Longitudinal study of solute excretion and glomerular ultrastructure in an experimental model of aging rats free of kidney disease.

Because experimental studies of kidney aging are frequently complicated by the presence of renal disease, we set out to define a model minimizing renal pathology and thus revealing basic aging phenomena. Male and female Wistar/Lou rats were conceived, born, and bred to 42 months in a specific pathogen-free husbandry. They had free access to water and to a protein diet containing 2% fish and 15% vegetable proteins. The mean survival ages of this colony were 39 months for females and 35 months for males. Body weight, 24-hour food and water intake, urinary volume, and solute excretion were measured every 6 months in a group of 12 males and 12 females. Throughout the study, the mean body weight remained close to 180 gm in females and 320 gm in males. Despite this size difference, absolute daily food intake was similar in the two sexes and almost constant over the studied period. Age-related changes in proteinuria and phosphate excretion were greater in males than in females. Decreased urine osmolality and increased urinary volume, on the other hand, were more pronounced in old females than in males. Renal loss of calcium was noticed in both sexes and glucosuria remained discrete. Kidneys examined at 12, 24, and 36 months in both sexes and also at 42 months in females were free of major pathology such as pronounced glomerulosclerosis, tubular nephrosis, tubular cast, or hydronephrosis. In the oldest animals a few foci of interstitial inflammation occasionally were seen. The sole significant morphologic change was a regular but moderate thickening of the glomerular basement membrane, which roughly doubled its size from 12 to 36 months. Morphometric studies failed to demonstrate an increase in mesangial matrix or mesangial cellularity. No changes in foot processes, slit diaphragms, or endothelial fenestrae were seen with increasing age. These observations indicate that basic age-related changes in kidney structure and function of rats fed ad libitum can be reduced to a few parameters provided that adequate strains, diet, and husbandry conditions are selected for experimentation.