (MD=-0.11) and HLA-DR mismatches (MD=-0.13). HLA-B46 antigen (RR=0.39), anti-IL-2-R antibodies induction (RR=0.68), mycophenolate mofetil (RR=0.69), and pretransplant tonsillectomy (RR=0.43) were associated with less IgAN recurrence. Of note, male recipient gender (RR=1.17), related donor (RR=1.53), retransplantation (RR=1.43), hemodialysis (RR=1.68), no induction therapy (RR=1.73), mTOR inhibitor (RR=1.51), angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers (RR=1.63) were risk factors for IgAN recurrence. Recurrence increased the risk of graft loss (RR=2.19). Conclusions This study summarized the risk factors for recurrence of IgA nephropathy after kidney transplantation. Well-designed prospective studies are warranted for validation. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=377480, identifier CRD42022377480.
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Affiliation(s)
- Yue Li
- Department of Urology, West China Hospital, Sichuan University, Chengdu, China
- Transplant Center, West China Hospital, Sichuan University, Chengdu, China
| | - Yangming Tang
- Department of Urology, West China Hospital, Sichuan University, Chengdu, China
- Transplant Center, West China Hospital, Sichuan University, Chengdu, China
| | - Tao Lin
- Department of Urology, West China Hospital, Sichuan University, Chengdu, China
- Transplant Center, West China Hospital, Sichuan University, Chengdu, China
| | - Turun Song
- Department of Urology, West China Hospital, Sichuan University, Chengdu, China
- Transplant Center, West China Hospital, Sichuan University, Chengdu, China
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Bednarova K, Mjøen G, Hruba P, Modos I, Voska L, Kollar M, Viklicky O. A novel prognostic nomogram predicts premature failure of kidney allografts with IgA nephropathy recurrence. Nephrol Dial Transplant 2023; 38:2627-2636. [PMID: 37202220 PMCID: PMC10660147 DOI: 10.1093/ndt/gfad097] [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: 11/07/2022] [Indexed: 05/20/2023] Open
Abstract
BACKGROUND Recurrence of immunoglobulin A nephropathy (IgAN) limits graft survival in kidney transplantation. However, predictors of a worse outcome are poorly understood. METHODS Among 442 kidney transplant recipients (KTRs) with IgAN, 83 (18.8%) KTRs exhibited biopsy-proven IgAN recurrence between 1994 and 2020 and were enrolled in the derivation cohort. A multivariable Cox model predicting allograft loss based on clinical data at the biopsy and a web-based nomogram were developed. The nomogram was externally validated using an independent cohort (n = 67). RESULTS Patient age <43 years {hazard ratio [HR] 2.20 [95% confidence interval (CI) 1.41-3.43], P < .001}, female gender [HR 1.72 (95% CI 1.07-2.76), P = .026] and retransplantation status [HR 1.98 (95% CI 1.13-3.36), P = .016] were identified as independent risk factors for IgAN recurrence. Patient age <43 years [HR 2.77 (95% CI 1.17-6.56), P = .02], proteinuria >1 g/24 hours [HR 3.12 (95% CI 1.40-6.91), P = .005] and C4d positivity [HR 2.93 (95% CI 1.26-6.83), P = .013] were found to be associated with graft loss in patients with IgAN recurrence. A nomogram predicting graft loss was constructed based on clinical and histological variables, with a C statistic of 0.736 for the derivation cohort and 0.807 for the external validation cohort. CONCLUSIONS The established nomogram identified patients with recurrent IgAN at risk for premature graft loss with good predictive performance.
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Affiliation(s)
- Kamila Bednarova
- Department of Nephrology, Transplant Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
- 1st Medical Faculty, Charles University, Prague, Czech Republic
| | - Geir Mjøen
- Department of Nephrology, Oslo University Hospital, Oslo, Norway
| | - Petra Hruba
- Transplant Laboratory, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Istvan Modos
- Department of Informatics, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Ludek Voska
- Clinical and Transplant Pathology Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Marek Kollar
- Clinical and Transplant Pathology Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Ondrej Viklicky
- Department of Nephrology, Transplant Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
- Transplant Laboratory, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
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Kawabe M, Yamamoto I. Current Status and Perspectives on Recurrent IgA Nephropathy after Kidney Transplantation. Nephron Clin Pract 2023; 147 Suppl 1:9-13. [PMID: 36966530 DOI: 10.1159/000530341] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Accepted: 02/21/2023] [Indexed: 06/18/2023] Open
Abstract
IgA nephropathy (IgAN) is the most common form of glomerulonephritis worldwide. IgAN progresses to end-stage kidney disease in 20-40% of patients within 20 years of diagnosis. Kidney transplantation is the most effective option for patients with end-stage kidney disease caused by IgAN, but recurrence can occur in the transplanted kidney. The IgAN recurrence rate varies from 1% to 10% per year and varies according to the follow-up period, diagnostic modality, and biopsy criteria. Of note, studies based on protocol biopsies have reported a higher incidence of recurrence, which also occurred earlier after transplantation. In addition, recent data show that recurrence of IgAN is a more significant cause of allograft failure than previously believed. Little is known about the pathophysiology of IgAN recurrence, but several potential biomarkers have been investigated. Among them, galactose-deficient IgA1 (Gd-IgA1), IgG anti-Gd-IgA1 antibodies, and soluble CD89 could play a pivotal role in disease activity. This review aims to describe the current status of recurrent IgAN, including the incidence, clinical characteristics, risk factors, and future perspectives, with a focus on the available therapeutic approaches.
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Affiliation(s)
- Mayuko Kawabe
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan,
| | - Izumi Yamamoto
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
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El-Rifai R, Bregman A, Klomjit N, Spong R, Jackson S, Nachman PH, Riad S. Living Donor Kidney Transplant in Recipients With Glomerulonephritis: Donor Recipient Biologic Relationship and Allograft Outcomes. Transpl Int 2023; 36:11068. [PMID: 37213488 PMCID: PMC10195883 DOI: 10.3389/ti.2023.11068] [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: 11/18/2022] [Accepted: 04/12/2023] [Indexed: 05/23/2023]
Abstract
Using the Scientific Registry of Transplant Recipients, we examined the association between donor-recipient biologic relationship and long-term recipient and allograft survival among glomerulonephritis (GN) patients. Four GN types were studied: membranous nephropathy, IgA, lupus-associated nephritis, and focal segmental glomerulosclerosis (FSGS). We identified all adult primary living-donor recipients between 2000 and 2018 (n = 19,668): related (n = 10,437); unrelated (n = 9,231). Kaplan-Meier curves were generated for the recipient, death-censored graft survival and death with functioning graft through ten years post-transplant. Multivariable Cox proportional hazard models were used to examine the association between the donor-recipient relationship and outcomes of interest. There was an increased risk for acute rejection by 12 months post-transplant among the unrelated compared to the related group in IgA (10.1% vs. 6.5%, p<0.001), FSGS (12.1% vs. 10%, p-0.016), and lupus nephritis (11.8% vs. 9.2%; p-0.049). The biological donor-recipient relationship was not associated with a worse recipient or graft survival or death with functioning graft in the multivariable models. These findings are consistent with the known benefits of living-related-donor kidney transplants and counter the reports of the potential adverse impact of the donor-recipient biologic relationship on allograft outcomes.
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Affiliation(s)
- Rasha El-Rifai
- Division of Renal Diseases and Hypertension, Department of Medicine, University of Minnesota, Minneapolis, MN, United States
| | - Adam Bregman
- Division of Renal Diseases and Hypertension, Department of Medicine, University of Minnesota, Minneapolis, MN, United States
| | - Nattawat Klomjit
- Division of Renal Diseases and Hypertension, Department of Medicine, University of Minnesota, Minneapolis, MN, United States
| | - Richard Spong
- Division of Renal Diseases and Hypertension, Department of Medicine, University of Minnesota, Minneapolis, MN, United States
| | - Scott Jackson
- Complex Care Analytics, MHealth Fairview, Minneapolis, MN, United States
| | - Patrick H. Nachman
- Division of Renal Diseases and Hypertension, Department of Medicine, University of Minnesota, Minneapolis, MN, United States
| | - Samy Riad
- Division of Renal Diseases and Hypertension, Department of Medicine, University of Minnesota, Minneapolis, MN, United States
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, United States
- *Correspondence: Samy Riad,
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Khurana M, Prasad N, Behera M, Yachha M, Kushwaha R, Agarwal V, Bhadauria D, Kaul A, Patel M, Jain M. Two Decades Outcomes of Posttransplant Immunoglobulin A Nephropathy in Live Donor Renal Transplantation. Indian J Nephrol 2022; 32:312-319. [PMID: 35967532 PMCID: PMC9365001 DOI: 10.4103/ijn.ijn_234_21] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2021] [Revised: 07/20/2021] [Accepted: 08/09/2021] [Indexed: 11/10/2022] Open
Abstract
Background: The data on long-term outcomes of posttransplant immunoglobulin A nephropathy (IgAN) are confounding and vary with geography and ethnicity worldwide. We aimed to study the long-term graft outcomes of patients with posttransplant IgAN in the northern Indian cohort. Methods: The long-term graft outcomes of 51 live donor renal transplant recipients with biopsy-proven posttransplant IgAN (recurrence/de novo) were analyzed. The risk factors for graft failure in the posttransplant IgA groups were analyzed using the Cox regression analysis. Results: Out of the total of 51 patients who had posttransplant IgAN, 40 patients had a biopsy-proven native kidney IgAN. The mean duration of the clinical presentation of posttransplant IgAN was 62.4 months (5.2 years) posttransplant. Proteinuria at the time of biopsy was 3.03 ± 2.2 g/day, and 41.2% had proteinuria of more than 3 g/day at the time of biopsy. The estimated 1, 5, 10, and 20 years patient survival was 98%, 95.4%, 75.9%, and 25.2%, respectively, and the estimated 1, 5, 10, and 20 years graft survival was 98%, 88.5%, 44.6%, and 11.9%, respectively, in patients who had posttransplant IgA. Many of the traditional risk factors associated with progression in native kidney IgAN, such as the degree of proteinuria, Oxford MEST (mesangial and endocapillary hypercellularity, segmental sclerosis, and interstitial fibrosis/tubular atrophy) scoring, recipient's age, and sex were not predictive of early graft failure among patients with posttransplant IgAN. In our cohort, the only significant graft failure predictor was serum creatinine at 5 years. Chronic antibody-mediated rejection (ABMR) was seen in 21.6% of patients with posttransplant IgAN. Whether this coexistence of chronic ABMR is an incidental finding or posttransplant IgAN predisposes to chronic ABMR requires further investigation. Conclusion: Posttransplant IgAN is associated with poor long-term graft outcomes in live donor renal transplants. Proteinuria and MEST scoring were not predictive of graft failure in living donor posttransplant IgAN.
