Dataset Information

Recurrence of FSGS after Kidney Transplantation in Adults.

ABSTRACT:

Background and objectives

FSGS recurrence after kidney transplantation is a major risk factor for graft loss. However, the natural history, clinical predictors, and response to treatment remain unclear because of small sample sizes and poor generalizability of single-center studies, and disease misclassification in registry-based studies. We therefore aimed to determine the incidence, predictors, and treatment response of recurrent FSGS in a large cohort of kidney transplant recipients.

Design, setting, participants, & measurements

The Post-Transplant Glomerular Disease (TANGO) project is an observational, multicenter, international cohort study that aims to investigate glomerular disease recurrence post-transplantation. Transplant recipients were screened for the diagnosis of idiopathic FSGS between 2005 and 2015 and details were recorded about the transplant, clinical outcomes, treatments, and other risk factors.

Results

Among 11,742 kidney transplant recipients screened for FSGS, 176 had a diagnosis of idiopathic FSGS and were included. FSGS recurred in 57 patients (32%; 95% confidence interval [95% CI], 25% to 39%) and 39% of them lost their graft over a median of 5 (interquartile range, 3.0-8.1) years. Multivariable Cox regression revealed a higher risk for recurrence with older age at native kidney disease onset (hazard ratio [HR], 1.37 per decade; 95% CI, 1.09 to 1.56). Other predictors were white race (HR, 2.14; 95% CI, 1.08 to 4.22), body mass index at transplant (HR, 0.89 per kg/m²; 95% CI, 0.83 to 0.95), and native kidney nephrectomies (HR, 2.76; 95% CI, 1.16 to 6.57). Plasmapheresis and rituximab were the most frequent treatments (81%). Partial or complete remission occurred in 57% of patients and was associated with better graft survival.

Conclusions

Idiopathic FSGS recurs post-transplant in one third of cases and is associated with a five-fold higher risk of graft loss. Response to treatment is associated with significantly better outcomes but is achieved in only half of the cases.

SUBMITTER: Uffing A

PROVIDER: S-EPMC7015092 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Recurrence of FSGS after Kidney Transplantation in Adults.

Uffing Audrey A Pérez-Sáez Maria José MJ Mazzali Marilda M Manfro Roberto C RC Bauer Andrea Carla AC de Sottomaior Drumond Frederico F O'Shaughnessy Michelle M MM Cheng Xingxing S XS Chin Kuo-Kai KK Ventura Carlucci G CG Agena Fabiana F David-Neto Elias E Mansur Juliana B JB Kirsztajn Gianna Mastroianni GM Tedesco-Silva Helio H Neto Gilberto M V GMV Arias-Cabrales Carlos C Buxeda Anna A Bugnazet Mathilde M Jouve Thomas T Malvezzi Paolo P Akalin Enver E Alani Omar O Agrawal Nikhil N La Manna Gaetano G Comai Giorgia G Bini Claudia C Muhsin Saif A SA Riella Miguel Carlos MC Hokazono Silvia R SR Farouk Samira S SS Haverly Meredith M Mothi Suraj Sarvode SS Berger Stefan P SP Cravedi Paolo P Riella Leonardo V LV

Clinical journal of the American Society of Nephrology : CJASN 20200123 2

<h4>Background and objectives</h4>FSGS recurrence after kidney transplantation is a major risk factor for graft loss. However, the natural history, clinical predictors, and response to treatment remain unclear because of small sample sizes and poor generalizability of single-center studies, and disease misclassification in registry-based studies. We therefore aimed to determine the incidence, predictors, and treatment response of recurrent FSGS in a large cohort of kidney transplant recipients.< ...[more]

PMID: 31974287

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Project description:Recurrence of focal segmental glomerulosclerosis (rFSGS) after kidney transplantation is a cause of early and accelerated graft loss. Immuneadsorption can alleviate renal dysfunction and suggests that circulating antibodies (Ab) are likely implicated in disease pathogenesis. To evaluate pathogenic Ab in rFSGS, we processed 141 unique serum samples from patients with and without primary rFSGS (n=64) and 34 non-FSGS control, transplanted at five (US and EU) hospitals. 9000 antigens were screened in pre-transplant sera by protein arrays and 10 Ab targeting glomerular antigens were selected for ELISA validation. A panel of 7 Ab (CD40, PTPRO, CGB-5, FAS, P2RY11, SNRPB2 and APOL2) could predict post-transplant FSGS recurrence with 92% accuracy. Pre-transplant elevation of anti-CD40 Ab levels alone had a substantial impact (78% accuracy) on the identification of rFSGS risk after transplantation. Epitope mapping of CD40 with customized peptide arrays and rFSGS sera demonstrated altered immunogenicity of the extracellular CD40 domain in rFSGS. Immunohistochemistry of CD40 demonstrated a differential expression of these antigens in FSGS compared to non-FSGS. Anti-CD40 Ab purified from rFSGS patients were uniquely pathogenic in human podocyte cultures; injection of these Ab resulted in heightened proteinuria, independently and in combination with suPAR in a rodent model, abrogated by injection of monoclonal Ab to CD40. In conclusion, a panel of 7 Ab can identify primary FSGS patients at high risk of recurrence prior to transplantation, allowing for customized therapies and improved patient selection for transplant. Intra-renal CD40 is an important axis of disease pathogenesis, and human trials of anti-CD40 therapies are warranted to evaluate their efficacy in preventing rFSGS and improving graft survival. The purpose of the study was to identify potential auto-Abs associated with rFSGS. We used a discovery set of pre-transplant sera from 20 unique patients with biopsy confirmed diagnosis of primary FSGS as their cause of ESRD, of which 10 had progressed to rFSGS within the first post-transplant year and 10 did not have recurrence of proteinuria or histological disease after transplantation (nrFSGS).

Dataset Information

Recurrence of FSGS after Kidney Transplantation in Adults.

Background and objectives

Design, setting, participants, & measurements

Results

Conclusions

Publications

Recurrence of FSGS after Kidney Transplantation in Adults.

Similar Datasets

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