Urinary Excretion Of Alanine Aminopeptidase Research Articles

Gamma-Glutamyltransferase is a Reliable Marker for Tubular Effects of Contrast Media

The aim of this study was to evaluate the usefulness of the measurement of urinary excretion of the brush-border enzyme gamma glutamyltransferase (GGT), in comparison with that of alanine aminopeptidase (AAP), as a marker for tubular toxicity due to contrast media (CM).Urinary activities of AAP and GGT were measured prior to the ad-ministration of CM and 1, 3 and 5 days after in forty-nine adult renal patients undergoing a radiological examination with intravascular ad-ministration of CM.The behavior of GGT was similar to that of AAP. In fact, urinary activities of both AAP and GGT increased greatly after CM. This effect was maximal on the 1st day and statistically significant for both enzymes. Furthermore, on the 1st day a relevant increase of enzyme activity (at least +50% over the basal value) was observed in the same number of patients (67%) for AAP and GGT The concordance between GGT and AAP variations was high and statistically significant. Finally, different variables (osmolarity, dose of CM, and baseline renal function of the patients) had a similar effect on urinary excretion of AAP and GGT.The repeatability of duplicated determinations of GGT resulted better than that of AAP. In conclusion, the good concordance of the results of GGT with those of AAP justifies the use of GGT as a marker for tubular effects due to CM. Furthermore, the measurement of GGT has a better repeatability than that of AAP.

Possible use of excretion of tubular epithelial cells for the study of the nephrotoxic effect of xenobiotics

The method of determination of the minute excretion of tubular epithelial cells renders it possible to investigate the course of the nephrotoxic effect of the toxin by the influence of which excretion of tubular round epithelial cells is increased. The nephrotoxic effect of repeated administration of amphotericin B (1 mg/kg, i.v.), which produced up to 12-fold increases in the number of excreted epithelial cells, was examined. Repeated administration of cyclosporin A (45 and 56 mg/kg, p.o.) produced up to 23-fold increases in the number of excreted epithelial cells. The degree of excretion of epithelial cells after administration of both drugs was compared with the urinary excretion of alanine aminopeptidase and N-acetyl-β- d-glucosaminidase, which indicated nephrotoxicity in amphotericin B and cyclosporin A with a lower sensitivity than the increase in the excretion of epithelial cells. In the experiment with cyclosporin A, urinary excretion of epithelial cells was further correlated with renal functional tests (clearance of polyfructosan and hippurate).

Comparison of Halothane, Enflurane and Isoflurane Kidney Effects through Alanine Aminopeptidase/Urine Creatinine Values

The kidney effects of halothane, enflurane and isoflurane were evaluated by using the ratio of urinary excretion of alanine aminopeptidase (AAP) to urine creatinine. Thirty patients in ASA class 1 or 2 were studied. None had renal disease nor received nephrotoxic drugs. Groups 1, 2 and 3 received halothane, enflurane and isoflurane respectively. Creatinine and AAP activities in urine spot tests, serum creatinine and BUN levels were determined preoperatively and on the first and second postoperative days. Urine AAP activity and AAP/urine creatinine values increased significantly on the first and second postoperative days compared with the preoperative values in all groups (P < 0.05). The present study did not reveal any significant difference in the kidney effects of halothane, enflurane and isoflurane through AAP/creatinine in spot urine values.

Age-Dependent Excretion of Alanine Aminopeptidase, Alkaline Phosphatase, γ-Glutamyltransferase and N-Acetyl-β-D-Glucosaminidase in Human Urine

Urinary excretion of alanine aminopeptidase, alkaline phosphatase, gamma-glutamyltransferase and N-acetyl-beta-D-glucosaminidase was determined in gel-filtered samples of morning random urine specimens of 442 subjects of various ages (5 days to 58 years). Enzyme excretion related to urinary creatinine (enzyme/creatinine ratio; U/mmol creatinine) significantly decreased with increasing age. Sex-related differences of some enzyme excretions were found in age groups over 6 years. From these investigations, we calculated upper reference intervals (97.5 percentiles) for 5 age-dependent groups of children and adolescents and for one group of adults.

