Changes seen in the aging kidney and the effect of blocking the renin-angiotensin system

The objective was to evaluate structural changes of glomeruli during aging and the role of chronic renin-angiotensin system inhibition (RASi) on these changes; starting RASi on Wistar rats at two different moments: the first group after weaning and the second at the midpoint of their lifespan (12 months).

Thirty rats were divided, after weaning, into three groups of 10: group 1: control (C); group 2 : 30 mg/kg/day losartan (L); group 3 : 10 mg/kg/day enalapril (E). At 18 months, rats were placed in metabolic cages to evaluate proteinuria, then killed. Another group of 24 rats, 12 months old, were divided into three groups of eight: group 1: C; group 2: L; group 3: E. At 18 months the same procedure described above was carried out. Finally, a third group of 20 rats was studied as healthy controls and killed: 10 rats at 7 months and ten at 12 months of age. Tissue samples were collected after sacrifice. To evaluate glomerular fibrotic changes, both focal and periglomerular sclerosis, and mesangial matrix expansion, a scoring scale was established. We also evaluated anti-alpha-SM-actin and anti-collagen-III immunolabeling. Glomerular area was measured using an image analyzer.

Proteinuria and serum creatinine increased with age but were reduced in treated animals. Main glomerular changes present in 18-month-old rats were reduced by half in treated animals. Glomerular area showed significant increase with normal aging and all treatment strategies protected against it.

RAS plays a central role in natural process of renal aging, probably by producing effects influencing the biology of aging, the effects of which can be attenuated by RASi.