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Affiliation(s)
- Mudit Khurana
- Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Narayan Prasad
- Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Manas Behera
- Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Monika Yachha
- Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Ravi Kushwaha
- Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Vinita Agarwal
- Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Dharmendra Bhadauria
- Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Anupama Kaul
- Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Manas Patel
- Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Manoj Jain
- Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
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Zanoni F, Khairallah P, Kiryluk K, Batal I. Glomerular Diseases of the Kidney Allograft: Toward a Precision Medicine Approach. Semin Nephrol 2022; 42:29-43. [PMID: 35618394 PMCID: PMC9139085 DOI: 10.1016/j.semnephrol.2022.01.005] [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: 01/03/2023]
Abstract
The continual development of potent immunosuppressive regimens has led to a decreased incidence of acute rejection and improvement of short-term kidney allograft survival. In contrast to acute rejection, glomerular diseases of the kidney allograft are being encountered more frequently and are emerging as leading causes of late kidney allograft failure. Although data on the pathogeneses of glomerular diseases in the kidney allograft are sparse, cumulative evidence suggests that post-transplant glomerular diseases may be the result of inherited predispositions and immunologic triggers. Although studying immunologic signals and performing genome-wide association studies are ideal approaches to tackle glomerular diseases in the kidney allograft, such studies are challenging because of the lack of adequately powered cohorts. In this review, we focus on the most commonly encountered recurrent and de novo glomerular diseases in the kidney allograft. We address the important advances made in understanding the immunopathology and genetic susceptibility of glomerular diseases in the native kidney and how to benefit from such knowledge to further our knowledge of post-transplant glomerular diseases. Defining genomic and immune predictors for glomerular diseases in the kidney allograft would support novel donor-recipient matching strategies and development of targeted therapies to ultimately improve long-term kidney allograft survival.
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Affiliation(s)
- Francesca Zanoni
- Medicine, Nephrology, Columbia University Irving Medical Center, New York, NY, USA
| | | | - Krzysztof Kiryluk
- Medicine, Nephrology, Columbia University Irving Medical Center, New York, NY, USA
| | - Ibrahim Batal
- Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA,Corresponding Author: Ibrahim Batal MD, Department of Pathology and Cell Biology, Renal Division, Columbia University Irving Medical Center, 630 W 168th street, VC14-238, New York, NY 10032, Phone: 212-305-9669, Fax: 212-342-5380,
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10
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Kavanagh CR, Zanoni F, Leal R, Jain NG, Stack MN, Vasilescu ER, Serban G, Shaut C, Kamal J, Kudose S, Martinho A, Alves R, Santoriello D, Canetta PA, Cohen D, Radhakrishnan J, Appel GB, Stokes MB, Markowitz GS, D’Agati VD, Kiryluk K, Andeen NK, Batal I. Clinical Predictors and Prognosis of Recurrent IgA Nephropathy in the Kidney Allograft. GLOMERULAR DISEASES 2022; 2:42-53. [PMID: 35450416 PMCID: PMC9017582 DOI: 10.1159/000519834] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Introduction Although IgA nephropathy (IgAN) is the most common recurrent glomerulonephritis encountered in the kidney allograft, the clinical and immunogenetic characteristics remain poorly understood. We sought to study determinants and prognosis of recurrent IgAN with special focus on HLA antigens. Materials and Methods Between 2005 and 2019, we identified 282 transplanted patients with failure secondary to IgAN from two North American and one European Medical Centers, including 80 with recurrent IgAN and 202 without recurrence. Prevalence of HLA antigens was compared to external healthy controls of European ancestry (n=15,740). Graft survival was assessed by Kaplan-Meier method and log rank test. Cox proportional hazards were used for multivariable analyses. Results Compared to external controls of European ancestry, kidney transplant recipients of European ancestry with kidney failure secondary to IgAN had higher frequency of HLA-DQ5 (42% vs. 30%, OR=1.68, P=0.002) and lower frequency of HLA-DR15 (15% vs. 28%, OR=0.46, P<0.001) and HLA-DQ6 (32% vs. 45%, OR=0.59, P=0.003); however, the frequency of these HLA antigens were similar in recurrent versus non-recurring IgAN. Younger recipient age at transplantation was an independent predictor of recurrence. HLA-matching was an independent predictor for recurrent IgAN only in recipients of living-related but not deceased or living unrelated transplants. Recurrent IgAN was an independent predictor of allograft failure, along with acute rejection. In patients with recurrent IgAN, serum creatinine at biopsy, degree of proteinuria, and concurrent acute rejection were associated with inferior allograft survival. Discussion/ Conclusion Recurrent IgAN negatively affects allograft survival. Younger recipient age at transplantation is an independent predictor of recurrent IgAN, while the presence of HLA antigens associated with IgAN in the native kidney and HLA-matching in recipients of deceased or living unrelated transplants are not.
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Affiliation(s)
- Catherine R. Kavanagh
- Pediatric, Nephrology, Columbia University Irving Medical Center, Morgan Stanley Children's Hospital, New York, NY, USA
| | - Francesca Zanoni
- Medicine, Nephrology, Columbia University Irving Medical Center, New York, NY, USA
| | - Rita Leal
- Nephrology department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal,Faculty of Medicine, University of Coimbra, Portugal
| | - Namrata G. Jain
- Pediatric, Nephrology, Columbia University Irving Medical Center, Morgan Stanley Children's Hospital, New York, NY, USA
| | - Megan Nicole Stack
- Medicine, Nephrology, Oregon Health & Science University, Portland, OR, USA
| | - Elena-Rodica Vasilescu
- Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA
| | - Geo Serban
- Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA
| | - Carley Shaut
- Medicine, Nephrology, Oregon Health & Science University, Portland, OR, USA
| | - Jeanne Kamal
- Medicine, Nephrology, Columbia University Irving Medical Center, New York, NY, USA
| | - Satoru Kudose
- Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA
| | - António Martinho
- Centro de Histocompatibilidade do Centro, Instituto Português do Sangue da Transplantação, Coimbra, Portugal
| | - Rui Alves
- Nephrology department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal,Faculty of Medicine, University of Coimbra, Portugal
| | - Dominick Santoriello
- Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA
| | - Pietro A Canetta
- Medicine, Nephrology, Columbia University Irving Medical Center, New York, NY, USA
| | - David Cohen
- Medicine, Nephrology, Columbia University Irving Medical Center, New York, NY, USA
| | - Jai Radhakrishnan
- Medicine, Nephrology, Columbia University Irving Medical Center, New York, NY, USA
| | - Gerald B. Appel
- Medicine, Nephrology, Columbia University Irving Medical Center, New York, NY, USA
| | - Michael B. Stokes
- Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA
| | - Glen S. Markowitz
- Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA
| | - Vivette D. D’Agati
- Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA
| | | | - Nicole K. Andeen
- Pathology, Oregon Health & Science University, Portland, OR, USA
| | - Ibrahim Batal
- Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA
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11
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Kidney transplantation outcomes in patients with IgA nephropathy and other glomerular and non-glomerular primary diseases in the new era of immunosuppression. PLoS One 2021; 16:e0253337. [PMID: 34403416 PMCID: PMC8370606 DOI: 10.1371/journal.pone.0253337] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2020] [Accepted: 06/02/2021] [Indexed: 11/19/2022] Open
Abstract
OBJECTIVES Kidney transplant (KTx) recipients with IgAN as primary disease, were compared with recipients with other causes of renal failure, in terms of long-term outcomes. METHODS Ninety-nine KTx recipients with end-stage kidney disease (ESKD) due to IgAN, were retrospectively compared to; i/ a matched case-control group of patients with non-glomerular causes of ESKD, and ii/ four control groups with ESKD due to glomerular diseases; 44 patients with primary focal segmental glomerulosclerosis (FSGS), 19 with idiopathic membranous nephropathy (IMN), 22 with lupus nephritis (LN) and 21 with pauci-immune glomerulonephritis (PIGN). RESULTS At end of the observation period, graft function and survival, were similar between KTx recipients with IgAN and all other groups, but the rate of disease recurrence in the graft differed significantly across groups. The rate of IgAN recurrence in the graft was 23.2%, compared to 59.1% (p<0.0001) in the FSGS group, 42.1% (p = 0.17) in the IMN group, and 0% in the LN and PIGN groups (p = 0.01). IgAN recipients, who were maintained with a regimen containing tacrolimus, experienced recurrence less frequently, compared to those maintained with cyclosporine (p = 0.01). Graft loss attributed to recurrence was significantly higher in patients with FSGS versus all others. CONCLUSION Recipients with IgAN as primary disease, experienced outcomes comparable to those of recipients with other causes of ESKD. The rate of IgAN recurrence in the graft was significantly lower than the rate of FSGS recurrence, but higher than the one recorded in recipients with LN or PIGN. Tacrolimus, as part of the KTx maintenance therapy, was associated with lower rates of IgAN recurrence in the graft, compared to the rate cyclosporine.
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12
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Kurian SM, Bagsic SRS, Case J, Barrick BL, Schaffer R, Rice JC, Marsh CL. UNOS/OPTN data guided assessment of IgA nephropathy recurrence after kidney transplantation and evaluation of immunosuppressive protocols in a steroid free center. TRANSPLANTATION REPORTS 2020. [DOI: 10.1016/j.tpr.2020.100063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022] Open
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13
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Kidney transplantation for primary glomerulonephritis: Recurrence risk and graft outcomes with related versus unrelated donors. Transplant Rev (Orlando) 2020; 35:100584. [PMID: 33069562 DOI: 10.1016/j.trre.2020.100584] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2020] [Revised: 10/06/2020] [Accepted: 10/09/2020] [Indexed: 11/20/2022]
Abstract
Primary glomerulonephritis can recur after kidney transplantation and may jeopardize the survival of the renal allograft. The risks of living-related kidney transplantation remain controversial in this group of patients. Living related transplantation offers potentially better HLA matching, therefore improve the long-term graft survival. However, the concern for increased rates of recurrence of the primary glomerulonephritis in the transplanted kidney from living related donors complicates the selection of donors. With the recent dramatic rise in the use of paired kidney exchange, there is now often the option of having a living related donor donate through a paired exchange. This raises the question of whether patients with primary glomerulonephritis should receive living donor kidneys through paired kidney exchange programs to obtain the benefits of a living donor kidney transplant while also reducing the risk of recurrent glomerulonephritis. Our review of the literature suggests that although the recurrence of primary glomerulonephritis occurs more often when donation occurs from a living related donor as compared to an unrelated donor, the graft survival advantage of living related donation is generally maintained despite the recurrence. We suggest that despite the increased risk of recurrence, living related donation should not be avoided in patients with primary glomerulonephritis as the cause of their end-stage renal disease.
