(A) Method and assumptions. The normal reduction in podocyte density by age is illustrated by the diagonal solid line as previously reported (17). Open circles represent hypothetical kidney donation ages at 20, 40, and 60 years. At implantation both the kidney and glomerulus rapidly increase in size by 20% (19). Podocytes cannot divide and therefore have to undergo rapid compensatory hypertrophy, resulting in reduced podocyte density, as shown by the dotted line at each donor age. Following implantation, allografts continue to lose podocytes at an increased rate on average 6-fold above the native kidney control rate (19). This increased rate of podocyte detachment will result in an accelerated rate (steeper slope compared with native kidneys) of further reduction in podocyte density (dashed lines). At a podocyte density value below 50 per 10⁶ μm³, global sclerosis will supervene and kidneys will be at end-stage kidney disease (ESKD). The predicted time to ESKD can therefore be estimated for any putative donor age, as shown by the arrowheads. The observed mean value for time to ESKD for deceased donor kidney transplants at each of the three donor ages is shown at right as derived from the OPTN/UNOS database as of September 5, 2014. (B) Comparison of projected to observed kidney transplant half-life by age. Each data point (n = 89) from the previously reported aging study (17) was used to estimate the projected time to ESKD that would have occurred were that kidney to have been transplanted according to the above criteria. The regression line ± 95% confidence limit is shown. The closed triangles show aggregated half-lives by age for deceased donors as derived from the OPTN/UNOS database as of September 5, 2014. The slope of the linear regression line derived from podometric data (solid line) is steeper than the observed OPTN/UNOS data, although this difference is not statistically significant (P = 0.42; general linear model).