Quantifying association of early proteinuria and estimated glomerular filtration rate changes with long-term kidney failure in C3 glomerulopathy and immune-complex membranoproliferative glomerulonephritis using the United Kingdom RaDaR Registry
Sherry Masoud, Katie Wong, David Pitcher, Lewis Downward, Clare Proudfoot, Nicholas J.A. Webb, Sharirose Abat, Shazia Adalat, Joy Agbonmwandolor, Zubaidah Ahmad, Abdulfattah Alejmi, Rashid Almasarwah, Nicholas Annear, Mariana Araujo, Ellie Asgari, Amanda Ayers, Jyoti Baharani, Gowrie Balasubramaniam, Felix Jo-Bamba Kpodo, Lucy Bailey, Tarun Bansal, Alison Barratt, Jonathan Barratt, Megan Bates, Natalie Bayne, Janet Bendle, Sarah Benyon, Carsten Bergmann, Sunil Bhandari, Coralie Bingham, Preetham Boddana, Sally Bond, Fiona Braddon, Kate Bramham, Angela Branson, Stephen Brearey, Victoria Bridgett, Vicky Brocklebank, Sharanjit Budwal, Conor Byrne, Hugh Cairns, Brian Camilleri, Gary Campbell, Alys Capell, Margaret Carmody, Marion Carson, Tracy Cathcart, Christine Catley, Karine Cesar, Melanie Chan, Houda Chea, James Chess, Chee Kay Cheung, Katy-Jane Chick, Nihil Chitalia, Martin Christian, Tina Chrysochou, Katherine Clark, Christopher Clayton, Rhian Clissold, Helen Cockerill, Joshua Coelho, Elizabeth Colby, Viv Colclough, Eileen Conway, H. Terence Cook, Wendy Cook, Theresa Cooper, Richard J. Coward, Sarah Crosbie, Gabor Cserep, Anjali Date, Katherine Davidson, Amanda Davies, Neeraj Dhaun, Ajay Dhaygude, Lynn Diskin, Abhijit Dixit, Eunice Ann Doctolero, Suzannah Dorey, Lewis Downard, Mark Drayson, Gavin Dreyer, Tina Dutt, Kufreabasi Etuk, Dawn Evans, Jenny Finch, Frances Flinter, James Fotheringham, Lucy Francis, Daniel P. Gale, Daniel P. Gale, Hugh Gallagher, David Game, Eva Lozano Garcia, Madita Gavrila, Susie Gear, Colin Geddes, Mark Gilchrist, Matt Gittus
Abstract
INTRODUCTION: C3 glomerulopathy (C3G) and immune-complex membranoproliferative glomerulonephritis (IC-MPGN) are rare disorders that frequently result in kidney failure over the long-term. Presently, 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 estimated glomerular filtration rate (eGFR) and proteinuria predict the clinically important outcome of kidney failure. METHODS: We address this using longitudinal data from the UK Registry of Rare Kidney Diseases (RaDaR) involving retrospective and prospective data collection with linkage to hospital laboratories via automated feeds of 371 patients. Analyses of kidney survival were conducted using Kaplan-Meier and Cox regression with eGFR slope estimated using linear mixed models. RESULTS: In a median of 11.0 (inter quartile range 7.4-15.1) years follow-up, 148 patients (40%) reached kidney failure. There was no significant difference in progression to kidney failure between C3G and IC-MPGN groups. Baseline urine protein-creatinine ratio (UPCR), although high, was not associated with kidney failure in either group. Two-year eGFR slope had a modest association with kidney failure. In contrast, both 20%‒50% and 50 mg/mmol reductions in UPCR between 0-12 months were associated with lower kidney failure risk in both groups. Notably, those with a UPCR under 100 mg/mmol at 12 months had a substantially lower risk of kidney failure (hazard ratio 0.10 (95% confidence interval 0.03-0.30). CONCLUSIONS: Overall, proteinuria a short time after diagnosis is strongly associated with long-term outcomes and a UPCR under 100 mg/mmol at one year is associated with a substantially lower kidney failure risk.