Distinguishing age-related from disease-related glomerulosclerosis on kidney biopsy: The Aging Kidney Anatomy study

Background. Global glomerulosclerosis is characteristic of chronic kidney disease and also occurs with normal aging. Our goal was to determine the upper limit of normal for number of globally sclerotic glomeruli. Methods. Core-needle biopsies of the renal cortex were obtained at the time of living kidney transplantation at three centers between 1998 and 2011. The number of globally sclerotic glomeruli was averaged across two biopsy sections. Quantile regression was used to estimate the 95th percentile for globally sclerotic glomeruli as the upper reference limit. There were 2052 donors (mean age 43 years, 41% male, 10% hypertensive), with a mean (SD) of 16.0 (9.7) glomeruli and 0.47 (0.99) globally sclerotic glomeruli on biopsy; only 2.6% had >5% fibrosis. Results. In a multivariable model excluding hypertensive donors, independent predictors of the number of globally sclerotic glomeruli were age, total number of glomeruli and cortex area. A simplified model was used to estimate the 95th percentile for number of globally sclerotic glomeruli by total number of glomeruli and age. For a biopsy section with 17-32 total glomeruli, the 95th percentile ranged from 1 for a 20-year old to 5.5 for a 70-year old donor. Hypertensive donors were more likely to have an abnormal number of globally sclerotic glomeruli (OR = 1.79, P = 0.035). Conclusions. We have derived the 95% reference limit for number of globally sclerotic glomeruli in ostensibly healthy individuals accounting for age and the biopsy characteristics. Numbers of globally sclerotic glomeruli in a kidney biopsy that exceed these thresholds suggest chronic pathological injury in excess of that expected with normal aging.