Urinary Output Modulation of Alanine Aminopeptidase, γ-Glutamyl Transpeptidase and N-Acetyl-ß-D-Glucosaminidase by Castration and Testosterone in Male Normal Rat

The urinary excretion of alanine aminopeptidase (AAP), gamma-glutamyl transpeptidase (gamma-GT) and of N-acetyl-beta-D-glucosaminidase (NAG) was studies in normal and castrated rats receiving either testosterone for 5 post-operative weeks or no hormone. In castrated rats the urinary output of AAP and gamma-GT was significantly lower than in sham control or in castrated rats receiving testosterone. In addition, an excess of exogenously given testosterone had no effect on enzymuria of normal rats. The urinary excretion of NAG was influenced neither by castration nor by testosterone. These results suggest that endogenous testosterone is responsible for a permanent positive control on the urinary excretion of AAP and gamma-GT.

The Increase in Urinary Alanine Aminopeptidase Excretion Associated with Enflurane Anesthesia Is Increased Further by Aminoglycosides

Urinary excretion of alanine aminopeptidase (AAP) is an extremely sensitive indicator of drug-induced renal tubular damage. The urinary excretion of AAP was determined in patients after enflurane anesthesia with or without concurrent aminoglycoside administration to determine if enflurane enhances the nephrotoxic potential of aminoglycosides. Twenty-two patients with normal renal function were studied. Ten received enflurane alone, eight received enflurane plus gentamicin or tobramycin, and four patients who underwent nitrous oxide and narcotic anesthesia were the control group. Preoperative values ranged from 1010 to 2461 microU/24 hour. Urinary AAP excretion increased significantly in both enflurane groups 2 days postoperatively (P less than 0.025). Patients who received both enflurane and aminoglycosides had significantly greater urinary AAP excretion on postoperative day 2 than did patients given enflurane alone: 21,342 +/- 4074 microU/24 hour and 6336 +/- 1496 microU/24 hour, respectively (mean +/- SEM, P less than 0.005). There was no change in AAP excretion in the control group compared to baseline; on day 3 AAP was 1412 +/- 710 microU/24 hour. No changes in blood urea nitrogen or serum creatinine levels were observed. These data suggest that enflurane increases the renal tubular effects of aminoglycosides, possibly increasing the risk of aminoglycoside renal toxicity.

Mercuric chloride-induced nephrotoxicity in the rat following unilateral nephrectomy and compensatory renal growth.

The nephropathy induced by mercuric chloride was assessed in unilaterally nephrectomized (NPX) and sham-operated (SO) rats using histological and urinalysis techniques. This assessment was carried out in order to test whether or not rats are more susceptible to the nephrotoxic effects of mercuric chloride after unilateral nephrectomy and a period allowing for compensatory renal growth. Twelve days after surgery both NPX and SO rats were given a single 1.5, 2.0 or 2.5 mumol/kg dose of mercuric chloride (i.v.). Twenty-four hours after the 1.5 or 2.0 mumol/kg dose of mercuric chloride was administered, cellular and tubular necrosis in the pars recta segments of proximal tubules in the outer medulla was more severe in NPX rats than in SO rats. Moreover, the urinary excretion of a number of cellular enzymes (e.g. lactate dehydrogenase) and plasma solutes (e.g. albumin) was greater in NPX rats than in SO rats. At the 2.5 mumol/kg dose of mercuric chloride, renal tubular damage was quite extensive in both groups of rats; to such an extent that possible differences in renal tubular damage between the NPX and SO rats could not be determined histologically. However, the urinary excretion of alanine aminopeptidase was greater in the NPX rats than in the SO rats. Therefore, based on the aforementioned findings, rats that have undergone and adapted to a reduction in renal mass (i.e. unilateral nephrectomy) appear to be more vulnerable to the nephrotoxic effects of mercuric chloride than rats with two normal kidneys.

Cumulative renal tubular damage associated with cisplatin nephrotoxicity.

We assessed the acute and chronic effect of multiple courses of cisplatin therapy on renal tubules by monitoring the urinary excretion of alanine aminopeptidase, N-acetyl-beta-D-glucosaminidase, and total protein. Urine specimens were obtained before and after doses of cisplatin (90 mg/m2) given to 12 patients. Each dose of cisplatin induced transient increases in enzyme excretion, followed by proteinuria 3-5 days later. Transient enzymuria after the last cisplatin dose was significantly greater than that after the first dose. Moreover, persistent increases in urinary N-acetyl-beta-D-glucosaminidase and serum creatinine concentrations over pretherapy levels indicated chronic renal tubular damage. Our findings disclosed striking differences between patients in susceptibility to progressive nephrotoxicity.

