Long-Term Outcomes in IgA Nephropathy.
Across large registry and cohort studies, long-term outcomes in IgA nephropathy are generally poor, with most patients progressing to kidney failure within their lifetime, and time-averaged proteinuria, even at levels previously considered low risk, is the dominant predictor of progression.
Background
IgA nephropathy is the most common primary glomerulonephritis worldwide and follows a highly variable course, making early risk assessment important for management and for designing clinical trials. Long-term registry and cohort data have reshaped understanding of which patients are truly low risk, with particular focus on proteinuria thresholds and the rate of eGFR decline.
Study design
Evidence comes from large cohorts, including the UK RaDaR registry of 2299 adults and 140 children with biopsy-proven IgA nephropathy and proteinuria over 0.5 g/d or eGFR below 60, analysed using Kaplan-Meier and Cox regression with eGFR slope estimated via linear mixed models. Complementary data include a Chinese cohort of 2141 patients and other national registries with follow-up extending over many years.
Key findings
In the RaDaR cohort, median follow-up was 5.9 years, 50% of patients reached kidney failure or died, and median kidney survival was 11.4 years with a mean age at kidney failure or death of 48 years. Almost all patients were projected to reach kidney failure within their expected lifetime unless eGFR loss was held to 1 mL/min/1.73m2 per year or less. Time-averaged proteinuria was strongly associated with worse kidney survival; even patients with proteinuria below 0.88 g/g had substantial 10-year kidney failure rates, and each 10% reduction in time-averaged proteinuria carried a hazard ratio of 0.89 for kidney failure or death.
Clinical implications
These findings challenge the view that proteinuria below 1 g/d confers low risk, supporting more stringent proteinuria targets and closer monitoring even in apparently mild disease. The dominant prognostic role of time-averaged proteinuria reinforces sustained proteinuria reduction as a central treatment goal and as a surrogate endpoint in IgA nephropathy trials.
Category
Research
Source
Clin J Am Soc Nephrol
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