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14
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Kawabe M, Yamamoto I, Yamakawa T, Katsumata H, Isaka N, Katsuma A, Nakada Y, Kobayashi A, Koike K, Ueda H, Tanno Y, Koike Y, Miki J, Yamada H, Kimura T, Ohkido I, Tsuboi N, Yamamoto H, Kojima H, Yokoo T. Association Between Galactose-Deficient IgA1 Derived From the Tonsils and Recurrence of IgA Nephropathy in Patients Who Underwent Kidney Transplantation. Front Immunol 2020; 11:2068. [PMID: 33013875 PMCID: PMC7494805 DOI: 10.3389/fimmu.2020.02068] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Accepted: 07/29/2020] [Indexed: 11/18/2022] Open
Abstract
Background: Recurrence of IgA nephropathy (IgAN) in the transplanted kidney is associated with graft survival, but no specific treatment is available. Tonsillectomy (TE) reportedly arrests the progression of IgAN in the native kidney. Thus, we conducted a single-center retrospective cohort study to evaluate the effect of TE prior to IgAN recurrence. Methods: Of the 36 patients with biopsy-proven IgAN who underwent kidney transplantation, 27 were included in this study. Nine patients underwent TE at 1 year after kidney transplantation (group 1), and the remaining 18 did not undergo TE (group 2). Results: The rate of histological IgAN recurrence was significantly lower in group 1 than in group 2 (11.1 vs. 55.6%, log-rank p = 0.046). In addition, half of the recurrent patients in group 2 exhibited active lesions, compared to none in group 1. Serum Gd-IgA1 levels decreased after TE in group 1, whereas they remained stable or increased slightly in group 2. In the recurrent cases, IgA and Gd-IgA1 were found in the germinal center in addition to the mantle zone of tonsils. Finally, mesangial IgA and Gd-IgA1 immunoreactivity was reduced after TE in some cases. Conclusion: Our data suggest that TE at 1 year after kidney transplantation might be associated with the reduced rate of histological IgAN recurrence. TE arrested or reduced serum Gd-IgA1 and mesangial Gd-IgA1 immunoreactivity. Therefore, we generated a hypothesis that serum Gd-IgA1 derived from the tonsils may play a pivotal role in the pathogenesis of IgAN. Based on these findings, we need to conduct verification in a prospective randomized controlled trial.
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Affiliation(s)
- Mayuko Kawabe
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Izumi Yamamoto
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Takafumi Yamakawa
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Haruki Katsumata
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Nao Isaka
- Department of Otorhinolaryngology, The Jikei University School of Medicine, Tokyo, Japan
| | - Ai Katsuma
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Yasuyuki Nakada
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Akimitsu Kobayashi
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Kentaro Koike
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Hiroyuki Ueda
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Yudo Tanno
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Yusuke Koike
- Department of Urology, The Jikei University School of Medicine, Tokyo, Japan
| | - Jun Miki
- Department of Urology, The Jikei University School of Medicine, Tokyo, Japan
| | - Hiroki Yamada
- Department of Urology, The Jikei University School of Medicine, Tokyo, Japan
| | - Takahiro Kimura
- Department of Urology, The Jikei University School of Medicine, Tokyo, Japan
| | - Ichiro Ohkido
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Nobuo Tsuboi
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Hiroyasu Yamamoto
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Hiromi Kojima
- Department of Otorhinolaryngology, The Jikei University School of Medicine, Tokyo, Japan
| | - Takashi Yokoo
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
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15
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Infante B, Rossini M, Di Lorenzo A, Coviello N, Giuseppe C, Gesualdo L, Giuseppe G, Stallone G. Recurrence of immunoglobulin A nephropathy after kidney transplantation: a narrative review of the incidence, risk factors, pathophysiology and management of immunosuppressive therapy. Clin Kidney J 2020; 13:758-767. [PMID: 33123355 PMCID: PMC7577761 DOI: 10.1093/ckj/sfaa060] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2019] [Accepted: 03/18/2020] [Indexed: 01/04/2023] Open
Abstract
Glomerulonephritis (GN) is the underlying cause of end-stage renal failure in 30–50% of kidney transplant recipients. It represents the primary cause of end-stage renal disease for 25% of the dialysis population and 45% of the transplant population. For patients with GN requiring renal replacement therapy, kidney transplantation is associated with superior outcomes compared with dialysis. Recurrent GN was previously considered to be a minor contributor to graft loss, but with the prolongation of graft survival, the effect of recurrent disease on graft outcome assumes increasing importance. Thus the extent of recurrence of original kidney disease after kidney transplantation has been underestimated for several reasons. This review aims to provide updated knowledge on one particular recurrent renal disease after kidney transplantation, immunoglobulin A nephropathy (IgAN). IgAN is one of the most common GNs worldwide. The pathogenesis of IgAN is complex and remains incompletely understood. Evidence to date is most supportive of a several hit hypothesis. Biopsy is mandatory not only to diagnose the disease in the native kidney, but also to identify and characterize graft recurrence of IgAN in the kidney graft. The optimal therapy for IgAN recurrence in the renal graft is unknown. Supportive therapy aiming to reduce proteinuria and control hypertension is the mainstream, with corticosteroids and immunosuppressive treatment tailored for certain subgroups of patients experiencing a rapidly progressive course of the disease with active lesions on renal biopsy and considering safety issues related to infectious complications.
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Affiliation(s)
- Barbara Infante
- Department of Medical and Surgical Sciences, Nephrology, Dialysis and Transplantation Unit, University of Foggia, Foggia, Italy
| | - Michele Rossini
- Department of Emergency and Organ Transplantation, Nephrology, Dialysis and Transplantation Unit, University of Bari "Aldo Moro", Bari, Italy
| | - Adelaide Di Lorenzo
- Department of Medical and Surgical Sciences, Nephrology, Dialysis and Transplantation Unit, University of Foggia, Foggia, Italy
| | - Nicola Coviello
- Department of Medical and Surgical Sciences, Nephrology, Dialysis and Transplantation Unit, University of Foggia, Foggia, Italy
| | - Castellano Giuseppe
- Department of Medical and Surgical Sciences, Nephrology, Dialysis and Transplantation Unit, University of Foggia, Foggia, Italy
| | - Loreto Gesualdo
- Department of Emergency and Organ Transplantation, Nephrology, Dialysis and Transplantation Unit, University of Bari "Aldo Moro", Bari, Italy
| | | | - Giovanni Stallone
- Department of Medical and Surgical Sciences, Nephrology, Dialysis and Transplantation Unit, University of Foggia, Foggia, Italy
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16
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Zhang J, Chen GD, Qiu J, Liu GC, Chen LZ, Fu K, Wu ZX. Graft failure of IgA nephropathy in renal allografts following living donor transplantation: predictive factor analysis of 102 biopsies. BMC Nephrol 2019; 20:446. [PMID: 31796001 PMCID: PMC6889192 DOI: 10.1186/s12882-019-1628-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2019] [Accepted: 11/18/2019] [Indexed: 11/10/2022] Open
Abstract
Background To investigate predictive factors related to graft failure of IgA nephropathy(IgAN) in renal allografts following living donor transplantation. Methods We identified a series of 102 biopsies diagnosed as IgAN in renal allografts following living donor transplantation from July 2004 to January 2017 at our center, and assess the predict value of the Lee’s classification and the 2009 Oxford classification in IgAN in renal allografts, clinical, ultrasonic and pathological characteristics at biopsy and the outcomes were retrospectively analyzed. Results The 5-year graft cumulative survival rate after transplantation was 91.4%. The 4-year graft cumulative survival rate after biopsy diagnosis of IgAN in renal allografts was 59.6%. The mean time ± SD to disease was 4.7 ± 3.5 years. The color doppler ultrasound and blood flow imagine showed the echo enhancement, the reduced blood flow distribution, the reduced peak systolic velocity of main renal artery, and the increased resistance index of arcuate renal artery were valuable in evaluating the graft dysfunction. The Cox multivariate analysis revealed that the 24-h urinary protein level (HR 1.6 for 1-g increase, 95%CI 1.2–2.0), estimated glomerular filtration rate (eGFR) (HR 1.0 for 1-mL/min/1.73 m^2 decline, 95%CI 1.0–1.1), and mesangial C1q deposition (HR 3.0, 95%CI 1.2–7.4) at biopsy were independent predictive factors of graft failure of IgAN in renal allografts. Conclusions IgAN in renal allografts occurred frequently within 5 years after transplantation. The risk of graft failure should be taken seriously in patients who exhibit heavy proteinuria and/or a declined eGFR as the initial symptoms; a high lesion grade (grade IV-V of Lee’s classification) and/or mesangial C1q deposition may also indicated a poor outcome.
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Affiliation(s)
- Jin Zhang
- Department of Urology, Guangzhou Women and Children's Medical Center, Guangzhou, 510000, China
| | - Guo-Dong Chen
- Department of Organ Transplant, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510000, China
| | - Jiang Qiu
- Department of Organ Transplant, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510000, China.
| | - Guo-Chang Liu
- Department of Urology, Guangzhou Women and Children's Medical Center, Guangzhou, 510000, China
| | - Li-Zhong Chen
- Department of Organ Transplant, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510000, China
| | - Kai Fu
- Department of Urology, Guangzhou Women and Children's Medical Center, Guangzhou, 510000, China
| | - Zi-Xuan Wu
- Department of Organ Transplant, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510000, China
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17
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Lim WH, Shingde M, Wong G. Recurrent and de novo Glomerulonephritis After Kidney Transplantation. Front Immunol 2019; 10:1944. [PMID: 31475005 PMCID: PMC6702954 DOI: 10.3389/fimmu.2019.01944] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2019] [Accepted: 08/01/2019] [Indexed: 12/13/2022] Open
Abstract
The prevalence, pathogenesis, predictors, and natural course of patients with recurrent glomerulonephritis (GN) occurring after kidney transplantation remains incompletely understood, including whether there are differences in the outcomes and advances in the treatment options of specific GN subtypes, including those with de novo GN. Consequently, the treatment options and approaches to recurrent disease are largely extrapolated from the general population, with responses to these treatments in those with recurrent or de novo GN post-transplantation poorly described. Given a greater understanding of the pathogenesis of GN and the development of novel treatment options, it is conceivable that these advances will result in an improved structure in the future management of patients with recurrent or de novo GN. This review focuses on the incidence, genetics, characteristics, clinical course, and risk of allograft failure of patients with recurrent or de novo GN after kidney transplantation, ascertaining potential disparities between “high risk” disease subtypes of IgA nephropathy, idiopathic membranous glomerulonephritis, focal segmental glomerulosclerosis, and membranoproliferative glomerulonephritis. We will examine in detail the management of patients with high risk GN, including the pre-transplant assessment, post-transplant monitoring, and the available treatment options for disease recurrence. Given the relative paucity of data of patients with recurrent and de novo GN after kidney transplantation, a global effort in collecting comprehensive in-depth data of patients with recurrent and de novo GN as well as novel trial design to test the efficacy of specific treatment strategy in large scale multicenter randomized controlled trials are essential to address the knowledge deficiency in this disease.
