Recurrence of FSGS after Kidney Transplantation in Adults

Abstract

Background and objectivesFSGS 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, & measurementsThe 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.ResultsAmong 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.ConclusionsIdiopathic 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.

Autoimmunity in Focal Segmental Glomerulosclerosis: A Long-Standing Yet Elusive Association

“…Cases of FSGS associated with severe tubulointerstitial lesions were also reported in patients taking cocaine, heroin, calcineurin inhibitors, or lithium (14)(15)(16). Podocytopathies with an FSGS pattern can be also caused by HIV, SARS-CoV-2, Parvovirus B19, cytomegalovirus methods in treating this condition (22)(23)(24), and by disease resolution after graft re-transplantation from a patient with FSGS recurrence to a diabetic recipient (25). Consistently, exposure to serum from patients with post-transplant recurrence was shown to increase glomerular permeability both in vitro and in animal models (26,27).…”

“…After renal transplantation, primary FSGS has a high rate of recurrence in the allograft, which significantly reduces longterm graft survival (118). There is considerable variability among case series, but recent data from pediatric and adult cohorts indicate that the overall recurrence rate is similar across age groups, affecting approximately one third of patients (23,119). These reports may however underestimate the true incidence of primary FSGS recurrence, because most studies defined primary forms irrespective of the presence of nephrotic syndrome or the degree of foot process effacement on EM, likely including secondary FSGS forms in the analysis.…”

Whole-Exome Sequencing Solved over 2-Decade Kidney Disease Enigma

“…Interestingly, his son, who also harbored the same mutation, presented with steroid-resistant nephrotic syndrome with pathologic findings of FSGS pattern at early age. As genetic FSGS had a very low recurrence rate in transplanted kidney and primary FSGS had about 30% rate of recurrence after kidney transplantation [2, 3], patient J had posttransplant de novo membranous nephropathy in the transplanted kidney together with LMX1B-associated nephropathy in the native kidney.…”

Recurrencia de enfermedades glomerulares en trasplante renal

“…Pautas similares se establecen en los trasplantes con GN membranosa donde gracias al nivel de anti-PLA2R, al uso de rituximab, e incluso bortezomib, se han tenido casos con buena respuesta. 5,9 En este contexto el manejo postrasplante renal es esencial. La disfunción renal, proteinuria incluso menor de 300 mg en 24 horas y hematuria macro o microscópica en dos o más determinaciones con sonograma renal en límites, sin obstrucción y resto de estudios de laboratorio sin datos anormales deben ser indicación de biopsia renal y en caso de biopsia protocolizada, la detección de lesiones glomerulares recurrentes es de mayor utilidad clínica y terapéutica, pues nos permite un tratamiento más temprano.…”