Nephron Number and Kidney Outcomes in IgA Nephropathy

Key Points No previous studies have examined the clinical significance of nephron number in patients with IgA nephropathy. In patients with IgA nephropathy, a lower number of nephrons per kidney was significantly associated with an increased rate of subsequent decline in kidney function. These findings highlight the utility of incorporating this metric into diagnostic evaluations to help assess risk and tailor treatment for IgA nephropathy. Background We previously reported substantial variability in the number of nephrons in patients with IgA nephropathy, even among patients with similar risk factor profiles. This retrospective cohort study aimed to evaluate the clinical significance of nephron number at diagnostic biopsy for subsequent kidney outcomes in patients with IgA nephropathy. Methods The number of nephrons, defined as the total number of nonglobally sclerotic glomeruli per kidney, was estimated using computed tomography imaging and biopsy-based stereology. Kidney outcomes were compared based on tertiles of nephron number. The primary end point was the annual slope of the eGFR, and the secondary end point was the initiation of KRT. Results A total of 222 Japanese adults with IgA nephropathy were included. Among the entire cohort, eGFR exhibited a gradual decline over time during a median follow-up of 7.6 years. Annual eGFR slopes, adjusted for baseline eGFR, baseline proteinuria, Oxford classification scores, and therapies during the first year after biopsy, were −1.35, −1.11, and −0.97 ml/min per 1.73 m 2 per year for the lowest to highest nephron number tertiles, respectively ( P for trend <0.001). KRT was initiated in 32.4%, 10.8%, and 0% of patients in the lowest, middle, and highest tertiles, respectively ( P for trend <0.001). A significantly higher risk of KRT initiation with decreasing number of nephrons was confirmed using multivariable adjusted Cox proportional hazards models. Conclusions Lower number of nonglobally sclerotic glomeruli per kidney identified at diagnostic biopsy was independently associated with increased rate of future kidney functional decline in patients with IgA nephropathy, providing additional information beyond conventional clinical and histopathologic risk factors. Incorporating this metric into routine evaluation may enhance risk stratification and inform more personalized, targeted treatment strategies for patients with IgA nephropathy.