URINARY-EXCRETION OF CATHEPSIN-B AND CYSTATINS AS PARAMETERS OF TUBULAR DAMAGE

The urinary excretion of the lysosomal hydrolases cathepsin B and beta -N-acetylglucosaminidase (beta-NAG) was compared with the tubular acti vities of these enzymes in remnant kidneys 16 weeks after subtotal nep hrectomy (5/6 NX) or unilateral nephrectomy (UNX), as well as in kidne ys from diabetic rats. In addition, the urinary excretion of the low-m olecular weight protein cystatins, inhibitors of lysosomal cathepsins, was also followed in these animals. The urinary excretion of cathepsi n B and beta-NAG was significantly enhanced in all three models of ren al disease. The highest excretion rates for these enzymes were found i n diabetic animals (cathepsin B: 4-fold; beta-NAG: more than a 10-fold increase over respective controls). In terms of tubular enzyme activi ties, tissue activities of both hydrolases were reduced in the remnant kidney after 5/6 NX, while in UNX and diabetes only cathepsin B activ ity was decreased. The urinary excretion of cystatins was enhanced in all three animal models, particularly in 5/6 nephrectomized rats, wher e a 40-fold increment over control animals was observed. Taken togethe r, these findings indicate that there was severe tubular damage in the remnant kidney after 5/6 NX (reduced tubular enzyme activities, enzym uria and severely compromised tubular protein reabsorption). Furthermo re, considerable enzymuria and disturbed protein reabsorption in early diabetes suggest tubular dysfunction before signs of glomerular damag e become evident.