Long-term outcomes of IgA nephropathy in China.

Background and hypothesis: The long-term prognosis of IgA 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 2 141 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 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/d, and the estimated GFR was 80 (52, 103) mL/min/1.73m2. 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 HR: 1.76, 95%CI: 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/d. There was no significant difference in long-term kidney survival between patients with proteinuria < 0.3 g/d and those with 0.3-0.5 g/d, 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/d experience worse kidney outcomes, challenging the previous view that proteinuria < 1.0 g/d was associated with a low risk of kidney failure.