Single-nephron eGFR and kidney function decline in IgA nephropathy

Abstract Introduction During the progression of IgA nephropathy (IgAN), residual nephrons compensate for nephron loss by increasing single-nephron estimated glomerular filtration rate (eGFR). This adaptive hyperfiltration may accelerate the decline in kidney function. However, due to measurement challenges, the prognostic value of single-nephron eGFR remains unclear. This study investigates its impact on kidney function decline in patients with IgAN. Methods This observational cohort study included 187 biopsy-confirmed IgAN patients who had undergone computed tomography and biopsy during their hospitalization. Single-nephron eGFR was estimated by dividing total eGFR by nephron number, the latter of which was derived from the cortical volume and glomerular density. The primary composite outcome was kidney function decline, defined as a sustained annual eGFR decrease of ≥5 mL/min/1.73m2, a ≥ 40% reduction in eGFR from baseline, or end-stage renal disease (ESRD). Cox proportional hazards models were fit to estimate associations between single-nephron eGFR and kidney function decline. Results Among the 187 participants (45% women, mean age 38 ± 11 years), 57 experienced a decline in kidney function over a median follow-up period of 3.1 years. Participants were divided into three groups based on their single-nephron eGFR. Kaplan-Meier analysis demonstrated significantly reduced kidney survival in the high single-nephron eGFR group compared to the low and middle groups (log-rank P 0.001). Compared to the low single-nephron eGFR group, multivariable hazard ratios for kidney function decline were 2.50 (95% CI 1.10–5.67; P = 0.03) for the middle group and 5.30 (95% 2.44–11.54; P 0.001) for the high group. Conclusions A higher single-nephron eGFR is identified as a risk factor for kidney function decline in patients with IgAN, which supports its potential as an early risk-stratification tool. Moreover, using eGFR cutoffs alone to define hyperfiltration may lead to misclassification due to its inability to distinguish patients with hyperfiltration from those without.