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Affiliation(s)
- Wai H Lim
- Department of Renal Medicine, Sir Charles Gairdner Hospital, Perth, WA, Australia.,School of Medicine, University of Western Australia, Perth, WA, Australia
| | - Meena Shingde
- NSW Health Pathology, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, NSW, Australia
| | - Germaine Wong
- Sydney School of Public Health, University of Sydney, Sydney, NSW, Australia.,Centre for Transplant and Renal Research, Westmead Hospital, Sydney, NSW, Australia.,Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, NSW, Australia
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18
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Moroni G, Belingheri M, Frontini G, Tamborini F, Messa P. Immunoglobulin A Nephropathy. Recurrence After Renal Transplantation. Front Immunol 2019; 10:1332. [PMID: 31275309 PMCID: PMC6593081 DOI: 10.3389/fimmu.2019.01332] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2019] [Accepted: 05/28/2019] [Indexed: 12/28/2022] Open
Abstract
IgA nephropathy (IgAN) is the most common primary glomerular disease worldwide. The disease generally runs an indolent course but may lead to ESRD in 20-30% of patients in 20 years or more after diagnosis. Patients with IgA nephropathy are ideal candidates for renal transplant because they are generally relatively young and with few comorbidities. Their graft survival is better or comparable to that of controls at 10 years, though few data are available after 10 years of follow-up. Recurrence of the original disease in the graft is a well-known complication of transplant in IgAN and is a significant cause of deterioration of graft function. Recurrent IgAN rarely manifests clinically before 3 years post transplantation. Recurrence rate is estimated to be around 30% with considerable differences among different series. Despite these factors there is no certain recurrence predictor, young age at renal transplant, rapid progression of the original disease and higher levels of circulating galactose-deficient IgA1 and IgA-IgG immune complexes are all associated with a higher rate of recurrence. Which pathogenetic mechanisms are responsible for the progression of the recurrence to graft function deterioration, and what therapy can prevent or slow down the progression of the disease in the graft, are open questions. The aim of this review is to describe the clinical outcome of renal transplantation in IgA patients with attention to the rate and the predictors of recurrence and to discuss the available therapeutic options for the management of recurrence.
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Affiliation(s)
- Gabriella Moroni
- Dialysis, and Renal Transplant Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Mirco Belingheri
- Dialysis, and Renal Transplant Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Giulia Frontini
- Dialysis, and Renal Transplant Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Francesco Tamborini
- Dialysis, and Renal Transplant Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Piergiorgio Messa
- Dialysis, and Renal Transplant Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.,Department of Clinical Science and Community, Università degli Studi di Milano, Milan, Italy
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19
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Lee KW, Kim KS, Lee JS, Yoo H, Kim K, Park JB, Kwon GY, Kim SJ. Impact of Induction Immunosuppression on the Recurrence of Primary IgA Nephropathy. Transplant Proc 2019; 51:1491-1495. [PMID: 31010698 DOI: 10.1016/j.transproceed.2019.01.115] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2018] [Accepted: 01/04/2019] [Indexed: 10/27/2022]
Abstract
OBJECTIVE The objective of this study was to analyze the impact of induction immunosuppression on the incidence of recurrent IgA nephropathy (IgAN). METHODS We conducted recurrence-free survival analysis of recipients of a first kidney transplant for IgAN who received a graft between 1995 and 2015. Kaplan-Meier and Cox regression analyses were used to sort the significant risk factors for recurrence. A total of 226 recipients with biopsy-proven IgAN received a kidney transplant, and 218 recipients were enrolled. RESULTS Among the recipients, 29 cases of IgAN recurrence were observed. The recipients were categorized into 3 groups according to induction immunosuppression: no induction (group 1, n = 72), anti-CD25 (group 2, n = 86), and antithymocyte globulin (ATG, group 3, n = 60). The 5- and 10-year cumulative IgAN recurrence rates were 9.7% and 21.0%, respectively. Recipients receiving ATG (group 3) exhibited significantly higher 4- and 5-year recurrence-free graft survival rates (both 96.4%) than recipients who received anti-CD25 (group 2, both 85.1%, P = .03). However, the induction therapy used (ATG or basiliximab) was not the risk factor for IgAN recurrence. CONCLUSIONS Therefore, we concluded that ATG induction seems to postpone IgAN recurrence. These findings should be evaluated with well-designed prospective studies.
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Affiliation(s)
- Kyo Won Lee
- Department of Surgery, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Korea
| | - Kyeong Sik Kim
- Department of Surgery, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Korea
| | - Ji Soo Lee
- Department of Surgery, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Korea
| | - Heejin Yoo
- Biostatistics and Clinical Epidemiology Center, Samsung Medical Center, Seoul, Korea
| | - Kyunga Kim
- Biostatistics and Clinical Epidemiology Center, Samsung Medical Center, Seoul, Korea
| | - Jae Berm Park
- Department of Surgery, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Korea.
| | - Ghee Young Kwon
- Department of Pathology, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Korea
| | - Sung Joo Kim
- Department of Surgery, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Korea
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20
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Jo HA, Han SS, Lee S, Kim JY, Yang SH, Lee H, Yang JS, Lee JP, Joo KW, Lim CS, Kim YS, Ahn C, Han JS, Kim DK. The association of tumor necrosis factor superfamily 13 with recurrence of immunoglobulin A nephropathy in living related kidney transplantation. BMC Nephrol 2019; 20:33. [PMID: 30704417 PMCID: PMC6357388 DOI: 10.1186/s12882-019-1222-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2018] [Accepted: 01/18/2019] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND An increasing amount of evidence has demonstrated an association between an increase in the level of tumor necrosis factor superfamily 13 (TNFSF13) and immunoglobulin A nephropathy (IgAN) progression. We aimed to evaluate if the level of pre-transplant serum TNFSF13 is predictive of IgAN recurrence after kidney transplantation. METHODS This analysis was based on the clinical and laboratory data of 69 patients with IgAN who underwent first kidney transplantation with no evidence of mesangial IgA deposits in zero-time transplantation biopsy. We measured pre-transplant serum TNFSF13, total IgA, and galactose-deficient IgA1 levels. RESULTS The recurrence rate of IgAN over a median follow-up duration of 5.1 years was 15.9% (11/69 patients), with a mean time to the first recurrence of 1.7 years. The high pre-transplant TNFSF13 level was associated with IgAN recurrence after kidney transplantation among patients who received a graft from a living related donor. CONCLUSIONS This study highlights association of TNFSF13 levels in recurrent IgAN patients who undergo living related donor transplantation. Further research is needed to clarify mechanisms by which TNFSF13 affects the recurrence of IgA nephropathy.
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Affiliation(s)
- Hyung Ah Jo
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
- Department of Internal Medicine, Inje University Ilsan Paik Hospital, Ilsan, Republic of Korea
| | - Seung Seok Han
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
- Kidney Research Institute, Seoul National University, Seoul, Republic of Korea
| | - Sunhwa Lee
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
- Kidney Research Institute, Seoul National University, Seoul, Republic of Korea
| | - Joo Young Kim
- Kidney Research Institute, Seoul National University, Seoul, Republic of Korea
| | - Seung Hee Yang
- Kidney Research Institute, Seoul National University, Seoul, Republic of Korea
| | - Hajeong Lee
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
- Kidney Research Institute, Seoul National University, Seoul, Republic of Korea
| | - Jae Seok Yang
- Transplantation Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
- Department of Surgery, Transplantation Center, Seoul National University Hospital, Seoul, Republic of Korea
| | - Jung Pyo Lee
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
- Kidney Research Institute, Seoul National University, Seoul, Republic of Korea
- Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Republic of Korea
| | - Kwon Wook Joo
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
- Kidney Research Institute, Seoul National University, Seoul, Republic of Korea
| | - Chun Soo Lim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
- Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Republic of Korea
| | - Yon Su Kim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
- Kidney Research Institute, Seoul National University, Seoul, Republic of Korea
| | - Curie Ahn
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
- Transplantation Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jin Suk Han
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
- Kidney Research Institute, Seoul National University, Seoul, Republic of Korea
| | - Dong Ki Kim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
- Kidney Research Institute, Seoul National University, Seoul, Republic of Korea
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Park S, Baek CH, Cho H, Yu MY, Kim YC, Go H, Kim YH, Lee JP, Min SI, Ha J, Moon KC, Kim YS, Ahn C, Park SK, Lee H. Glomerular crescents are associated with worse graft outcome in allograft IgA nephropathy. Am J Transplant 2019; 19:145-155. [PMID: 29718591 DOI: 10.1111/ajt.14908] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2018] [Revised: 04/04/2018] [Accepted: 04/20/2018] [Indexed: 01/25/2023]
Abstract
The prognosis of patients with allograft IgA nephropathy (IgAN) requires further investigation. We performed a bicenter retrospective cohort study on kidney transplant recipients diagnosed with IgAN in allograft biopsy. Recipients without allograft IgAN but with known IgAN before transplantation were included as the control group. We investigated the associations between clinicopathological characteristics, including allograft crescents, and the risk of death-censored graft failure. In total, 1256 IgAN patients in both pre- and posttransplant stages were included. Among them, 559 were diagnosed with allograft IgAN, which was a time-dependent risk factor for worse prognosis (adjusted hazard ratio = 5.009 [3.610-6.951]; P < .001) during a median of 8.1 years of follow-up. Of the patients with allograft IgAN, 88 (15.9%) had glomerular crescents, including 40 patients (7.2%) with >10% crescent formation in the total biopsied glomeruli. The presence of glomerular crescents in IgAN was associated with a worse graft prognosis, and the association was still valid with the C scores of the current Oxford classification. In conclusion, allograft IgAN is a time-dependent event and is associated with worse graft outcomes. The pathological characteristics of allograft, particularly the degree of glomerular crescent formation, may represent important risk factors for a poor prognosis.
