False positivity of gamma-glutamyl transpeptidase measurement in urine.

Although enzymuria tends to be associated to renal injury, there are no studies that have evaluated the presence of the enzyme gamma-glutamyl transpeptidase (GGT) spectrophotometry in the urine using a non-nephrotoxic agent (Nerium oleander) in order to evaluate the possibility of false positive results. The urinary GGT/urinary creatinine concentration ratio (uGGT/uCr) of 10 healthy dogs was calculated and posteriorly confronted with data from clinical evaluation, hematological and serum biochemical profiles, creatinine clearance (CrC), urinalysis, urine protein/creatinine ratio (UPC), electrocardiogram, systemic blood pressure (SBP) and light and electron microscopy. The results for kidney histology, SBP, UPC and CrC were not significantly different in any of the time-points analyzed. However, uGGT/uCr was significantly higher when measured 4 hours and 24 hours after administration of N. oleander. The measurement of the urinary GGT enzyme, as performed in many studies, yielded false positive results in dogs poisoned by a non-nephrotoxic agent.

The protective effects of the traditional Chinese herbs against renal damage induced by extracorporeal shock wave lithotripsy: a clinical study.

Extracorporeal shock wave lithotripsy (ESWL)-induced renal damage can occur as a result of multiple mechanisms. We have reported previously that Astragalus membranaceus, Salvia miltiorrhiza, a decoction of six drugs containing rhizoma Rehmanniae preparata and supplements of a few traditional Chinese medicinal herbs for invigorating the kidney and excreting calculus, have a protective effect on renal injury induced by high-energy shock waves (HESW) in rabbits. In this clinical study we further investigate the protective effects of these traditional Chinese herbs against renal damage induced by ESWL. Sixty consenting patients with renal calculus who underwent ESWL treatment were included and randomly assigned to the medication group or control group. Post-ESWL plasma nitric oxide (NO), endothelin-1 (ET-1), malondialdehyde (MDA), and serum tumor necrosis factor α (TNF-α) increased significantly in the controls (P < 0.05), while in the medication group, slightly but not significantly elevated levels of plasma ET-1, NO, and serum TNF-α were found. The difference between the groups was statistically significant (P < 0.05). The levels of superoxide dismutase (SOD) decreased gradually in the controls, reaching a trough 72 h after ESWL (P < 0.05), while in the treated group it was unchanged, and remained at a level higher versus the controls (P < 0.05). Plasma NO peaked twice by 72 h and at 1 week in the controls (P < 0.05). Urinary enzymes and ß(2)-microglobulin increased significantly and peaked by 24 h and immediately after ESWL (P < 0.05). These values were greater in the controls, and the difference was statistically significant (P < 0.05). This study demonstrates that the preparations of traditional Chinese medicines for invigorating the kidney and excreting calculus can reduce renal tubular damage induced by ESWL, and can shorten the recovery time of renal tubules in human subjects.

Attenuation of gentamicin-induced nephrotoxicity: trimetazidine versus N-acetyl cysteine.

Gentamicin (G) is a highly nephrotoxic aminoglucoside. It was used to experimentally induce nephrotoxicity in male Wistar rats. To find a drug capable of protecting the nephron we assayed a cardioprotector (trimetazidine, TMZ) and a hepatoprotector (N-acetyl cysteine, NAC). The rats were divided into six groups (n = 8): (A) control without drugs; (B) treated with 50 mg kg(-1) per day (i.p.) of G for 7 days; (C) diet supplemented with 20 mg kg(-1) per day of TMZ for 7 days; (D) treated with 10 mg kg(-1) per day (i.p.) of NAC for 7 days; (E) pretreated for 7 days with 20 mg kg(-1) per day of TMZ and during the following 7 days with G + TMZ; (F) pretreated for 7 days with 10 mg kg(-1) per day (i.p.) of NAC and during the following 7 days with G + NAC. Urea and creatinine as well as the excretion of urinary gamma-glutamyl transpeptidase (GGT(u)) and urinary N-acetyl-glucosaminidase (NAG(u)) were determined and structural and ultrastructural studies were carried out. Group B was used as a G-induced nephrotoxicity control. Pretreatment with TMZ (E) showed a protector effect against induced nephrotoxicity, with no biochemical or functional changes nor alterations in histoarchitecture or ultrastructure. Pretreatment with NAC (F) showed no protector effect against G-induced nephrotoxicity since no statistically significant differences were found with respect to the control group with G. We conclude that G-induced nephrotoxicity is attenuated by the cytoprotective effect of TMZ. We may infer that TMZ inhibits the reabsorption and consequently the accumulation of G in the proximal tubule cell.

