More than half of all end-stage kidney disease (ESRD) patients are now over the age of 65. The fastest growing population on the kidney transplant waiting list is the elderly. Elderly patients on the transplant waiting list are vulnerable to declining health and an increasing mortality rate while on the waiting list. Consequently, there has been a substantial rise in the use of older donors, both living and deceased, in their 7th of 8th deceases. Older donors, whether deceased of living, have been reluctantly used for kidney transplantation because survival from of a kidney transplant from an aging donor is much shorter than from a younger donor. This age group is prone to an insidious renal vasculopathy and glomerulopenia, superimposition of with on a single, senescent kidney could result in the "remnant kidney" phenomenon with progressive chronic kidney disease. By year 05 of this grant, I will complete recruitment into a longitudinal study of a group (N=30) of aging, living donors (>55 years). A matching group of youthful living donors (<45 years) will serve as controls. I will also initiate a cross-sectional study of older living donors who donated a kidney 10-20 years ago at age >55 years to evaluate longer term outcome. In addition to elucidating the pathophysiology of chronic kidney disease in older donors who have undergone kidney donation, my goal is to conduct a detailed study of renal senescence in healthy older individuals who undergo the process of kidney donation and to use the information gained in this study to establish evidence-based guidelines for organ allocation in the elderly. The largest increase in the incidence of ESRD is in the population over 65, with a parallel increase in the elderly awaiting kidney transplant. Even larger numbers of elderly persons have CKD not requiring dialysis. A central question in chronic kidney disease will shift toward the care of the elderly. My goal is to determined evidence-based guideline for selection of elderly individuals for safe transplantation and donation.

Public Health Relevance

Aging donors, whether deceased or living, are reluctantly used for kidney transplantation (Tx) because survival of an allograft from an aging donor is much shorter than from a younger donor. Notwithstanding the limited efficacy, a growing shortfall of kidneys for Tx has led to increasing use of aging donors, both living and deceased, in their 7th or 8th decades. This age group is prone to an insidious renovasculopathy and glomerulopenia, superimposition of which on a single, senescent kidney could result in the remnant kidney phenomenon with progressive renal failure. By year 05 of the present grant, we will complete recruitment into a longitudinal study of a group (N=30) of aging, living donors (>55). A matching group of youthful living donors (<45 yr) will serve as controls. We now wish to build on this unique data base to permit longitudinal evaluation of each aging and youthful living donor for 48 months. We will also initiate a cross-sectional study of aging living donors who donated a kidney 10-20 years ago at age >55 years to evaluate longer term outcome. Youthful case controls (N=30-50) will have donated when <40 yr. In addition to elucidating the pathophysiology of chronic kidney failure in uninephric, aging donors, we hope to predict such failure from baseline findings at Tx, thereby facilitating optimal selection of aging donors for Tx in the future.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23DK087937-05
Application #
8662248
Study Section
Special Emphasis Panel (ZDK1-GRB-G (J2))
Program Officer
Rankin, Tracy L
Project Start
2010-06-01
Project End
2015-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
5
Fiscal Year
2014
Total Cost
$178,476
Indirect Cost
$13,186
Name
Stanford University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Lenihan, Colin R; Tan, Jane C (2014) The consequences of chronic kidney disease mislabeling in living kidney donors. Mayo Clin Proc 89:1126-9
Lenihan, Colin R; Hurley, Michael P; Tan, Jane C (2013) Comorbidities and kidney transplant evaluation in the elderly. Am J Nephrol 38:204-11
Lenihan, Colin R; Tan, Jane C; Kambham, Neeraja (2013) Acute transplant glomerulopathy with monocyte rich infiltrate. Transpl Immunol 29:114-7
Tan, Jane C; Paik, Jane; Chertow, Glenn M et al. (2011) Validity of surrogate measures for functional nephron mass. Transplantation 92:1335-41
Lapasia, Jessica B; Kong, Soo-yee; Busque, Stephan et al. (2011) Living donor evaluation and exclusion: the Stanford experience. Clin Transplant 25:697-704