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Affiliation(s)
- Sehoon Park
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.,Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea
| | - Chung Hee Baek
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hyunjeong Cho
- Department of Internal Medicine, Chungbuk National University Hospital, Chungcheongbukdo, Korea
| | - Mi-Yeon Yu
- Kidney Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Yong Chul Kim
- Kidney Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Heounjeong Go
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Young Hoon Kim
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jung Pyo Lee
- Kidney Research Institute, Seoul National University College of Medicine, Seoul, Korea.,Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea
| | - Sang Il Min
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Jongwon Ha
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Kyung Chul Moon
- Department of Pathology, Seoul National University Hospital, Seoul, Korea
| | - Yon Su Kim
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.,Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.,Kidney Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Curie Ahn
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.,Kidney Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Su-Kil Park
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hajeong Lee
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.,Kidney Research Institute, Seoul National University College of Medicine, Seoul, Korea
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22
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Zhang J, Qiu J, Chen GD, Wang CX, Wang C, Yu SJ, Chen LZ. Etiological analysis of graft dysfunction following living kidney transplantation: a report of 366 biopsies. Ren Fail 2018; 40:219-225. [PMID: 29619905 PMCID: PMC6014316 DOI: 10.1080/0886022x.2018.1455592] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2017] [Revised: 01/03/2018] [Accepted: 03/15/2018] [Indexed: 11/18/2022] Open
Abstract
AIM The aim of this study is to investigate the clinical features of graft dysfunction following living kidney transplantation and to assess its causes. METHODS We retrospectively analyzed a series of 366 living kidney transplantation indication biopsies with a clear etiology and diagnosis from July 2003 to June 2016 at our center. The classifications and diagnoses were performed based on clinical and pathological characteristics. All biopsies were evaluated according to the Banff 2007 schema. RESULTS Acute rejection (AR) occurred in 85 cases (22.0%), chronic rejection (CR) in 62 cases (16.1%), borderline rejection (BR) in 12 cases (3.1%), calcineurin inhibitor (CNI) toxicity damage in 41 cases (10.6%), BK virus-associated nephropathy (BKVAN) in 43 cases (11.1%), de novo or recurrent renal diseases in 134 cases (34.7%), and other causes in nine cases (2.3%); additionally, 20 cases had two simultaneous causes. The 80 cases with IgA nephropathy (IgAN) had the highest incidence (59.7%) of de novo or recurrent renal diseases. After a mean ± SD follow up of 3.7 ± 2.3 years, the 5-year graft cumulative survival rates of AR, CR, CNI toxicity, BKVAN, and de novo or recurrent renal diseases were 60.1%, 31.2%, 66.6%, 66.9%, and 67.1%, respectively. CONCLUSIONS A biopsy is helpful for the diagnosis of graft dysfunction. De novo or recurrent renal disease, represented by IgAN, is a major cause of graft dysfunction following living kidney transplantation.
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Affiliation(s)
- Jin Zhang
- Department of Organ Transplant, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Jiang Qiu
- Department of Organ Transplant, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Guo-Dong Chen
- Department of Organ Transplant, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Chang-Xi Wang
- Department of Organ Transplant, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Chang Wang
- Department of Organ Transplant, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Shuang-Jin Yu
- Department of Organ Transplant, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Li-Zhong Chen
- Department of Organ Transplant, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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23
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Kofman T, Oniszczuk J, Lang P, Grimbert P, Audard V. [Current insights about recurrence of glomerular diseases after renal transplantation]. Nephrol Ther 2018; 14:179-188. [PMID: 29706414 DOI: 10.1016/j.nephro.2018.03.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Recurrence of glomerular disease after renal transplantation is a frequent cause of graft loss. Incidence, risk factors and outcome of recurrence are widely due to the underlying glomerular disease. Graft biopsy analysis is required to confirm the definitive diagnosis of recurrence and to start an appropriate therapy that, in some cases, remains challenging to prevent graft failure. Increased use of protocol biopsy and recent advances in our understanding of the pathogenesis of some glomerular diseases with the identification of some relevant biomarkers provide a unique opportunity to initiate kidney-protective therapy at early stages of recurrence on the graft. This review summarizes our current knowledge on the management of many recurrent primary and secondary glomerulonephritis after kidney transplantation.
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Affiliation(s)
- Tomek Kofman
- Service de néphrologie et transplantation, hôpital Henri-Mondor, avenue du Maréchal-de-Lattre-de-Tassigny, 94010 Créteil cedex, France; Institut francilien de recherche en néphrologie et transplantation (IFRNT), université Paris Est-Créteil (Upec), avenue du Maréchal-de-Lattre-de-Tassigny, 94010 Créteil cedex, France
| | - Julie Oniszczuk
- Service de néphrologie et transplantation, hôpital Henri-Mondor, avenue du Maréchal-de-Lattre-de-Tassigny, 94010 Créteil cedex, France; Institut francilien de recherche en néphrologie et transplantation (IFRNT), université Paris Est-Créteil (Upec), avenue du Maréchal-de-Lattre-de-Tassigny, 94010 Créteil cedex, France
| | - Philippe Lang
- Service de néphrologie et transplantation, hôpital Henri-Mondor, avenue du Maréchal-de-Lattre-de-Tassigny, 94010 Créteil cedex, France; Institut francilien de recherche en néphrologie et transplantation (IFRNT), université Paris Est-Créteil (Upec), avenue du Maréchal-de-Lattre-de-Tassigny, 94010 Créteil cedex, France
| | - Philippe Grimbert
- Service de néphrologie et transplantation, hôpital Henri-Mondor, avenue du Maréchal-de-Lattre-de-Tassigny, 94010 Créteil cedex, France; Institut francilien de recherche en néphrologie et transplantation (IFRNT), université Paris Est-Créteil (Upec), avenue du Maréchal-de-Lattre-de-Tassigny, 94010 Créteil cedex, France
| | - Vincent Audard
- Service de néphrologie et transplantation, hôpital Henri-Mondor, avenue du Maréchal-de-Lattre-de-Tassigny, 94010 Créteil cedex, France; Institut francilien de recherche en néphrologie et transplantation (IFRNT), université Paris Est-Créteil (Upec), avenue du Maréchal-de-Lattre-de-Tassigny, 94010 Créteil cedex, France.
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24
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Early post-transplant serum IgA level is associated with IgA nephropathy recurrence after kidney transplantation. PLoS One 2018; 13:e0196101. [PMID: 29694420 PMCID: PMC5919069 DOI: 10.1371/journal.pone.0196101] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2017] [Accepted: 04/08/2018] [Indexed: 01/02/2023] Open
Abstract
IgA nephropathy (IgAN), the most frequent primary glomerulonephritis, affects young patients and is associated with a high risk of progression to end-stage renal disease. Consequently, patients with IgAN constitute an important proportion of candidates for kidney transplantation. Several studies showed a significant risk of IgAN recurrence on kidney graft, but the risks factors for recurrence remain to be accurately evaluated. Indeed, early identification of at risk patients may allow the optimization of treatment and the reduction of recurrence rate on the graft. In the present work, we studied the relationship between post-transplant serum IgA (sIgA) levels and the risk of IgAN recurrence after kidney transplantation. Recipients with IgAN had higher levels of sIgA as compared to patients with other nephropathies (p<0.05). The prevalence of IgAN recurrence was 20.8% during the period of analysis (mean follow-up of 6 ± 3.2 years). Serum IgA levels at M6, M12 and M24 post-transplant were significantly higher in patients with IgAN recurrence as compared to those without (p = 0.009, p = 0.035 and p = 0.029, respectively). Using receiver operating curve (ROC), sIgA at M6 and M12 post-transplant were significantly associated with IgAN recurrence (AUC = 0.771, p = 0.004 and AUC = 0.767, p = 0.016, respectively), while serum creatinine and proteinuria were not. Serum IgA level at month 6 was significantly associated with the occurrence of post-transplant IgA recurrence, whether it was analyzed as a continuous or a categorical variable. After successive adjustment on age, gender and proteinuria, sIgA remained a significant risk factor of post-transplant IgAN recurrence. Finally, survival free of IgAN recurrence was significantly better in patients with sIgA<222 mg/dL at month 6 as compare to IgAN patients with sIgA≥222 mg/dL (p = 0.03). Thus, the present work supports a link between post-transplant sIgA levels and IgAN recurrence and suggests that sIgA may be a valuable predictive biomarker of IgAN recurrence in kidney transplant recipients.
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25
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Deng R, Dai Y, Zhang H, Liu L, Li J, Xiong Y, Deng S, Fu Q, Wang C. Higher Incidence of Renal Allograft Glomerulonephritis in Living-Related Donor Kidney Transplantation. Transplant Proc 2018; 50:2421-2425. [PMID: 30316370 DOI: 10.1016/j.transproceed.2018.03.050] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2018] [Accepted: 03/06/2018] [Indexed: 12/17/2022]
Abstract
Glomerulonephritis recurrence has emerged as one of the leading causes of allograft loss. We aimed to investigate the effect of living-related and deceased donation on the incidence of renal allograft glomerulonephritis and its effect on renal allograft survival. METHODS Adult renal allograft recipients with primary glomerulonephritis were enrolled. Transplantation date was from Feb 2004 to Dec 2015. Exclusion criteria included combined organ transplantation, structural abnormality, diabetic nephropathy, hypertension nephropathy, obstructive nephropathy, and primary uric acid nephropathy. The incidence of biopsy-proven allograft glomerulonephritis was compared between the living-related donor group and the deceased donor group. Graft survival was assessed with Kaplan-Meier method, and Cox proportional hazard model was used to evaluate the effect of posttransplant glomerulonephritis on graft outcome. RESULTS There were 525 living-related donor kidney transplant recipients (LRKTx) and 456 deceased donor kidney transplant recipients (DDKTx) enrolled. The incidence of IgA nephropathy was 8.8% in the LRKTx group and 1.3% in the DDKTx group (P < .001); the incidence of focal segmental glomerulosclerosis (FSGS) was 3.8% in the LRKTx group and 1.5% in the DDKTx group (P = .03). FSGS increased the risk of graft failure compared with non-FSGS (hazard ratio [HR], 3.703 [1.459-9.397]; P = .006). IgA nephropathy increased the risk of graft failure by over 5 times 5 years after kidney transplantation compared with non-IgA nephropathy, but it did not affect early allograft survival (HR for ≥5 years, 6.139; 95% CI, 1.766-21.345; P = .004; HR for <5 years, 0.385 [0.053-2.814]; P = .35). CONCLUSIONS Higher incidence of IgA nephropathy and FSGS in renal allograft was observed in living-related donor kidney transplantation compared with deceased donor kidney transplantation. De novo or recurrent IgA nephropathy and FSGS impaired long-term renal allograft survival.
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Affiliation(s)
- R Deng
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Y Dai
- Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
| | - H Zhang
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - L Liu
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - J Li
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Y Xiong
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - S Deng
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Q Fu
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
| | - C Wang
- Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory on Organ Donation and Transplant Immunology, Guangzhou, China.
