Abstract
BACKGROUND. Kidney function decreases with age. A potential mechanistic explanation for kidney and allograft half-life has evolved through the realization that linear reduction in glomerular podocyte density could drive progressive glomerulosclerosis to impact both native kidney and allograft half-lives.
METHODS. Predictions from podometrics (quantitation of podocyte parameters) were tested using independent pathologic, functional, and outcome data for native kidneys and allografts derived from published reports and large registries.
RESULTS. With age, native kidneys exponentially develop glomerulosclerosis, reduced renal function, and end-stage kidney disease, projecting a finite average kidney life span. The slope of allograft failure rate versus age parallels that of reduction in podocyte density versus age. Quantitative modeling projects allograft half-life at any donor age, and rate of podocyte detachment parallels the observed allograft loss rate.
CONCLUSION. Native kidneys are designed to have a limited average life span of about 100–140 years. Allografts undergo an accelerated aging-like process that accounts for their unexpectedly short half-life (about 15 years), the observation that older donor age is associated with shorter allograft half-life, and the fact that long-term allograft survival has not substantially improved. Podometrics provides potential readouts for these processes, thereby offering new approaches for monitoring and intervention.
FUNDING: National Institutes of Health.
Authors
Abhijit S. Naik, Farsad Afshinnia, Diane Cibrik, Jeffrey B. Hodgin, Fan Wu, Min Zhang, Masao Kikuchi, Larysa Wickman, Milagros Samaniego, Markus Bitzer, Jocelyn E. Wiggins, Akinlolu Ojo, Yi Li, Roger C. Wiggins
Figure 6
Donor age in relation to allograft half-life plots.