[The protective effect of Chinese herbs for supplementing shen to eliminate stone on renal injury induced by extracorporeal shockwave lithotripsy in patients with renal calculus].

OBJECTIVE: To study the protective effect of Chinese herbs for supplementing Shen to eliminate stone on renal injury induced by extracorporeal shockwave lithotripsy (ESWL) in patients with renal calculus. METHODS: Sixty patients with diagnosis of renal calculus confirmed by X-ray film or CT combined with abdominal B ultrasonography but showing no obvious symptoms, were randomized into the treated group and the control group. They all were scheduled to receive ESWL treatment. To the patients in the treated group, prescribed Chinese herbs was orally administered in the three days before and after ESWL, patients in the control group ate and drank as usual. Changes of blood levels of nitric oxide (NO), endothelin-1 (ET-1), superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor alpha (TNF-alpha), urinary levels of N-acetyl-D-glucosaminidase (NAG), gamma-glutamyltransferase (gamma-GT) and beta 2-microglobulin (beta 2-MG) before and after ESWL were observed. RESULTS: Blood levels of NO, ET-1, MDA and TNF-alpha significantly increased after ESWL in the control group, higher than the levels in the treated group (P < 0.05); and level of SOD decreased gradually in the control group reaching the valley 72 h after ESWL (P < 0.05), while in the treated group it was unchanged and remained at the level higher than that in the control group (P < 0.05). As for the urinary levels of NAG, gamma-GT and beta2-MG, after ESWL, they were all higher in the control group than those in the treated group, showing statistical significance (P <0. 05). CONCLUSION: ESWL could induce renal damage in patients with renal calculus and the Chinese herbs for supplementing Shen to eliminate stone can reduce the renal tubular damage by way of anti-oxidation and regulating the renal hemorrheologic disorder and the release of inflammatory mediators.

[Effects of fractionated low dose Cisplatin on renal functions of patients with gastric carcinoma].

BACKGROUND & OBJECTIVE: Cisplatin (DDP) in large dosage impairs renal functions, while the impact of fractionated low dose DDP on renal functions is unclear. This study was to evaluate the effects of fractionated low dose DDP on renal functions of gastric cancer patients. METHODS: From Sep. 1998 to Jun. 2002, 31 gastric cancer patients were treated with LFEP regimen at School of Oncology of Peking University: intravenous administration of calcium folinate (CF, 150 mg/m(2)) at Day 1-3, 5-fluorouracil (5-FU, 500 mg/m(2)) at Day 1-5, epirubicin (EPI, 60 mg/m(2)) at Day 1, and DDP (20 mg/m(2)) at Day 1-3. Urine N-acetyl-beta-D-glucosaminidase (NAG), gamma-glutamyl transferase (gamma-GT) and routine urine test were assessed before chemotherapy and every other day during the 14-day chemotherapy; serum creatinine (sCr) and urea nitrogen (BUN) were assessed at the 7th day and 14th day during treatment. RESULTS: Of the 31 patients, 13 had normal renal functions before chemotherapy, while only 1 had normal renal functions after chemotherapy. Urine NAG and gamma-GT were changed significantly after chemotherapy: they were increased significantly on the 4th day and maintained higher than normal level for another 14 days thereafter. Meanwhile, no significant change in sCr and BUN were observed. CONCLUSION: Combined chemotherapy with fractionated low dose DDP still adversely affects renal functions of gastric cancer patients, however, the long-term effects need to be clarified.

[The nephrotoxicity in rats caused by Longdan Xiegan decoction].

OBJECTIVE: To observe the renal injury in rats induced by Longdan Xiegan decoction (LDXGD) containing different dosages Aristolochia manshriensis. METHOD: SD rats were divided into four groups at random, and were fed with three kinds of LDXGD 13, 14.5, 17.5 g x kg(-1) (containing respectively A. manshriensis 1.5, 3, 6 g x kg(-1)) and distilled water respectively for 12 weeks. Renal functional parameters on 4,8,12 w were determined and changes of histomorphology in rats on the end of experiment were observed. RESULT: The LDXGD containing low dose (1.5 g x kg(-1)) A. manshriensis did't induce significantly renal injury in rats during 12 weeks; the LDXGD containing midst dose(3 g x kg(-1)) A. manshriensis induced light damage of proximal convoluted tubule epithelial cells in rats during 12 weeks; the LDXGD containing high dose(6 g x kg(-1)) A. manshriensis induced significantly renal injury in rats after administed 4 weeks. Along with the lasting of administration, the degree of injury became more seriously. The main renal injury location was in proximal convoluted tubule. CONCLUSION: The renal toxicity of LDXGD is correlated with the dose of A. manshriensis and the time of administration. The LDXGD containing low dose A. manshriensis has relative security. However, the LDXGD containing high dose A. manshriensis can induce renal injury.