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26
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Abbas F, El Kossi M, Jin JK, Sharma A, Halawa A. Recurrence of primary glomerulonephritis: Review of the current evidence. World J Transplant 2017; 7:301-316. [PMID: 29312859 PMCID: PMC5743867 DOI: 10.5500/wjt.v7.i6.301] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2017] [Revised: 09/24/2017] [Accepted: 11/22/2017] [Indexed: 02/05/2023] Open
Abstract
In view of the availability of new immunosuppression strategies, the recurrence of allograft glomerulonephritis (GN) are reported to be increasing with time post transplantation. Recent advances in understanding the pathogenesis of the GN recurrent disease provided a better chance to develop new strategies to deal with the GN recurrence. Recurrent GN diseases manifest with a variable course, stubborn behavior, and poor response to therapy. Some types of GN lead to rapid decline of kidney function resulting in a frustrating return to maintenance dialysis. This subgroup of aggressive diseases actually requires intensive efforts to ascertain their pathogenesis so that strategy could be implemented for better allograft survival. Epidemiology of native glomerulonephritis as the cause of end-stage renal failure and subsequent recurrence of individual glomerulonephritis after renal transplantation was evaluated using data from various registries, and pathogenesis of individual glomerulonephritis is discussed. The following review is aimed to define current protocols of the recurrent primary glomerulonephritis therapy.
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Affiliation(s)
- Fedaey Abbas
- Department of Nephrology, Jaber El Ahmed Military Hospital, Safat 13005, Kuwait
- Faculty of Health and Science, University of Liverpool, Institute of Learning and Teaching, School of Medicine, Liverpool L69 3GB, United Kingdom
| | - Mohsen El Kossi
- Faculty of Health and Science, University of Liverpool, Institute of Learning and Teaching, School of Medicine, Liverpool L69 3GB, United Kingdom
- Doncaster Royal Infirmary, Doncaster DN2 5LT, United Kingdom
| | - Jon Kim Jin
- Faculty of Health and Science, University of Liverpool, Institute of Learning and Teaching, School of Medicine, Liverpool L69 3GB, United Kingdom
- Nottingham Children Hospital, Nottingham NG7 2UH, United Kingdom
| | - Ajay Sharma
- Faculty of Health and Science, University of Liverpool, Institute of Learning and Teaching, School of Medicine, Liverpool L69 3GB, United Kingdom
- Royal Liverpool University Hospitals, Liverpool L7 8XP, United Kingdom
| | - Ahmed Halawa
- Faculty of Health and Science, University of Liverpool, Institute of Learning and Teaching, School of Medicine, Liverpool L69 3GB, United Kingdom
- Department of Transplantation Surgery, Sheffield Teaching Hospitals, Sheffield S5 7AU, United Kingdom
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27
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Recurrent and de novo glomerulonephritis following renal transplantation: higher rates of rejection and lower graft survival. Int Urol Nephrol 2017; 49:2265-2272. [DOI: 10.1007/s11255-017-1719-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2017] [Accepted: 10/06/2017] [Indexed: 01/05/2023]
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28
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Kim Y, Yeo S, Kang S, Park W, Jin K, Park S, Park U, Kim H, Han S. Long-term Clinical Outcomes of First and Second Kidney Transplantation in Patients With Biopsy-Proven IgA Nephropathy. Transplant Proc 2017; 49:992-996. [DOI: 10.1016/j.transproceed.2017.03.063] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
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29
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Lionaki S, Panagiotellis K, Melexopoulou C, Boletis JN. The clinical course of IgA nephropathy after kidney transplantation and its management. Transplant Rev (Orlando) 2017; 31:106-114. [PMID: 28209246 DOI: 10.1016/j.trre.2017.01.005] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2016] [Revised: 12/07/2016] [Accepted: 01/26/2017] [Indexed: 01/06/2023]
Abstract
Immunoglobulin (Ig) A nephropathy is one of the most common primary glomerulonephritides worldwide causing end stage renal disease in up to 20-40% of affected patients, nearly two decades post diagnosis. Kidney transplantation is the treatment of choice for patients with renal failure, secondary to glomerular diseases. However, IgA nephropathy has a strong tendency to recur in the graft, and although initially thought to be a benign condition, several reports of graft loss, due to recurrent IgA nephropathy, there have been over the last three decades. Overall graft survival has been significantly improved in kidney transplantation, as a result of reduced incidence of acute rejection, as more potent and more specific immunosuppressive agents are now available in clinical practice. Thus, the rates of IgA nephropathy and other glomerulonephritides recurrence are expected to increase, since graft survival has been improved. However, the reported incidence of IgA nephropathy recurrence in the graft varies substantially across centers, as a consequence of different levels of interest, diverse biopsy policies and differing durations of follow up, of the published studies. Notably, recurrence rates of patients receiving graft biopsies by clinical indication only, ranges from 13% to 50% with graft loss being between 1.3% and 16%. The aim of this review is to underline important pathogenetic insights of IgA nephropathy, describe the clinical course of the disease after kidney transplantation, with emphasis on the incidence of recurrence and the associated risk factors, and finally provide all available options for its management in transplant recipients.
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Affiliation(s)
- Sophia Lionaki
- Department of Nephrology & Transplantation Unit, Laiko Hospital, National and Kapodistrian University of Athens, Faculty of Medicine, Athens, Greece.
| | - Konstantinos Panagiotellis
- Department of Nephrology & Transplantation Unit, Laiko Hospital, National and Kapodistrian University of Athens, Faculty of Medicine, Athens, Greece
| | - Christine Melexopoulou
- Department of Nephrology & Transplantation Unit, Laiko Hospital, National and Kapodistrian University of Athens, Faculty of Medicine, Athens, Greece
| | - John N Boletis
- Department of Nephrology & Transplantation Unit, Laiko Hospital, National and Kapodistrian University of Athens, Faculty of Medicine, Athens, Greece
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30
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Kennard AL, Jiang SH, Walters GD. Increased glomerulonephritis recurrence after living related donation. BMC Nephrol 2017; 18:25. [PMID: 28095803 PMCID: PMC5240239 DOI: 10.1186/s12882-016-0435-z] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2016] [Accepted: 12/28/2016] [Indexed: 11/29/2022] Open
Abstract
Background Kidney transplantation confers superior outcomes for patients with end stage kidney disease, and live donor kidneys associate with superior outcomes compared to deceased donor kidneys. Modern immunosuppression has improved rejection rates and transplant survival and, as a result, recurrence of glomerulonephritis has emerged as a major cause of allograft loss. However, many glomerulonephritides have significant genetic risk which may manifest through kidney intrinsic or systemic mechanisms. We hypothesise that heritable kidney intrinsic predisposition to glomerulonephritis will result in increased risk of glomerulonephritis recurrence in kidneys transplanted from genetically related donors. Methods We investigated the effect of living related donation on rates of recurrence and subsequent graft outcomes in 7236 patient from 28 years of ANZDATA transplant registry data. Data were analysed in R, using Kaplan Meier Survival analysis and adjusted analyses performed using Cox Proportional Hazards methods. A competing risk model was also analysed. Results Glomerulonephritis recurrence rates were significantly higher in living related donor grafts compared to either living unrelated or deceased donor grafts (p < 0 · 001). In IgA nephropathy, transplantation from living related donor kidneys demonstrated a 10 year recurrence rate of 16 · 7% compared to 7 · 1% in living unrelated donors and 9 · 2% in deceased donors (HR:1 · 7, 95% CI:1 · 26–2 · 26, p = 0 · 0005 for living related vs deceased donors). In focal segmental glomerulosclerosis, risk of recurrence at 10 years was 14 · 6% in living related donors compared to 10 · 8% in living unrelated donors and 6 · 6% in deceased donors (HR:2 · 2, 95% CI 1 · 34–3 · 64, p = 0 · 002) for living related vs deceased donors. Primary glomerulonephritis death censored graft survival was superior for living donor grafts, related or unrelated, compared to deceased donor grafts. Conclusions We identified a significant increase in the risk of glomerulonephritis recurrence in IgA Nephropathy and Focal Segmental Glomerulosclerosis in living related donors compared to a deceased donors.
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Affiliation(s)
- A L Kennard
- Department of Renal Medicine, The Canberra Hospital, PO Box 11, Woden, ACT, 2605, Australia
| | - S H Jiang
- Department of Renal Medicine, The Canberra Hospital, PO Box 11, Woden, ACT, 2605, Australia.,Department of Immunology and Infectious Diseases, John Curtin School of Medical Research, Australian National University, Canberra, Australia
| | - G D Walters
- Department of Renal Medicine, The Canberra Hospital, PO Box 11, Woden, ACT, 2605, Australia. .,Department of Immunology and Infectious Diseases, John Curtin School of Medical Research, Australian National University, Canberra, Australia. .,Australian National University Medical School, Garran, Australia. .,ANZDATA Registry, Adelaide 5000, Australia.
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Cosio FG, Cattran DC. Recent advances in our understanding of recurrent primary glomerulonephritis after kidney transplantation. Kidney Int 2016; 91:304-314. [PMID: 27837947 DOI: 10.1016/j.kint.2016.08.030] [Citation(s) in RCA: 116] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2016] [Revised: 08/09/2016] [Accepted: 08/11/2016] [Indexed: 02/06/2023]
Abstract
Recurrent glomerulonephritis (GN) is an important cause of kidney allograft failure, particularly in younger recipients. Approximately 15% of death-censored graft failures are due to recurrent GN, but this incidence is likely an underestimation of the magnitude of the problem. Overall, 18% to 22% of kidney allografts are lost due to GN, either recurrent or presumed de novo. The impact of recurrent GN on allograft survival was recognized from the earliest times in kidney transplantation. However, progress in this area has been slow, and our understanding of GN recurrence remains limited, in large part due to incomplete understanding of the pathogenesis of these diseases. This review focuses on recent advances in our general understanding of the pathophysiology of primary GN, the risk of recurrence in the allograft, and the consequences for kidney graft survival. We focus specifically on the most common forms of primary GN, including focal segmental glomerulosclerosis, membranous nephropathy, membranoproliferative glomerulonephritis, and IgA nephropathy. New understanding of the pathogenesis of these diseases has had direct clinical implications for transplantation, allowing better identification of candidates at high risk of recurrence and earlier diagnoses, and it is expected to lead to significance improvements in the therapy and perhaps even prevention of GN recurrence. More than ever, it is essential to fully characterize GN before transplantation as this information will direct our management posttransplantation. Further, the relative rarity of recurrent GN dictates the need for multicenter studies in order to evaluate, test, and validate recent advances and therapies.
