Remission of steroid-resistant nephrotic syndrome due to focal and segmental glomerulosclerosis using rituximab

BACKGROUND: Therapeutic options are limited in cases of focal and segmental glomerulosclerosis (FSGS) that fail to respond to steroids and calcineurin inhibitors. We describe a case in which steroid-resistant nephrotic syndrome (SRNS) secondary to FSGS did not respond to conventional treatment, but was successfully treated with rituximab. Unlike previous reports in which rituximab was used in conjunction with a calcineurin inhibitor, we present the first case where rituximab was used as the sole therapeutic agent. CASE REPORT: An 11-month-old boy presented with severe manifestations of primary nephrotic syndrome with a subsequent non-responsive steroid course. A renal biopsy confirmed FSGS, with normal staining for podocin and nephrin. Genetic studies for podocin were normal. The child developed ciclosporin-induced hemolytic uremic syndrome (HUS), and the response to plasma exchange, following ciclosporin withdrawal, was only temporary. A trial of a combination of mycophenolate and dexamethasone did not have any effect on proteinuria or fluid status. Four weekly rituximab infusions at 375 mg/m(2)/dose induced a complete remission without any adverse effects. CONCLUSIONS: This case suggests that rituximab may be used as the sole therapeutic agent in the treatment of SRNS secondary to FSGS, especially in cases where calcineurin inhibitors are contraindicated.     

MCP1 2518 A/G polymorphism affects progression of childhood focal segmental glomerulosclerosis

Abstract

Monocyte chemoattractant protein-1 (MCP-1) is a highly specific chemokine for monocytes and plays roles in pathogenesis of various renal diseases. The aim of this study is to investigate the effect of MCP1 2518 A/G polymorphism on the incidence and clinical course of focal segmental glomerulosclerosis (FSGS) in children. MCP1 2518 A/G genotype was identified by PCR-RFLP in 60 biopsy-proven FSGS patients, 76 steroid sensitive nephrotic syndrome (SSNS) patients, and 96 healthy children. MCP-1 levels in urine and serum were measured by ELISA in all patients and the correlations of genotype with MCP-1 levels and clinical outcome were evaluated. The genotype frequencies for MCP1 were similar in all groups. The percentage of patients who develop chronic renal failure was higher in patients with AA allele compared to GA or GG alleles (46% vs. 35% respectively, p?<?0.01, Odds ratio: 1.59). Serum MCP-1 levels were similar in all groups, whereas urinary MCP-1 levels of the patients with FSGS (1680?pg/mg creatinine) were significantly higher than that of patients with SSNS (365?pg/mg creatinine, p?<?0.05) and healthy controls (348?pg/mg creatinine; p?<?0.05). Urinary MCP-1 levels were correlated with the degree of proteinuria in FSGS group (r?=?0.529, p?=?0.016). Our results suggest that the AA genotype might be a risk factor for the progression of renal disease in FSGS and MCP1 genotyping may help the physicians to predict prognosis in these patients.     

A Form of Apolipoprotein A‐I Is Found Specifically in Relapses of Focal Segmental Glomerulosclerosis Following Transplantation

Recurrence of idiopathic focal segmental glomerulosclerosis (FSGS) following kidney transplantation occurs in a large percentage of patients. Accurate prediction of recurrence and elucidation of its pathogenesis are major therapeutic goals. To detect differential proteins related to FSGS recurrence, proteomic analysis was performed on plasma and urine samples from 35 transplanted idiopathic FSGS patients, divided into relapsing and nonrelapsing. Several proteins were detected increased in urine of relapsing FSGS patients, including a high molecular weight form of apolipoprotein A‐I, named ApoA‐Ib, found exclusively in relapsing patients. This finding was verified by Western blot individually in the 35 patients and validated in an independent group of 40 patients with relapsing or nonrelapsing FSGS, plus two additional groups: FSGS‐unrelated patients showing different proteinuria levels (n = 30), and familial FSGS transplanted patients (n = 14). In the total of 119 patients studied, the ApoA‐Ib form was detected in 13 of the 14 relapsing FSGS patients, and in one of the 61 nonrelapsing patients. Only one of the 30 patients with FSGS‐unrelated proteinuria tested positive for ApoA‐Ib, and was not detected in familial patients. Urinary ApoA‐Ib is associated with relapses in idiopathic FSGS and warrants additional investigation to determine its usefulness as biomarker of relapse following transplantation.     

Renal transplant outcomes in primary FSGS compared with other recipients and risk factors for recurrence: A national review of the Irish Transplant Registry

Introduction

Primary focal segmental glomerular sclerosis (p‐FSGS) is commonly complicated by recurrence (r‐FSGS) post‐transplantation. Our objective was to describe Irish outcomes for transplantation after end‐stage renal disease (ESRD) due to p‐FSGS, specifically rates of, and treatments for, r‐FSGS.

Patients and Methods

Irish patients with biopsy‐proven FSGS were identified from the Irish National Kidney Transplant database (1982‐2015). Medical record review was performed to identify predictors of r‐FSGS and treatments for r‐FSGS. Transplant outcomes were compared to outcomes in all renal transplants performed during the same time period using registry data. Demographic and clinical predictors of r‐FSGS were identified. Statistical analysis was performed using Stata (version 13, College Station, TX, USA).

Results

Thirty‐eight transplant recipients had biopsy‐proven p‐FSGS, 16 received a second transplant. A total of 3846 transplants formed the comparator group. r‐FSGS complicated 60.5% (23/38) of first transplants. Eighty‐six percent (10/12) of patients with previous r‐FSGS developed recurrent disease after further transplantation. Patients with p‐FSGS receiving a first renal transplant had higher rate of graft failure than those with another cause of ESRD (HR 1.9, 95% CI 1.152‐3.139). Sixteen patients received immunotherapy for r‐FSGS; 12 (86%) had at least partial response, but two (14%) developed significant complications.

Discussion

We demonstrate high rates of r‐FSGS and describe modest success from with treatments for r‐FSGS.