Nephron Number and Kidney Outcomes in IgA Nephropathy: A Retrospective Cohort Study.

Background: We previously reported substantial variability in the number of nephrons in patients with IgA nephropathy (IgAN), 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 IgAN.

Methods: The number of nephrons, defined as the total number of non-globally 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 endpoint was the annual slope of the estimated glomerular filtration rate (eGFR), and the secondary endpoint was the initiation of kidney replacement therapy.

Results: A total of 222 Japanese adults with IgAN 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/1.73 m2/year for the lowest to highest nephron number tertiles, respectively (P for trend < 0.001). Kidney replacement therapy 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 kidney replacement therapy initiation with decreasing number of nephrons was confirmed using multivariable adjusted Cox proportional hazards models.

Conclusions: Lower number of non-globally sclerotic glomeruli per kidney identified at diagnostic biopsy was independently associated with increased rate of future kidney functional decline in IgAN patients, providing additional information beyond conventional clinical and histopathological risk factors. Incorporating this metric into routine evaluation may enhance risk stratification and inform more personalized, targeted treatment strategies for patients with IgAN.