Quantitative podocyte parameters predict human native kidney and allograft half-lives.
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.


CONCLUSIONS
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.


BACKGROUND
National Institutes of Health.
Department of Internal Medicine.
Abhijit S
AS
Naik
Department of Internal Medicine.
Farsad
F
Afshinnia
Department of Internal Medicine.
Diane
D
Cibrik
Department of Pathology.
Jeffrey B
JB
Hodgin
School of Public Health, and.
Fan
F
Wu
School of Public Health, and.
Min
M
Zhang
Department of Internal Medicine.
Masao
M
Kikuchi
Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan, USA.
Larysa
L
Wickman
Department of Internal Medicine.
Milagros
M
Samaniego
Department of Internal Medicine.
Markus
M
Bitzer
Department of Internal Medicine.
Jocelyn E
JE
Wiggins
Department of Internal Medicine.
Akinlolu
A
Ojo
School of Public Health, and.
Yi
Y
Li
Department of Internal Medicine.
Roger C
RC
Wiggins