Urinary excretion of alanine-aminopeptidase and N-acetyl-beta-D-glucosaminidase during sequential combination chemotherapy.

The urinary excretion of alanine aminopeptidase (EC 3.4.11.2) and N-acetyl-beta-D-glucosaminidase (EC 3.2.1.30) was determined in 23 patients with testicular cancer during sequential combination chemotherapy with vinblastine/bleomycin and doxorubicin/cis-platinum. Increases in enzyme excretion were more often noticed during therapy with vinblastine/bleomycin than with doxorubicin/cis-platinum. Moreover, the rises during vinblastine/bleomycin therapy were more pronounced. The enzyme activities varied from the normal range up to the 14-fold of the upper limit of the normal range. With few exceptions, enzyme excretions returned to normal or slightly elevated values before the subsequent course. No renal insufficiency could be detected with the commonly used parameters of renal function such as serum creatinine concentrations and creatinine clearance values, which were determined at irregular intervals.

Nephrotoxicity of radiocontrast media in ischemic renal failure in rabbits.

Ischemic renal failure was produced in rabbits by occluding the renal arteries for 90 min. Group 1 (n = 8) received radiocontrast media at the time of occlusion, group 2 (n = 8) 24 h after occlusion, and group 3 (n = 8) 3 days after occlusion. Group 4 (n = 12) was subjected to ischemic injury alone, group 5 (n = 4) served as sham-operated controls and group 6 (n = 4) did not undergo surgery but received radiocontrast media. Serum creatinine concentration in group 1 increased to a greater degree (p less than 0.001) than all other groups and did not return to normal during the 8-day observation period. Creatinine concentration in groups 2, 3, 4, and 6 were comparable and significantly increased compared to sham-operated group (p less than 0.05). Urinary excretion of alanine aminopeptidase and N-acetyl-beta-glucosaminidase in group 1 was significantly greater than all other groups (p less than 0.05). Microscopic analysis indicated tubular necrosis was more prominent in group 1. Radiocontrast media is nephrotoxic and in the setting of ischemic injury may prevent recovery of renal function. Toxicity was dependent on the time of administration since functional impairment was not increased if dye was given 1 or 3 days after ischemic injury.

Urinary excretion of [formula omitted] and alanine aminopeptidase in patients receiving amikacin or cis-platinum

Urinary excretion of alanine aminopeptidase (EC 3.4.11.2) and N- acetyl-β- D - glucosaminidase (EC 3.2.1.30) was determined for 25–70 days in five patients receiving cis-platinum and for 8–53 days in six patients receiving amikacin. This study was performed to investigate if the excretion of urinary enzymes represents a sensitive parameter for the early detection of toxic kidney damage. The determination of N- acetyl-β- d - glucosaminidase was carried out by the method of Knoll et al. [13]. The procedure of Mondorf et al. [14] for the estimation of alanine aminopeptidase activity was adapted to the Gemsaec Fast-Analyzer. In both patient groups an increase in the excretion of the two enzyme activities could be demonstrated. In patients receiving amikacin, the excretion of alanine aminopeptidase was always higher than that of N- acetyl-β- d - glucosaminidase , whereas in three patients receiving

ラット尿中L-Alanine aminopeptidase活性に見られる性差

ラット尿中L-Alanine aminopeptidase活性に見られる性差

Urinary excretion of alanine aminopeptidase and total proteinuria in experimental diabetes mellitus before and after islet transplantation.

Urinary excretion of alanine aminopeptidase and total proteinuria in experimental diabetes mellitus before and after islet transplantation.

Comparative studies on the action of aminoglycosides and cephalosporins on the proximal tubule of the human kidney

The urinary excretion of alanine aminopeptidase was measured in healthy volunteers, 59 receiving cephalosporins and 78 receiving aminoglycosides over a period of 3 days. A rise in excretion of the enzyme followed administration of cephacetrile 8.0 g daily but was not seen after 8.0 g cephalothin or 6.0 g doses of cefamandole or cephacetril. All the aminoglycosides tested produced a rise in enzyme excretion in the urine with amikacin (10 mg/kg/day), gentamicin (3 mg/kg/day) and sisomicin (3 mg/kg/day) producing higher mean MICs than seen with tobramycin (3 mg/kg/day) or netilmicin (3 mg/kg/day). The effect was shown to be dose-related in further studies with amikacin and netilmicin.