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Affiliation(s)
- Fernando G Cosio
- Division of Nephrology and Hypertension, Department of Internal Medicine, William von Liebig Center for Transplantation and Clinical Regeneration Mayo Clinic, Rochester, Minnesota, USA.
| | - Daniel C Cattran
- Department of Nephrology, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada
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Nijim S, Vujjini V, Alasfar S, Luo X, Orandi B, Delp C, Desai N, Montgomery R, Lonze B, Alachkar N. Recurrent IgA Nephropathy After Kidney Transplantation. Transplant Proc 2016; 48:2689-2694. [DOI: 10.1016/j.transproceed.2016.08.011] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2016] [Accepted: 08/03/2016] [Indexed: 10/20/2022]
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A SPRY2 mutation leading to MAPK/ERK pathway inhibition is associated with an autosomal dominant form of IgA nephropathy. Eur J Hum Genet 2015; 23:1673-8. [PMID: 25782674 DOI: 10.1038/ejhg.2015.52] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2014] [Revised: 01/16/2015] [Accepted: 02/20/2015] [Indexed: 11/08/2022] Open
Abstract
IgA nephropathy (IgAN) represents the most common primary glomerulonephritis worldwide with a prevalence of 25-50% among patients with primary glomerulopathies. In ~5-10% of the patients the disease segregates with an autosomal dominant (AD) pattern. Association studies identified loci on chromosomes 1q32, 6p21, 8p23, 17p13, 22q12, whereas classical linkage studies on AD families identified loci on chromosomes 2q36, 4q26-31, 6q22, 17q12-22. We have studied a large Sicilian family where IgAN segregates with an AD transmission. To identify the causal gene, the exomes of two affected and one unaffected individual have been sequenced. From the bioinformatics analysis a p.(Arg119Trp) variant in the SPRY2 gene was identified as the probable disease-causing mutation. Moreover, functional characterization of this variant showed that it is responsible for the inhibition of the MAPK/ERK1/2 pathway. The same effect was observed in two sporadic IgAN patients carriers of wild-type SPRY2, suggesting that downregulation of the MAPK/ERK1/2 pathway represents a common mechanism leading to IgAN.
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Association Between Post-transplantation Immunoglobulin A Deposition and Reduced Allograft Function. Transplant Proc 2015; 47:332-6. [DOI: 10.1016/j.transproceed.2015.01.011] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2014] [Accepted: 01/14/2015] [Indexed: 12/14/2022]
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36
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Brenchley PE, Poulton K, Morton M, Picton ML. The genetic contribution to recurrent autoimmune nephritis. Transplant Rev (Orlando) 2014; 28:140-4. [DOI: 10.1016/j.trre.2014.01.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2013] [Accepted: 01/19/2014] [Indexed: 10/25/2022]
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Guo JQ, Song BL, Wu ZX, Wu WZ, Luo LT, Chen XW, He FQ, Zheng ZY, Yang SL, Tan JM. Prognostic factors for renal allograft survival in patients with immunoglobulin A nephropathy: a case control study. Mol Med Rep 2014; 9:1179-84. [PMID: 24535460 DOI: 10.3892/mmr.2014.1954] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2013] [Accepted: 01/31/2014] [Indexed: 11/06/2022] Open
Abstract
The renal allograft survival rates of patients with immunoglobulin A nephropathy (IgAN), and patients with or without other glomerular diseases, have yet to be fully elucidated. In this study, the clinicopathological factors associated with long-term allograft survival for the prognosis of renal allograft recipients with IgAN were examined. All patients enrolled in this study were diagnosed with IgAN following clinical and pathological examinations. Patients underwent renal graft biopsy and were hospitalized at the Fuzhou General Hospital between June, 2004 and December, 2010. Common demographic and clinical indicators were recorded in patients who had graft loss and in those who had functional renal grafts. Forty-two of the 202 biopsy specimens (20.8%) met the diagnostic criteria for IgAN and were divided into two groups, the graft loss group (n=17) and the functional graft group (n=25). Patients were followed up for 1-257 months after kidney transplantation. The mean patient age was 40.6 ± 9.3 years at the time of renal graft biopsy. Examination results indicated concomitant proteinuria and hematuria in 25 patients (59.5%) and proteinuria alone in six patients (14.3%). Graft loss occurred in 17 patients during the follow-up period. Comparison of the graft loss and the functional graft groups indicated that patients in the graft loss group were more likely to have proteinuria (P=0.047), high creatinine levels at the time of biopsy (P=0.009), low glomerular filtration rates (P=0.013), low serum total protein (P=0.01), a high Banff score (P=0.001), extensive glomerulosclerosis (P=0.002), a greater likelihood of crescent formation (P=0.01), severe tubular atrophy (P=0.013) and more extensive interstitial fibrosis (P=0.033). However, the two groups showed no significant differences in blood pressure, hematuria, BUN, UA, Hb, TG and CHO levels. The allograft survival rate of patients with IgAN was identified to be similar to that of patients with and without other glomerular diseases.
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Affiliation(s)
- Jun-Qi Guo
- Organ Transplant Institute, Fuzhou General Hospital, Fujian Medical University and Fujian Key Laboratory of Transplant Biology, Fuzhou, Fujian 350025, P.R. China
| | - Bao-Lin Song
- Department of Urology, Jiaxing Traditional Chinese Medical Hospital, Jiaxing, Zhejiang 314000, P.R. China
| | - Zhi-Xian Wu
- Organ Transplant Institute, Fuzhou General Hospital, Fujian Medical University and Fujian Key Laboratory of Transplant Biology, Fuzhou, Fujian 350025, P.R. China
| | - Wei-Zhen Wu
- Organ Transplant Institute, Fuzhou General Hospital, Fujian Medical University and Fujian Key Laboratory of Transplant Biology, Fuzhou, Fujian 350025, P.R. China
| | - Liu-Tao Luo
- Organ Transplant Institute, Fuzhou General Hospital, Fujian Medical University and Fujian Key Laboratory of Transplant Biology, Fuzhou, Fujian 350025, P.R. China
| | - Xiao-Wen Chen
- Organ Transplant Institute, Fuzhou General Hospital, Fujian Medical University and Fujian Key Laboratory of Transplant Biology, Fuzhou, Fujian 350025, P.R. China
| | - Fu-Qiang He
- Organ Transplant Institute, Fuzhou General Hospital, Fujian Medical University and Fujian Key Laboratory of Transplant Biology, Fuzhou, Fujian 350025, P.R. China
| | - Zhi-Yong Zheng
- Organ Transplant Institute, Fuzhou General Hospital, Fujian Medical University and Fujian Key Laboratory of Transplant Biology, Fuzhou, Fujian 350025, P.R. China
| | - Shun-Liang Yang
- Organ Transplant Institute, Fuzhou General Hospital, Fujian Medical University and Fujian Key Laboratory of Transplant Biology, Fuzhou, Fujian 350025, P.R. China
| | - Jian-Ming Tan
- Organ Transplant Institute, Fuzhou General Hospital, Fujian Medical University and Fujian Key Laboratory of Transplant Biology, Fuzhou, Fujian 350025, P.R. China
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Evaluation of tonsillectomy before kidney transplantation in patients with IgA nephropathy. Transpl Immunol 2013; 30:12-7. [PMID: 24246415 DOI: 10.1016/j.trim.2013.11.001] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2013] [Revised: 11/01/2013] [Accepted: 11/07/2013] [Indexed: 01/12/2023]
Abstract
The effectiveness of a tonsillectomy before kidney transplantation (KTx) in suppressing the recurrence of IgA nephropathy (IgAN) has never been studied. The aim of this study was to analyze the effectiveness of a preoperative tonsillectomy for preventing IgAN recurrence and to identify predictive risk factors for IgAN recurrence. Of the 462 recipients who underwent a KTx between 2006 and 2011, a total of 78 patients had biopsy-proven IgAN as their primary disease. Among these 78 patients, 28 patients (group 1) underwent a tonsillectomy and 50 patients (group 2) did not undergo a tonsillectomy before KTx. The time to recurrence was 15.5±8.7months, in group 1 and 20.2±18.6months in group 2. No significant difference was observed between the two groups (P=0.63). Using a multivariate Cox regression analysis, ABO incompatible KTx and acute rejection were associated with a lower incidence of recurrence (P=0.02 and 0.002 respectively). These results suggested that a preoperative tonsillectomy might not affect the recurrence of IgAN during a short-term follow-up period, whereas preoperative desensitization and the use of a higher steroid dose were effective for suppressing the recurrence of IgAN.
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Usefulness of Oxford classification in assessing immunoglobulin A nephropathy after transplantation. Transplantation 2013; 95:1491-7. [PMID: 23677050 DOI: 10.1097/tp.0b013e318291de65] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND We explored the efficacy of the Oxford classification for assessing native immunoglobulin A nephropathy (IgAN) in posttransplantation patients compared with the glomerular injury score and Haas classification. METHODS A total of 125 renal allograft biopsies obtained from 114 patients diagnosed with IgAN regardless of original disease were assessed. RESULTS The average time to biopsy was 70.5±45.3 months after transplantation. Glomeruli showed normal histology in 18.4%. Mesangial hypercellularity (M1), endocapillary hypercellularity (E1), segmental glomerulosclerosis (S1), and tubulointerstitial fibrosis (T1-2) were present in 12.8%, 6.4%, 45.6%, and 20.8% of the samples, respectively. There was a significant correlation between Oxford-MEST scores and glomerular injury score or Haas subclass. S1 and T1-2 were correlated with elevated serum creatinine level, proteinuria, and decreased estimated glomerular filtration rate, and E1 was correlated with decreased estimated glomerular filtration rate at the time of biopsy. The 10- and 15-year graft survival rates were 62.9% and 34.3%, respectively. The graft survival rate was significantly lower in the presence of S1 and T1-2. Endocapillary hypercellularity, segmental sclerosis, and tubulointerstitial fibrosis predicted graft survival and endocapillary hypercellularity and tubulointerstitial fibrosis also predicted serum creatinine doubling. CONCLUSIONS The Oxford classification scheme is useful for evaluating chronic graft dysfunction in patients with posttransplantation IgAN. In addition to tubulointerstitial fibrosis, the presence of endocapillary hypercellularity and segmental sclerosis should be included in the pathology report.
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Sprangers B, Kuypers DR. Recurrence of glomerulonephritis after renal transplantation. Transplant Rev (Orlando) 2013; 27:126-34. [PMID: 23954034 DOI: 10.1016/j.trre.2013.07.004] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2013] [Revised: 07/09/2013] [Accepted: 07/09/2013] [Indexed: 02/07/2023]
Abstract
Recurrence of glomerulonephritis following renal transplantation is considered an important cause of allograft failure. The incidence of recurrence of glomerulonephritis varies widely depending on the definition of recurrence (pathologic recurrence or clinicopathologic recurrence) and the original glomerular disease. Moreover the impact of recurrence of glomerular disease on allograft outcome varies widely between different forms of glomerulonephritis. Whereas IgA nephritis recurs in up to one third of transplanted patients, this is not associated with adverse effects on graft survival. In contrast, recurrent focal segmental glomerulosclerosis and membranoproliferative glomerulopathy have an unfavorable prognosis. Overall, long-term graft survival in patients transplanted for glomerulonephritis is comparable to survival in patients with other causes of ESRD. In recent years, several mechanisms for recurrent disease after transplantation (e.g. PLA2R antibodies in membranous nephropathy and suPAR in FSGS) have been identified, and these findings have helped to elucidate the pathogenesis of glomerular diseases. Although renal transplantation is the treatment of choice for end-stage renal disease as a consequence of glomerulonephritis, further studies are required to develop optimal strategies to prevent, diagnose and treat recurrent glomerular diseases.
