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The Early Effects of Dietary Restriction on the Pathogenesis of Chronic Renal Disease in Sprague-Dawley Rats at 12 Months

Department of Veterinary Pathobiology, Univeristy of Illinois College of Veterinary Medicine, Urbana, Illinois 61801

C. Ynthia R. Long

University of Iowa, Division of Biostatistics, College of Medicine, Iowa City, Iowa 52242

Keith A. Soper

Department of Biometrics Research, Merck Research Laboratories, West Point, Pennsylvania 19486

Peter F. Smith

Searle, 4901 Searle Parkway, Skokie, Illinois 60077

Wanda M. Haschek-Hock

Department of Veterinary Pathobiology, Univeristy of Illinois College of Veterinary Medicine, Urbana, Illinois 61801

Kevin P. Keenan

Department of Safety Assessment, Merck Research Laboratories, WP45-222, West Point, Pennsylvania 19486

This study evaluated the effects of different diets and dietary regimens on the pathogenesis of chronic renal disease (CRD) in Sprague-Dawley rats at 52 wk and correlated these data with survival at 106 wk. A commercial diet (5002) was compared to a modified diet (5002-9) with less protein, fat, and energy and more fiber. Both diets were fed by ad libitum (AL) or dietary restriction (DR) regimens. The glomerular area (GA), glomerular sclerotic index (GSI), tubulo-interstitial index (TII), and tubular labeling index (tubular LI) were measured. The 5002-9 diet fed AL did not decrease the severity of CRD or increase survival, nor did the 5002 diet fed 6.5 hr/day. Both diets fed by DR did improve CRD and survival. Both AL groups had higher indices, and the 5002 AL males had the highest GA and GSI. These data indicate that the initial events in CRD occur as glomerular hypertrophy. Because the TII and tubular LI were only increased with advanced CRD, tubulo-interstitial damage did not occur until the glomerular changes were established. The 52-wk glomerular indices correlated with survival at 106 wk. Increased GA at 52 wk predicted low survival rates at 106 wk. These findings support a hypothesis that glomerular sclerosis and tubulo-interstitial damage occur secondary to early initial glomerular hypertrophy that is mitigated by caloric restriction.

Key Words: Glomerular hypertrophy • rat survival • chronic nephropathy • glomerular sclerosis • caloric restriction • protein restriction

Toxicologic Pathology, Vol. 21, No. 6, 528-537 (1993)
DOI: 10.1177/019262339302100602


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