TitleStructural equation modeling identifies markers of damage and function in the aging male Fischer 344 rat.
Publication TypeJournal Article
Year of Publication2016
AuthorsGrunz-Borgmann, EA, Nichols, LNA, Wiedmeyer, CE, Spagnoli, ST, Trzeciakowski, JP, Parrish, AR
JournalMech Ageing Dev
Volume156
Pagination55-62
Date Published2016 06
ISSN1872-6216
KeywordsAging, Animals, Cell Adhesion Molecules, Cystatin C, Glucuronidase, Humans, Male, Models, Biological, Proteinuria, Rats, Rats, Inbred F344, Renal Insufficiency, Chronic
Abstract

The male Fischer 344 rat is an established model to study progressive renal dysfunction that is similar, but not identical, to chronic kidney disease (CKD) in humans. These studies were designed to assess age-dependent alterations in renal structure and function at late-life timepoints, 16-24 months. Elevations in BUN and plasma creatinine were not significant until 24 months, however, elevations in the more sensitive markers of function, plasma cystatin C and proteinuria, were detectable at 16 and 18 months, respectively. Interestingly, cystatin C levels were not corrected by caloric restriction. Urinary Kim-1, a marker of CKD, was elevated as early as 16 months. Klotho gene expression was significantly decreased at 24 months, but not at earlier timepoints. Alterations in renal structure, glomerulosclerosis and tubulointerstitial fibrosis, were noted at 16 months, with little change from 18 to 24 months. Tubulointerstitial inflammation was increased at 16 months, and remained similar from 18 to 24 months. A SEM (structural equation modeling) model of age-related renal dysfunction suggests that proteinuria is a marker of renal damage, while urinary Kim-1 is a marker of both damage and function. Taken together, these results demonstrate that age-dependent nephropathy begins as early as 16 months and progresses rapidly over the next 8 months.

DOI10.1016/j.mad.2016.04.011
Alternate JournalMech. Ageing Dev.
PubMed ID27134149
Grant ListR01 AG034154 / AG / NIA NIH HHS / United States