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

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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% confidence intervals (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 vs 0.5-<1 g/g, 1-2, 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.

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