Long-term outcomes of IgA nephropathy in China

BACKGROUND: The long-term prognosis of immunoglobulin A nephropathy (IgAN) and the optimal target for proteinuria treatment remain controversial. This study, utilizing a large prospective cohort from China, aims to assess the long-term outcomes of IgAN and to explore the definition of proteinuria remission. METHODS: We enrolled 2141 patients with biopsy-proven IgAN, all with at least 12 months of follow-up, from a prospective IgAN cohort at Peking University First Hospital. We utilized Kaplan-Meier analysis, Cox regression and an estimated glomerular filtration rate (eGFR) slope calculated via a linear mixed model to investigate kidney outcomes. RESULTS: The median (Q1, Q3) baseline proteinuria was 1.26 (0.65, 2.40) g/day, and the eGFR was 80 (52, 103) mL/min/1.73 m2. After a mean follow-up of 5.8 (±4.4) years, 509 (24%) patients progressed to end-stage kidney disease (ESKD). The median kidney survival time was 12.4 years, the annual event rate of ESKD was 41.1 per 1000 person-years and the 15-year kidney survival rate was 40%. Time-averaged proteinuria level was strongly associated with kidney failure (adjusted hazard ratio 1.76, 95% confidence interval 1.65 to 1.88). Restriction cubic spline analysis indicated that the risk of ESKD increases rapidly when time-average proteinuria exceeded 0.5 g/day. There was no significant difference in long-term kidney survival between patients with proteinuria <0.3 g/day and those with 0.3-0.5 g/day, with both groups demonstrating a better prognosis. CONCLUSION: The long-term outcomes for patients with IgAN under current treatment strategies remain poor, with most progressing to ESKD within 15 years. Patients with time-averaged proteinuria ≥0.5 g/day experience worse kidney outcomes, challenging the previous view that proteinuria <1.0 g/day was associated with a low risk of kidney failure.