Date of Award
Doctor of Philosophy
Roy E. Beauchene
Jane R. Savage, Rossie L. Mason, Grayce Goertz, Mary Rose Gram
The influence of diet and feed restriction on kidney function was studied in aging male albino rats. Rats were fed either a commercial feed (LB) or a modified human diet (MHD) from weaning until sacrifice at either 12 or 24 months of age. Animals sacrificed at 12 months of age were either restricted or fed LB ad libitum from 1 month of age until sacrifice. Animals fed LB and sacrificed at 24 months of age were restricted for one of the following intervals: A, no restriction; R, restriction from 1 month to 12 months; AR, restriction from 12 to 24 months. Animals eating MHD were either restricted or ad libitum-fed from 1 month to 24 months of age. Restriction was accomplished by making feed available for only 15 out of each 48 hours and resulted in terminal body weights of group R which were 66% as great as those of group A. Terminal body weights of groups AR and RA were 84 and 87%, respectively, those of group A.
Calculated growth rate (k) based on first year data was slower for animals fed a restricted level of LB as compared to those fed ad libitum. However, there was no difference in growth rates for these animals was not different from that for rats eating a restricted level of LB.
Biochemical parameters considered to be measures of kidney function and used in this study included tests for urinary protein, creatinine and osmolarity, blood urea nitrogen (BUN) and serum creatinine, in vitro transport of paraaminohippuric acid (PAH) by kidney slices and sodium-potassium-activated-adenosine triphosphatase (Na-K-ATPase) activity of kidney microsomes. Kidneys were also examined microscopically for lesions which might be expected to impair kidney function.
Results showed an absence of kidney lesions in animals restricted from 1 month of age, and only 1 rat (8%) in the group fed ad libitum to 12 months before restriction was begun (AR) showed evidence of inflammation, and this was only moderate. In contrast, 50% of rats fed MHD ad libitum and 67% of those similarly fed LB had moderate to severe lesions by the time they were sacrificed at 24 months. The magnitude of proteinuria was positively correlated with lesion scores for ad libitum-fed rats.
Urine volume increased with age only for ad libitum-fed rats eating MHD but tended to do so for those similarly fed LB. Urinary creatinine/body weight ratio was higher for groups eating MHD than for those eating LB. Urinary creatinine/body weight ratio decreased more between 15 and 21 months of age for rats fed ad libitum throughout the study and for those of group RA than for animals restricted throughout or those of group AR. Urinary protein increased much more with age of ad libitum-fed than of restricted (at any time) animals eating either diet. Urine osmolarity was complicated by influence of feeding pattern as well as by kidney performance.
Serum creatinine and BUN levels were influenced more by type of diet than by feeding patterns with the former parameter being higher for animals eating MHD than for those eating LB, and the latter, lower. There was a tendency toward higher BUN levels for ad libitum-fed than for restricted rats eating LB.
Total PAH transport was higher by kidney slices from young than from old rats, by restricted (at any time) than by ad libitum-fed ones and by those fed MHD than by those similarly fed LB. There were tendencies toward decreasing activity of Na-K-ATPase (as percent of total ATPase) with age and toward lower activity by microsomes from kidneys of rats eating MHD than by those eating LB. There was a slight tendency toward higher activity by restricted than ad libitum-fed animals of the same age eating LB.
In general, feed restrictions during either the first, the second or both years of the life of a rat was beneficial in delaying age-associated changes in kidney function as measured by PAH transport, proteinuria and kidney lesions. BUN levels and serum and urinary creatinine levels tended to be influenced favorably by restriction. Most parameters were modified by diet as well as by restriction with kidney performance being generally improved in animals eating MHD as compared with those comparably fed LB. Differences in kidney function among treatment groups may have been related to growth rates as well as intakes of calories and/or protein.
Tucker, Sarah May, "Influence of Diet and Feed Restriction on Kidney Function in Aging Male Rats. " PhD diss., University of Tennessee, 1974.