Association of Histologic Parameters with Outcome in C3 Glomerulopathy and Idiopathic Immunoglobulin-Associated Membranoproliferative Glomerulonephritis

Abstract

Background and objectivesC3 glomerulopathy and idiopathic Ig-associated membranoproliferative GN are kidney diseases characterized by abnormal glomerular complement C3 deposition. These conditions are heterogeneous in outcome, but approximately 50% of patients develop kidney failure within 10 years.Design, setting, participants, & measurementsTo improve identification of patients with poor prognosis, we performed a detailed analysis of percutaneous kidney biopsies in a large cohort of patients. Using a validated histologic scoring system, we analyzed 156 native diagnostic kidney biopsies from a retrospective cohort of 123 patients with C3 glomerulopathy and 33 patients with Ig-associated membranoproliferative GN. We used linear regression, survival analysis, and Cox proportional hazards models to assess the relationship between histologic and clinical parameters with outcome.ResultsFrequent biopsy features were mesangial expansion and hypercellularity, glomerular basement membrane double contours, and endocapillary hypercellularity. Multivariable analysis showed negative associations between eGFR and crescents, interstitial inflammation, and interstitial fibrosis/tubular atrophy. Proteinuria positively associated with endocapillary hypercellularity and glomerular basement membrane double contours. Analysis of second native biopsies did not demonstrate associations between immunosuppression treatment and improvement in histology. Using a composite outcome, risk of progression to kidney failure associated with eGFR and proteinuria at the time of biopsy, cellular/fibrocellular crescents, segmental sclerosis, and interstitial fibrosis/tubular atrophy scores.ConclusionsOur detailed assessment of kidney biopsy data indicated that cellular/fibrocellular crescents and interstitial fibrosis/tubular atrophy scores were significant determinants of deterioration in kidney function.

Kidney diseases

“…Recently, it has been shown that in three of 11 individuals initially diagnosed with IC‐MPGN, the diagnosis changed to C3GN following a second biopsy. 108 These findings are consistent with the hypothesis that during the course of C3G, there may be episodes of IC deposition, possibly triggered by infections.…”

“…This likely relates to IC induced by infections or other triggers that initiate the disease in patients who have an underlying AP abnormality, and C3‐dominance may become evident following classical pathway inactivation after the resolution of infection or after immunosuppressive therapy. Recently, it has been shown that in three of 11 individuals initially diagnosed with IC‐MPGN, the diagnosis changed to C3GN following a second biopsy 108 . These findings are consistent with the hypothesis that during the course of C3G, there may be episodes of IC deposition, possibly triggered by infections.…”

“…Relevant prognostic factors, reported in both adults and children, include NS at onset and a higher proportion of sclerotic glomeruli and crescents in kidney biopsies 119 . The predictive value of the histological features regarding disease outcome has recently been documented 108 . In a large cohort of C3G and IC‐MPGN patients, the risk of progression to kidney failure was associated with estimated glomerular filtration rate (GFR) and proteinuria at the time of biopsy, cellular/fibrocellular crescents, segmental sclerosis, and interstitial fibrosis/tubular atrophy scores.…”

Prognostication for C3 Glomerulopathy and Idiopathic Immunoglobulin-Associated Membranoproliferative Glomerulonephritis

“…Our group has recently proposed a simple and easy to use nomogram to predict the risk of kidney failure in C3 glomerulopathy (8) on the basis of the eGFR, proteinuria, and total chronicity score at baseline, although these results have not yet been validated in independent cohorts. The study by Lomax-Browne et al (6) is undoubtedly one of the most important cohorts published to date and sheds light on the main histologic determinants of outcomes in C3 glomerulopathy/Ig-mediated MPGN. Their main strengths are the large number of patients included from different countries, the inclusion of well-characterized idiopathic Ig-MPGN, and most importantly, the centralized review of all kidney biopsies.…”

“…have not yet been validated in independent cohorts. The study by Lomax-Browne et al (6) is undoubtedly one of the most important cohorts published to date and sheds light on the main histologic determinants of outcomes in C3 glomerulopathy/Ig-mediated MPGN. Their main strengths are the large number of patients included from different countries, the inclusion of well-characterized idiopathic Ig-MPGN, and most importantly, the centralized review of all kidney biopsies.…”