A NEW analysis from the Japanese Japan IgA Nephropathy Cohort Study provides robust evidence supporting estimated glomerular filtration rate (eGFR) slope as a clinically meaningful surrogate endpoint in IgA nephropathy, with implications for both risk stratification and clinical trial design.
In this large cohort study, researchers evaluated 937 adults with biopsy-confirmed IgA nephropathy over a median follow-up of six years. The primary aim was to determine whether longitudinal changes in eGFR, captured as individual eGFR slopes, are independently associated with kidney outcomes beyond static eGFR measurements. Using linear mixed-effects modelling, patient-specific eGFR trajectories were calculated, and their relationship with clinical outcomes was assessed via joint modelling of longitudinal and time-to-event data.
eGFR Decline Linked to Higher Risk of Kidney Progression in IgA Nephropathy
The composite endpoint was defined as a ≥40% decline in eGFR or initiation of kidney replacement therapy. During follow-up, 78 patients (8.3%) reached this endpoint. A steeper decline in eGFR slope was strongly associated with an increased risk of adverse kidney outcomes. Specifically, each 1-standard deviation steeper decline in eGFR slope (equivalent to 0.31 mL/min/1.73 m²/year) conferred a hazard ratio of 1.82 (P < 0.001).
Importantly, this association remained significant after adjustment for baseline clinical and histopathological factors, including current eGFR levels, suggesting that eGFR slope captures prognostic information not reflected by single timepoint measurements. Sensitivity analyses supported the robustness of these findings. The relationship persisted in patients already receiving treatment at baseline, albeit with a modest attenuation in effect size, and in those with at least five recorded eGFR measurements.
These results reinforce the clinical relevance of monitoring eGFR trajectories in IgA nephropathy. While static eGFR remains central to disease assessment, dynamic measures such as slope may better reflect underlying disease activity and progression risk.
New Evidence Supports eGFR Slope for Risk Stratification in IgA Nephropathy
For clinicians and trialists, the findings provide further validation of eGFR slope as a surrogate endpoint that could enable earlier assessment of therapeutic efficacy. This is particularly pertinent in IgA nephropathy, where disease progression is often slow and traditional endpoints require prolonged follow-up.
Overall, this study strengthens the case for incorporating eGFR slope into both routine clinical evaluation and the design of interventional studies in IgA nephropathy.
Reference
Sasaki T et al. Estimated glomerular filtration rate slope and kidney outcomes in IgA nephropathy. NDT. 2026; DOI: 10.1093/ndt/gfag089.
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