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Affiliation(s)
- Ben Sprangers
- Department of Nephrology, University Hospitals Leuven, Leuven, Belgium
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41
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Australian registries—ANZDATA and ANZOD. Transplant Rev (Orlando) 2013; 27:46-9. [DOI: 10.1016/j.trre.2013.01.003] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2013] [Accepted: 01/22/2013] [Indexed: 11/18/2022]
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Sato K, Ishida H, Uchida K, Nitta K, Tanabe K. Risk Factors for Recurrence of Immunoglobulin A Nephropathy After Renal Transplantation: Single Center Study. Ther Apher Dial 2012; 17:213-20. [DOI: 10.1111/j.1744-9987.2012.01139.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Moroni G, Longhi S, Quaglini S, Gallelli B, Banfi G, Montagnino G, Messa P. The long-term outcome of renal transplantation of IgA nephropathy and the impact of recurrence on graft survival. Nephrol Dial Transplant 2012; 28:1305-14. [PMID: 23229925 DOI: 10.1093/ndt/gfs472] [Citation(s) in RCA: 82] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Few data are available on allograft survival at 15 years, the impact and the predictors of recurrence of the original disease in renal transplanted patients with IgA nephropathy (IgAN). METHODS In this retrospective study, we compared the long-term outcome of renal transplant in 190 patients with IgAN with that of 380 non-diabetic controls and evaluated the impact of recurrence of IgAN on the graft outcome. RESULTS At 15 years, the patient survival was 88.3% in IgAN patients and 82.6% in controls (P = 0.12), while the death-censored graft survival was 62.6 and 72.4%, respectively (P = 0.038). IgAN had a higher cumulative incidence of graft failures in comparison with controls even considering death as a competing risk (P = 0.025). At multivariate analysis, IgAN [relative risk (RR) = 1.468, P = 0.026], delayed graft function recovery (RR = 2.394, P = 0.000) and acute rejection (RR = 2.51, P = 0.000) were predictive of graft loss. IgAN recurred in 42 grafts (22.1%), of them, 12 were lost for recurrence and in another 6 recurrence was considered a concomitant cause of graft loss. The 15-year death censored graft survival was 68.3% in non-recurrent and 51.2% in recurrent patients (P = 0.069). Pure graft survival of non-recurrent IgAN patients was similar to that of controls (P = 0.406). At Cox analysis, the recurrence of IgAN significantly reduced from 1981 to 2010 (P = 0.0065, RR = 0.936). CONCLUSIONS IgAN emerged as an independent predictor of worse graft outcome in the long-term. Recurrence of IgAN seems to progressively reduce in transplants performed from 1981 to 2010.
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Affiliation(s)
- Gabriella Moroni
- Divisione di Nefrologia e Dialisi, Fondazione Ca' Granda Ospedale Maggiore Policlinico, Mangiagalli, Regina Elena IRCCS, Milano, Italy.
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Thiyagarajan UM, Bagul A, Frost J, Horsburgh T, Nicholson M. Role of Human Leukocyte Antigen, Donor-Specific Antibodies, and Their Impact in Renal Transplantation. Transplant Proc 2012; 44:1231-5. [DOI: 10.1016/j.transproceed.2011.10.054] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2011] [Accepted: 10/27/2011] [Indexed: 10/28/2022]
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45
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Kanaan N, Mourad G, Thervet E, Peeters P, Hourmant M, Vanrenterghem Y, De Meyer M, Mourad M, Maréchal C, Goffin E, Pirson Y. Recurrence and graft loss after kidney transplantation for henoch-schonlein purpura nephritis: a multicenter analysis. Clin J Am Soc Nephrol 2011; 6:1768-72. [PMID: 21734091 DOI: 10.2215/cjn.00520111] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND AND OBJECTIVES The actuarial risk at 5 years for clinical recurrence of Henoch-Schönlein purpura nephritis (HSPN) and graft loss caused by recurrence of -HSPN after renal transplantation was reported in 1994 to be as high as 35% and 11%, respectively. The aim of this study is to re-evaluate, in a large cohort of patients with a long-term follow-up, whether these rates have changed. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Patients from six transplant centers in Belgium and France with strict diagnostic criteria of HSPN and a potential post transplant follow-up of ≥3 years were included. RESULTS Forty-three patients were included. Patient survival is excellent: 98%, 95%, and 95% at 5, 10, and 15 years, respectively. Overall graft survival rates were 84%, 66%, and 56% at 5, 10, and 15 years, respectively. Clinical recurrence in a first kidney transplant occurred in five patients. Three patients lost their first graft due to HSPN recurrence 19 to 96 months after transplantation, two of whom had systemic signs of the illness. Actuarial risk for clinical recurrence in a first graft is 2.5% and 11.5% at 5 and 10 years, respectively. Actuarial risk for graft loss caused by recurrence in a first graft is 2.5% and 7.5% at 5 and 10 years, respectively. Severity of the disease at presentation and type of immunosuppression after transplantation did not affect recurrence. CONCLUSIONS We found that recurrence rates of HSPN after transplantation are lower than previously reported. The actuarial risk of graft loss from recurrence in a first graft is 7.5% at 10 years.
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Affiliation(s)
- Nada Kanaan
- Division of Nephrology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.
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Clayton P, McDonald S, Chadban S. Steroids and recurrent IgA nephropathy after kidney transplantation. Am J Transplant 2011; 11:1645-9. [PMID: 21797974 DOI: 10.1111/j.1600-6143.2011.03667.x] [Citation(s) in RCA: 74] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
We studied the impact of steroid use on kidney graft loss due to recurrent IgA nephropathy (IgAN). We used data from the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) to conduct a survival analysis of adult recipients of a first kidney transplant for IgAN who received a graft between 1988 and 2007. Predictors of graft loss due to recurrent IgAN were analyzed in a competing risk survival analysis with steroid use modeled as a time-varying covariate. Fifteen hundred twenty-one recipients with kidney failure due to biopsy-proven IgAN received a first kidney transplant during the study period. Four hundred and twenty-eight recipients experienced graft loss, of which 54 losses (12.6%) were attributed to recurrent IgAN. The overall 10-year cumulative incidence of graft loss from recurrent IgAN was 4.3% (95% CI 3.1-5.8). Prevalence of steroid use was 92% at baseline, 84% at 1 year and 64% at 5 years. After adjusting for age, sex, HLA mismatch, dialysis duration and transplant era, steroid use was strongly associated with a reduced risk of recurrence (subhazard ratio 0.50, 95% CI 0.30-0.84). These results suggest that the risk of graft loss from recurrent disease should be considered when tailoring immunosuppression for patients with IgAN.
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Affiliation(s)
- P Clayton
- Australia and New Zealand Dialysis and Transplant Registry, Royal Adelaide Hospital, Australia.
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Ponticelli C, Glassock RJ. Posttransplant recurrence of primary glomerulonephritis. Clin J Am Soc Nephrol 2010; 5:2363-72. [PMID: 21030574 DOI: 10.2215/cjn.06720810] [Citation(s) in RCA: 159] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
All forms of primary GN may recur after kidney transplantation and potentially jeopardize the survival of the graft. IgA nephritis (IgAN) may recur in approximately one third of patients, more frequently in younger patients and in those with a rapid progression of the original disease. However, with the exception of few patients with rapid progression, there is no evidence that recurrence of IgAN has a deleterious effect on graft survival at least up to 10 years. Recurrence of focal segmental glomerulosclerosis (FSGS) is often associated with nephrotic proteinuria and is more frequent in children, in patients with rapid progression of the original disease, and in those who lost a previous transplant from recurrence. The natural course of recurrent FSGS is usually unfavorable. Early and intensive plasmapheresis may obtain complete or partial response in several patients. Good results have also been reported with rituximab. Idiopathic membranous nephropathy (IMN) may recur in 30% to 40% of patients. The graft survival in patients with IMN is not different than that of patients with other renal diseases. Good results with rituximab have been reported. Membranoproliferative GN (MPGN) may recur in 27% to 65% of patients. The recurrence is more frequent and the prognosis is more severe in type II MPGN. Although recurrent GN is relatively frequent and may worsen the outcome of renal allografts in some patients, its effect is diluted by several other risk-factors that may have a greater effect than recurrent GN on the long-term graft survival.
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Han SS, Huh W, Park SK, Ahn C, Han JS, Kim S, Kim YS. Impact of recurrent disease and chronic allograft nephropathy on the long-term allograft outcome in patients with IgA nephropathy. Transpl Int 2009; 23:169-75. [PMID: 19761553 DOI: 10.1111/j.1432-2277.2009.00966.x] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
SUMMARY Although recurrent IgA nephropathy (IgAN) may lead to graft dysfunction after transplantation, donation from living related donor (LRD), with whom the risk of recurrence may be higher, is not a contraindication. Herein, we evaluated the natural history of allograft in recipients with IgAN and the risk factors influencing long-term allograft outcome. Recurrence rate and graft survival were assessed retrospectively in 221 IgAN patients, including transplants from 139 LRDs (62.9%). Ten-year cumulative rate for recurrent IgAN was 30.8%. The operation at younger age and donation from LRD were significant for the recurrence by multivariate analysis. Ten-year graft survival was affected by recurrent IgAN (61.0% in recurrent IgAN group vs. 85.1% in nonrecurrent, P < 0.01). However, transplants from LRDs did not show poor graft survival when compared with those from other types of donors. In transplants from LRDs, the incidence of chronic allograft nephropathy (CAN) was lower than those in grafts from deceased donors (10.8% vs. 19.5%, P < 0.05). When CAN was considered in addition to recurrence, the variance of graft survival was affected significantly by the development of CAN than by the recurrence. These results suggest that the detection and adequate management of CAN could improve graft outcome in transplant recipients with IgAN.
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Affiliation(s)
- Seung Seok Han
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
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Sakai K, Saneshige M, Takasu J, Yanagisawa T, Aoki Y, Kawamura T, Mizuiri S, Aikawa A. Clinical remission and pathological progression after tonsillectomy in a renal transplant patient with recurrent IgA nephropathy. Clin Transplant 2009; 23 Suppl 20:44-8. [DOI: 10.1111/j.1399-0012.2009.01009.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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