Quantifying association of early proteinuria and eGFR changes with long-term kidney failure hazard in C3G and IC-MPGN

Abstract

AbstractBackgroundC3 glomerulopathy (C3G) and immune-complex membranoproliferative glomerulonephritis (IC-MPGN) are rare disorders that frequently result in kidney failure over the long-term. At present, there are no disease-specific treatments approved for these disorders, although there is much interest in the therapeutic potential of complement inhibition. However, the limited duration and necessarily small size of controlled trials means there is a need to quantify how well short-term changes in eGFR and proteinuria predict the clinically important outcome of kidney failure. We aimed to address this using longitudinal data from the UK National Registry of Rare Kidney Diseases (RaDaR).MethodsRaDaR involves both retrospective and prospective data collection with linkage to hospital laboratories via automated feeds. 667 patients were included. Analyses of kidney survival were conducted using Kaplan–Meier and Cox regression. eGFR slope was estimated using linear mixed models.ResultsOver a median of 10.1 (IQR 6.9-14.3) years follow-up, 253/667 (38%) reached kidney failure. There was no difference in progression to kidney failure between C3G, IC-MPGN and Primary MPGN Not Otherwise Specified subgroups (p=0.75). Baseline urine protein creatinine ratio (UPCR), although high, was not associated with kidney failure risk. 2-year eGFR slope had a modest effect on kidney failure risk. In contrast, both 20-50% and 0.44g/g (50mg/mmol) reductions in time-averaged UPCR at 12 months were strongly associated with lower kidney failure risk (p≤0.002). Most notably, those with a UPCR <0.88g/g (<100mg/mmol) at 12 months had a substantially lower risk of kidney failure (HR 0.15 (95%CI 0.05-0.41).ConclusionsWe quantified the relationships between early changes in both eGFR and proteinuria with long-term kidney survival. We demonstrate that proteinuria a short time after diagnosis is a strong predictor of long-term outcome and that a UPCR <0.88g/g (<100mg/mmol) at 1 year is associated with a substantially lower kidney failure risk.