Primary IgA nephropathy is the most common type of glomerulonephritis and a major cause of chronic kidney disease and kidney failure worldwide. Current understanding of the risk of progression has been based on data from short-term trials, highlighting the need for surrogate endpoints that can predict long-term outcomes. Regulatory authorities have accepted reduction in proteinuria as an appropriate surrogate endpoint for IgA nephropathy trials, but questions still remain.

To better understand long-term IgA nephropathy outcomes in patients traditionally considered low risk for kidney failure, data from the UK National Registry of Rare Kidney Diseases, RaDaR, were retrospectively analyzed. Patient eligibility included biopsy-proven primary IgA nephropathy and proteinuria above 0.5 g/day or estimated glomerular filtration rate – eGFR – below 60 mL/min/1.73 m². In total, 2,439 patients were analyzed.

Outcomes in this large cohort of patients were generally poor. The median follow-up was 5.9 years, during which 50% of patients reached kidney failure or died. Findings demonstrated a significant association between persistent proteinuria and rapid loss of eGFR and worse kidney survival. Higher time-averaged levels of proteinuria were significantly associated with more rapid progression to kidney failure or death. Across all proteinuria levels, patients with IgA nephropathy, including those traditionally considered “low risk”, were at risk of developing kidney failure within 10 years. Analyses also showed that patients with a more rapid eGFR loss had a lower 5-year kidney survival rate.

The poor outcomes observed in the RaDaR registry highlighted the need to re-evaluate the current approach to patient care in IgA nephropathy, particularly the need to target a lower threshold of proteinuria, consider combination therapies, and implement a lower threshold for biopsy.