Kidney toxicity of ingested uranium from drinking water.

BACKGROUND: In experimental settings, uranium is toxic to kidneys, but effects on humans are unclear. Ingestion of water from drilled wells is a source of high uranium exposure in some populations. METHODS: Uranium exposure was measured in 95 men and 98 women aged 18 to 81 years who had used drinking water from drilled wells for an average of 16 years. Urinary N-acetyl-gamma-d-glucosaminidase, alkaline phosphatase, lactate dehydrogenase, gamma-glutamyltransferase, and glutathione-S-transferase; serum cystatin C; and urinary and serum calcium, phosphate, glucose, and creatinine were measured to evaluate possible toxic effects of uranium on kidney cells and renal function. In addition, supine blood pressure was measured. Associations between uranium exposure and the outcome variables were modeled by using linear regression with adjustment for age, sex, body mass index, smoking, and analgesic use. RESULTS: Median uranium concentration in drinking water was 25 microg/L (interquartile range, 5 to 148 microg/L; maximum, 1,500 microg/L). Indicators of cytotoxicity and kidney function did not show evidence of renal damage. No statistically significant associations with uranium in urine, water, hair, or toenails was found for 10 kidney toxicity indicators. Uranium exposure was associated with greater diastolic and systolic blood pressures, and cumulative uranium intake was associated with increased glucose excretion in urine. CONCLUSION: Continuous uranium intake from drinking water, even at relatively high exposures, was not found to have cytotoxic effects on kidneys in humans.

Effects of green tea on urinary stone formation: an in vivo and in vitro study.

PURPOSE: We evaluated whether epigallocatechin gallate (EGCG), a main constituent of green tea polyphenols, could protect against cellular toxicity by oxalate and whether green tea supplementation attenuates the development of nephrolithiasis in an animal model. MATERIALS AND METHODS: Cells of the NRK-52E line were incubated with different concentrations of oxalate with and without EGCG, and toxicity and malondialdehyde assays were done to investigate the cytotoxic effect of oxalate and the anti-oxalate effect of EGCG.. In a second series of experiments, male Sprague-Dawley rats were divided into three groups. Group 1 animals (controls) were fed regular chow and drank water ad libitum; group 2 animals were fed chow containing 3% sodium oxalate with the administration of gentamicin (40 mg/kg) and drank water ad libitum; group 3 animals were fed the same diet as group 2 with gentamicin administration and drank only green tea. Rats were killed 4 weeks later after a 24-hour urine collection, and the kidneys were removed for morphologic examination. RESULTS: As oxalate concentrations increased, the number of surviving cells decreased, and the formation of free radicals increased. The administration of EGCG inhibited free-radical production induced by oxalate. Green tea supplementation decreased the excretion of urinary oxalate and the activities of urinary gammaglutamyltranspeptidase and N-acetylglucosaminidase. The number of crystals within kidneys in group 3 was significantly lower than in group 2. CONCLUSIONS: Green tea has an inhibitory effect on urinary stone formation, and the antioxidative action of EGCG is considered to be involved.

Effects of selenium and zinc on renal oxidative stress and apoptosis induced by fluoride in rats.

OBJECTIVE: To study the effects of selenium and zinc on oxidative stress, apoptosis, and cell cycle changes in rat renal cells induced by fluoride. METHODS: Wistar rats were given distilled water containing sodium fluoride (50 mg/L NaF) and were gavaged with different doses of selenium-zinc preparation for six months. Four groups were used and each group had eight animals (four males and four females). Group one, sham-handled control; group two, 50 mg/L NaF; group three, 50 mg/L NaF with a low dose of selenium-zinc preparation (0.1 mg/kg Na2 SeO3 and 14.8 mg/kg ZnSO4 x 7H2O); and group four, 50 mg/L NaF with a high dose of selenium-zinc preparation (0.2 mg/kg Na2 SeO3 and 29.6 mg/kg ZnSO4 x 7H2O). The activities of serum glutathione peroxidase (GSH-Px), kidney superoxide dismutase (SOD), and the levels of malondialdehyde (MDA) and glutathione (GSH) in the kidney were measured to assess the oxidative stress. Kidney cell apoptosis and cell cycle were detected by flow cytometry. RESULTS: NaF at the dose of 50 mg/L increased excretion of fluoride in urine, promoted activity of urine gamma-glutamyl transpeptidase (gamma-GT), inhibited activity of serum GSH-PX and kidney SOD, reduce kidney GSH content, and increased kidney MDA. NaF at the dose of 50 mg/L also induced rat renal apoptosis, reduced the cell number of G2/M phase in cell cycle, and decreased DNA relative content significantly. Selenium and zinc inhibited effects of NaF on oxidative stress and apoptosis, promoted the cell number of G2/M phase in cell cycle, but failed to increase relative DNA content significantly. CONCLUSION: Sodium fluoride administered at the dose of 50 mg/L for six months induced oxidative stress and apoptosis, and changes the cell cycle in rat renal cells. Selenium and zinc antagonize oxidative stress, apoptosis, and cell cycle changes induced by excess fluoride.

