Annual eGFR slope and Adverse kidney outcome in IgA nephropathy: A post-hoc analysis of the Japan IgA Nephropathy Cohort Study (J-IGACS)
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Background
In IgA nephropathy (IgAN), early surrogate markers that reflect disease progression are critical for understanding long-term outcomes. While prior studies have suggested a potential role for eGFR slope, its validity as a surrogate endpoint requires further validation. We here investigated the association between longitudinal changes in eGFR and kidney outcomes in a large Japanese IgAN cohort.
Methods
Patients with biopsy-confirmed IgAN enrolled in the Japan IgA Nephropathy Cohort Study (J-IGACS) were analyzed. Individual eGFR slopes were estimated using a linear mixed-effects model. The association between eGFR slope and a composite kidney outcome, defined as a ≥40 decline in eGFR or the initiation of kidney replacement therapy, was assessed using joint modeling of longitudinal and survival data, adjusting for key clinical and histopathological covariates.
Results
During a mean follow-up of 5.41 years in 793 patients, 175 patients (22.1%) reached the composite kidney endpoint. Joint modeling analysis demonstrated that a steeper decline in eGFR slope was significantly associated with a higher risk of adverse kidney outcomes (hazard ratio per 1-unit slope decrease, 1.37; P<0.001). This association remained robust across sensitivity analyses, including analyses restricted to patients with slope estimation based on ≥1.5 years of follow-up, supporting eGFR slope as a longitudinal marker of kidney disease progression in IgAN.
Conclusion
In this large, prospective IgAN cohort, eGFR slope showed a robust and independent association with kidney outcomes. Our findings support the use of eGFR slope as a reliable surrogate endpoint for clinical trials and risk stratification in IgAN.
Lay-Summary
In a large Japanese study of about 800 patients with IgA nephropathy (IgAN), researchers investigated whether changes in kidney function over time, measured by the estimated glomerular filtration rate (eGFR) slope, could predict long-term kidney outcomes. Patients were followed for an average of five years. During this time, 22% of patients experienced significant kidney decline or required kidney replacement therapy. The study found that a faster decline in eGFR was strongly associated with a higher risk of poor kidney outcomes, even after adjusting for other clinical and pathological factors. This relationship remained consistent in various additional analyses. These results suggest that the eGFR slope can serve as a reliable early marker of disease progression in IgAN. Using eGFR slope may help doctors identify high-risk patients earlier, guide treatment decisions, and improve the design of clinical trials by providing a meaningful surrogate endpoint for long-term kidney health.
