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

Abstract

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.

Diet, Overfeeding, and Moderate Dietary Restriction in Control Sprague-Dawley Rats: II. Effects on Age-Related Proliferative and Degenerative Lesions

“…These qualitative observations were stereologically quantified and the determination of GA, the GSI, the TII and the BrdU % LI support our recently proposed hypothesis for the pathogenesis of spontaneous CRD ( 17). Two (6,50).…”

“…The experimental groups contained 70 (8,59 (12,17). The glomerular area (~m2) was determined from the glomerular circumference using computerized planimetry on each animal (17,75 (17).…”

“…The glomerular area (~m2) was determined from the glomerular circumference using computerized planimetry on each animal (17,75 (17). The TII was modified from the method of Tapp et al (70).…”

The Effect of Chronic Progressive Nephropathy on the Incidence of Renal Tubule Cell Neoplasms in Control Male F344 Rats

“…The gross and microscopic features of CPN as well as the inuences of strain, age, sex, and diet have previously been described (1)(2)(3)(4)(5). The incidence and severity of CPN can be affected by castration, hormonal status, or caloric intake (6,7). Chemical treatment may also alter CPN often enhancing its incidence, severity, and onset (8).…”

Diabesity: A Polygenic Model of Dietary-Induced Obesity from Ad Libitum Overfeeding of Sprague–Dawley Rats and Its Modulation by Moderate and Marked Dietary Restriction

“…Therefore, targeting the metabolic syndrome as a whole rather than specifically dissecting each one of its subcomponents should be considered as a key objective in the development of models to test treatments and management programs of this important human syndrome. In this regard, the Charles River outbred SD rat appears to represent an excellent polygenic model that is only now beginning to be thoroughly phenotyped and understood from the perspective of an animal model of diabesity (Gumprecht et al, 1993;Klinger et al, 1996;Keenan et al, 1997Keenan et al, , 1994aKeenan et al, , 1994bKeenan et al, , 1995Keenan et al, , 1996Keenan et al, , 1999Keenan et al, , 2000aKeenan et al, , 2000bHubert et al, 1997Hubert et al, , 2000Laroque et al, 1997;Levin et al, 1997Levin et al, , 2000Hoe et al, 1998;Vermorel et al, 1998;Molon-Noblot et al, 2001Kemi et al, 2000). While not all of the phenotypic and genetic characteristics of this stock have yet been well defined, the results of this study and previous work indicate that when ALfed this animal clearly has a well-developed set of phenotypic characteristics that would be best described as diabesity.…”