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. 2025 Oct 30;40(11):2104-2117.
doi: 10.1093/ndt/gfaf084.

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

John J Sim  1   2   3 , Qiaoling Chen  2 , Nancy Cannizzaro  2 , Ancilla W Fernandes  4 , Cibele Pinto  4 , Simran K Bhandari  3   5 , John Chang  2 , Asher D Schachter  6 , Mohit Mathur  6
Affiliations

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

John J Sim et al. Nephrol Dial Transplant. .

Abstract

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.

Keywords: IgAN; epidemiology; immunoglobulin A nephropathy; kidney failure.

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Conflict of interest statement

John J. Sim currently has or has had research grant support from Otsuka Pharmaceutical Development and Commercialization, Vera Pharmaceuticals, NIH/Kidney Nutrition Obesity and Diabetes Study Section (co-investigator, Manjula Kurella Tamura PI), and Kaiser Permanente Southern California Clinician Investigator award. Ancilla W. Fernandes and Cibele Pinto are employees of Otsuka. Asher D. Schachter and Mohit Mathur are employees of Visterra, Inc. None of the other authors have any disclosures to report.

Figures

Graphical Abstract
Graphical Abstract
Figure 1:
Figure 1:
Study population.
Figure 2:
Figure 2:
Flow diagram (Alluvial plot) of changes in UPCR at baseline and during follow up.
Figure 3:
Figure 3:
(a) Cumulative incidence (incidence risk) of the composite outcome by baseline UPCR. (b) Cumulative incidence (incidence risk) of the composite outcome with time-averaged UPCR values.
See this image and copyright information in PMC

References

    1. Lai KN, Tang SC, Schena FP et al. IgA nephropathy. Nat Rev Dis Primers 2016;2:16001. 10.1038/nrdp.2016.1 - DOI - PubMed
    1. McGrogan A, Franssen CF, de Vries CS. The incidence of primary glomerulonephritis worldwide: a systematic review of the literature. Nephrol Dial Transplant 2011;26:414–30. 10.1093/ndt/gfq665 - DOI - PubMed
    1. Kiryluk K, Freedberg DE, Radhakrishnan J et al. Global Incidence of IgA nephropathy by race and ethnicity: a systematic review. Kidney360 2023;4:1112–22. - PMC - PubMed
    1. Sim JJ, Chen Q, Cannizzaro N et al. Incidence of adult primary immunoglobulin A nephropathy among a racially/ethnically diverse population in the United States. Am J Nephrol 2024;56:172–7. 10.1159/000541869 - DOI - PMC - PubMed
    1. Coppo R, Lofaro D, Camilla RR et al. Risk factors for progression in children and young adults with IgA nephropathy: an analysis of 261 cases from the VALIGA European cohort. Pediatr Nephrol 2017;32:139–50. 10.1007/s00467-016-3469-3 - DOI - PubMed

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