The tissue concentration of tubular marker enzymes were evaluated in sections of kidneys from 86 patients with various underlying diseases such as hydronephrosis, interstitial nephropathies, ischemia due to renal arterial stenosis and chronic allograft rejection. In addition, as an experimental model, kidney tissue sections of 166 Wistar rats were analyzed due to hydronephrosis caused by ureteral obstruction, ischemia and obstruction of the renal vein. The tissue concentration of indicator enzymes, such as alkaline phosphatase (AP) and alanine-aminopeptidase (AAP), was considered as a parameter describing the extent of kidney tubule damage. Quantitative evaluation of enzymatic activity was performed by histophotometry using a computed image analysis device technique. As compared to normal human kidney (enzyme activity 100%), the concentrations of brush border enzymes were significantly (p < 0.001) lower under pathological conditions (AP < 15%, AAP < 55%). In similar manner investigations of kidneys in animal experiments with rats exhibited lower enzyme concentrations following kidney injury caused by ureteral obstruction for 10 and 21 days (AP < 12%, AAP < 65%; 2p < 0.01). Kidneys after an ischemic period of 2 h and a subsequent 14-day recirculation period displayed a significant (2p < 0.01) decrease of normally present indicator enzyme concentrations (AP < 22%, AAP < 77%) as compared to normal renal organs (100%). Computed image analysis of kidney tissue sections might be a useful aid in evaluating morphologic and enzymatic patterns of human and animal kidney alterations.
Ten informed healthy volunteers with normal renal function received 2 X 3.0 g ceftazidime on three consecutive days. The combination of the same dose of ceftazidime together with tobramycin (3 mg/kg/d) was administered four weeks later to the same group of volunteers. In the first trial with ceftazidime alone no changes in the elimination of brush-border membrane enzyme AAP were found. In contrast, the administration of ceftazidime together with tobramycin produced the expected response to tobramycin with the cumulative pattern of enzyme elimination into urine. Functional parameters remained unchanged.
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