Toxicity, pathophysiology and pathology in sheep following dosing of the nephrotoxic plant Nolletia gariepina (DC) Mattf.

Ingestion of the plant Nolletia gariepina was confirmed as the cause of acute mortalities in cattle in the Kuruman area of the Northern Cape Province of South Africa. The aim of this trial was to investigate the toxic effects of this plant with respect to clinical signs, pathophysiology and pathology using the sheep as a model. At dosages of 1.5 g dried, milled plant material/kg body mass there were no detectable abnormal findings, while at dosages of 2.8-3.0 g/kg most of the animals died acutely. In subacutely affected sheep, depression, inappetance, teeth grinding, tachycardia, weak ruminal movements and recumbency were noticed. The most prominent pathophysiological changes observed, included a sharp rise in non-protein nitrogen substances in the plasma, remarkable decline in glomerular filtration rate, increase in sodium and potassium excretion, and a rise in urine gamma glutamyltransferase activity. Macroscopically a severe nephrosis was present in all the animals. The most important findings detected histologically were necrosis of the proximal convoluted tubular epithelium and large numbers of protein casts in the lumens.

Clinicopathological features in ovine AA amyloidosis.

This paper describes the clinicopathological findings in sheep with AA amyloidosis. Serum samples from 12 AA amyloid-affected sheep and urine samples from 5 of these ewes were analyzed. In sera, the most important alteration was reflected in hypoalbuminemia, high concentration in beta and gamma-globulins and high levels of serum BUN, phosphorous and potassium. Serum creatinine, cholesterol and calcium concentrations showed no alterations. Urinary analysis showed proteinuria and a high protein/creatinine ratio. In three urine samples, high activities of urinary enzymes gamma-glutamyl transferase (GGT), beta-glucuronidase (GRS) and N-acetyl-beta-D-glucosaminidase (NAG) were observed, their ratios with urinary creatinine being increased for GGT and NAG and decreased for GRS. In conclusion, important alterations in biochemical and urinary parameters were observed in ovine affected by systemic AA amyloidosis. Those related to the activities of urinary enzymes could constitute reliable parameters for assessing renal injury in ovine AA amyloidosis.

Renoprotective role of nifedipine during gentamicin therapy: randomized controlled trial.

AIM: To investigate the protective effect of nifedipine, a dihydropyridine calcium-channel blocker, on renal function (glomerular and tubular) in patients treated with gentamicin, an aminoglycoside antibiotic. METHODS: Thirty-two patients with gentamicin sensitive upper urinary tract infection have been screened and randomized to two groups. The placebo group was given gentamicin and placebo, and the intervention group gentamicin and nifedipine. Gentamicin was given in slow intravenous injection every 12 hours for 10 days, and nifedipine 10 mg orally, 3 times a day. RESULTS: Nifedipine administration during gentamicin therapy promoted primarily the glomerular filtration. In 62% of the patients treated with nifedipine creatinine clearance increased significantly by the end of the study. In the placebo group, 69% of the patients had a creatinine clearance significantly below the baseline at the end of the study. The decrease in creatinine clearance by more than 50% from the initial values was found in 2 patients (1 in each group). There was a significant increase in gammaGT/creatinine clearance ratio in both groups at the end of therapy, indicating that nifedipine did not prevent the brush-border membranous enzyme release caused by gentamicin. CONCLUSION: Nifedipine has positive effects on renal hemodynamics in patients treated with gentamicin. Most likely, the mechanism of action is an increase in glomerular filtration caused by preglomerular vasodilatation.

Protective effect of oral L-arginine administration on gentamicin-induced renal failure in rats.

