The Effect on Renal Structure and Function of Late-life-introduced Caloric Restriction (CR) in Rats

Previous studies have shown that life-long caloric restriction in rats protects the kidneys from age-dependent injury. In this study, we analyzed whether late-life-introduced caloric restriction has a similar effect. The study lasted 12 months. Three groups of animals were analyzed: rats fed "ad libitum" (AD, n = 9), rats on 60% caloric restriction (CR, n = 9), and rats fed "ad libitum" for the first six months of their life then switched to 60% caloric restriction thereafter (LCR, n = 9). At the end of the study kidney function was assessed and kidney samples were analyzed histologically. Serum creatinine and urine albumin were higher in AD than in both CR and LCR (P < 0.001). Creatinine clearance (Cl(cr)) corrected for body weight was lowest in AD and comparable in CR and LCR. Similarly Cl(cr) corrected for kidney weight was lower in AD than in both CR and LCR (P < 0.05). Severe albuminuria was observed only in AD. In CR and LCR the amount of albumin excreted was comparable (AD vs. CR, P < 0.0001; AD vs. LCR, P < 0.001). In morphometric analysis, the mean size of the glomeruli was higher in AD than in both CR and LCR (P < 0.01). Similar results were found for the mesangial area (AD vs. CR, P < 0.001; AD vs. LCR, P < 0.01) and for mesangial cell counts (AD vs. CR, P < 0.001; AD vs. LCR, P < 0.05). No difference was found between CR and LCR in morphometry. In conclusion, our study indicates that late-life introduction of caloric restriction reverses most of the structural and functional changes observed in the kidneys of "ad libitum"-fed rats.