CKD progression, kidney failure, and mortality among US patients with IgA nephropathy.

Background and hypothesis: We assessed disease progression among patients with immunoglobulin A nephropathy (IgAN) and characterized factors associated with risk for adverse outcomes.

Methods: A retrospective longitudinal cohort (2000-2022) study of adults with biopsy-confirmed IgAN within Kaiser Permanente Southern California was performed. The outcome of interest was a composite of ≥50% estimated glomerular filtration rate (eGFR) decline, kidney failure, or mortality. Cox proportional hazards regression modeling was used to estimate hazard ratios (HR) for the eGFR decline/kidney failure with adjustment for potential confounders.

Results: Among 655 patients with primary IgAN (31% Asian/Pacific Islander, 3% Black, 40% Hispanic/Latino, 24% White), 234 (36%) reached the composite outcome of ≥50% eGFR decline (17%), kidney failure (16%), or mortality (3%). The composite outcome occurred at a rate of 79.4 events (95%CI 69.6, 90.7) per 1000 patient-years, with a median time to event of 2.7 years. Compared to urine protein creatinine ratio (UPCR) <0.5 g/g vs 0.5 - <1 g/g, 1 - 2 g/g, and >2 g/g, the HR (95% CI) for ≥50% eGFR decline/kidney failure were 2.4 (1.1, 5.1), 3.2 (1.5, 6.6), and 5.1 (2.5, 10.4) for baseline UPCR and 5.4 (2.3, 13.0), 14.4 (16.5, 32.2), and 41.2 (17.9, 94.5) for time averaged UPCR. Lower baseline eGFR and diabetes were also associated with higher risk, while age ≥30 years was associated with lower risk for ≥50% eGFR decline/kidney failure. There were no clear trends differentiating risk by race/ethnicity.

Conclusion: In this large, diverse cohort, high rates of kidney outcomes occurred within a relatively short follow-up duration. Our findings suggest that IgAN carries elevated risk for kidney outcomes starting at proteinuria levels ≥0.5 g/g, in contrast to earlier perceptions that levels below 1 g/g are associated with low risk.