The aging rat kidney displays low glomerular and tubular proteinase activities

The present study was conducted to investigate the relationship of age-related changes in renal function and structure with changes in glomerular and tubular proteinase activities in young (3 weeks), mature (3 months), and older (18 months) male Wistar rats. Glomerular filtration rate, expressed per 100 g body weight, remained unchanged during adolescence, but declined significantly (-44%) in aging animals. In parallel, albuminuria, which was barely detectable in young and mature rats, increased almost 10-fold in the aging animals. In comparison to young animals, the kidney weight in aging rats was 10-fold higher, signifying considerable tubular hypertrophy. The glomerular protein to DNA ratio increased by almost 70%, suggesting deposition of mesangial matrix within the glomerulus. These structural changes were associated with significant reductions in glomerular cysteine and metalloproteinase activities in the adolescent and older animals. Similarly, lower activities of both types of proteinases were observed in isolated proximal tubules. This behavior of proteolytic enzyme activities in the aging rat kidney corresponds well to the 10-fold increase in kidney weight (proximal tubular hypertrophy) and to the enhanced deposition of glomerular matrix. This study suggests a causal involvement of renal cysteine proteinases and metalloproteinases in the protein accumulation of the aging rat kidney.