Calorie restriction decreases microalbuminuria associated with aging in barrier-raised Fischer 344 rats

Abstract

Renal function as a sensitive biomarker of aging has been studied in specific pathogen-free (SPF) Fischer 344 rats (n = 211), and results are presented according to animal age (5, 8, 12, 18, 24 mo), sex, and diet (ad libitum vs. 40% calorie restriction). Plasma creatinine concentration, endogenous creatinine clearance, total protein excretion, and albumin excretion were measured. Kidney histology was evaluated by light microscopy. In both calorie-restricted and ad libitum-fed animals, kidney weight (KW) and body weight (BW) showed parallel changes with age. The KW-to-BW ratio was unaffected by age in all groups. There was no alteration in plasma creatinine concentration as a function of age or diet. In these SPF animals there was also no change in glomerular filtration rate with age. In animals fed ad libitum, albumin and protein excretion increased with age (females: 0.39 +/- 0.05 at 5 mo vs. 7.4 +/- 2.6 mg protein.24 h-1.g KW-1 at 24 mo; males: 4.1 +/- 0.6 at 5 mo vs. 15 +/- 3 mg protein.24 h-1.g KW-1 at 24 mo). The higher protein excretion rate in all males at 5 mo reflected the excretion of sex-dependent low-molecular-weight proteins that commenced with sexual maturation. Calorie restriction prevented the age-dependent increase in total protein excretion. Kidney histopathology was positively correlated with total protein and albumin excretion. Microalbuminuria preceded the development of lesions detectable by light microscopy. These observations support the concept that microalbuminuria in this model is a sensitive and early biomarker of nephropathy that can be monitored easily and noninvasively.