An Improved Method for Estimating Nephron Number and the Association of Resulting Nephron Number Estimates with Chronic Kidney Disease Outcomes.

Abstract

Nephron number can be estimated from glomerular density and cortical volume. However, because of measurement biases, this approach needs refinement, comparison between disparate populations, and evaluation as a predictor of CKD outcomes. We studied 3020 living kidney donors and 1354 patients who underwent radical nephrectomy for tumor. We determined cortex volume of the retained kidney from presurgical imaging and glomerular density by morphometric analysis of needle core biopsy of the donated kidney and wedge sections of the removed kidney. Glomerular density was corrected for missing glomerular tufts, absence of the kidney capsule, and then tissue shrinkage on the basis of analysis of 30 autopsy kidneys. We used logistic regression (in donors) and Cox proportional hazard models (in patients with tumor) to assess the risk of CKD outcomes associated with nephron number. Donors had 1.17 million nephrons per kidney; patients with tumor had 0.99 million nephrons per kidney. A lower nephron number was associated with older age, female sex, shorter height, hypertension, family history of ESKD, lower GFR, and proteinuria. After adjusting for these characteristics, nephron number did not differ between donors and patients with tumor. Low nephron number (defined by <5th or <10th percentile by age and sex in a healthy subset) in both populations predicted future risk of CKD outcomes independent of biopsy and clinical characteristics. Compared with an older method for estimating nephron number, a new method that addresses several sources of bias results in nephron number estimates that are 27% higher in donors and 1% higher in patients with tumor and shows consistency between two populations. Low nephron number independently predicts CKD in both populations.