We investigated the effects of orally supplemented L-arginine, the substrate of nitric oxide (NO) and N(omega)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide-synthase inhibitor in gentamicin-induced renal failure. Rats were given gentamicin (100 mg/kg/day s.c.), gentamicin and L-arginine (2 g/l, drinking water), gentamicin and L-NAME (100 mg/l, drinking water) or gentamicin plus L-arginine and L-NAME. After 8 days, the gentamicin group developed marked renal failure, characterized by a significantly decreased creatinine clearance and increased blood creatinine, fractional excretion of sodium, fractional excretion of lithium, urine gamma glutamyl transferase, systolic blood pressure and daily urine volume when compared to controls. Renal histological analysis confirmed tubular necrosis. L-arginine administration caused normalization of these parameters, whereas L-NAME led to aggravation of the failure. Concomitant administration of L-NAME and L-arginine to gentamicin-treated rats caused no significant changes when compared to the rats receiving gentamicin alone. We conclude that L-arginine supplementation has beneficial effects in gentamicin-induced renal failure in rats and that these effects are reversed by the NO-synthase inhibitor, L-NAME.

Vitamin E pretreatment prevents cyclosporin A-induced crystal deposition in hyperoxaluric rats.

The in vivo effect of cyclosporin A (CsA) on renal calcium oxalate (CaOx) crystal retention in experimental hyperoxaluric rats was investigated. Further, the effect of pretreatment of vitamin E on the above conditions was also studied. Male Wistar rats were divided into two major groups each containing 40 rats. One of the groups was pretreated with vitamin E. Both major groups were then subgrouped into four groups: group 1 received the vehicle (olive oil); group 2 received CsA in olive oil (50 mg/kg); group 3 received 3% ammonium oxalate (AmOx), and group 4 received CsA + AmOx. Nephrotoxicity was assessed by the activities of urinary marker enzymes and also by histopathology. Urinary oxalate excretion as well as the activities of lactate dehydrogenase, gamma-glutamyltranspeptidase, alkaline phosphatase and inorganic pyrophosphatase enzymes were elevated either in CsA-alone or AmOx-alone treated groups. On combined administration of both CsA and AmOx, further elevations of these enzymes were observed. Urinary excretion of oxalate concentration positively correlated with urinary excretion of these enzymes. Deposition of CaOx crystals was seen only in the kidneys of rats that received combined treatment. On pretreatment with vitamin E the observed increased urinary activities of the enzymes and oxalate, histopathological changes and the deposition of CaOx crystals by administration of CsA in hyperoxaluria were prevented suggesting that vitamin E could be supplemented to prevent CsA-induced membrane damage.

Alterations in some risk factors and urinary enzymes in urolithiatic rats treated with sodium pentosan polysulphate.

The effect of sodium pentosan polysulphate (SPP) was investigated in calcium oxalate stone forming rats with respect to the urinary excretion of certain risk factors and enzymes. Calcium oxalate stones were induced by feeding 3% w/w sodium glycollate to the rats. Urinary calcium, oxalate, phosphorus and uric acid levels were increased in stone formers. In contrast magnesium excretion was low in this group. SPP treatment lowered oxalate and calcium levels in both controls and experimental animals. Magnesium levels were increased moderately. Increased excretion of urinary enzymes--LDH, alkaline phosphatase, gamma-GT and beta glucuronidase--in calculogenic rats indicates membranuria and damage to proximal tubules during stone formation. Decreased pyrophosphatase activity was observed in glycollate fed rats. SPP treatment decreased the excretion of the above enzymes in the treated groups. Stone formers exhibited decreased LAP and fibrinolytic (urokinase) activities. SPP being associated with fibrinolytic properties, increased the activities of the above two enzymes to that of control levels in calculogenic rats.

Effects of acute and sub-chronic administration of iron nitrilotriacetate in the rat.

Parenteral administration of iron nitrilotriacetate (FeNTA) to rats resulted in marked loss in body weight, and increases in liver/and kidney/body weight ratios. Fatalities, due to renal failure, depended on dosage and age of the animals, and were greater (70%) after a single large dose (12 mg iron) than after repeated smaller doses (30%). FeNTA administered subchronically gave rise to an increase in ethane exhalation, and to decreased liver glutathione peroxidase activity, and decreased cytochrome P-450 concentration and benzphetamine N-demethylase activity. It also resulted in severe renal tubular necrosis, with deposition of iron in the tubular cells and loss of brush border alkaline phosphatase activity, resulting in a dose-dependent diuresis, with increased urinary excretion of glucose, iron and lipid peroxidation products, and decreased urine creatinine concentration. NTA alone had none of these effects but slightly decreased the hepatic concentration of iron.

Renal toxicity of aminoglycosides in the neonatal period.

Renal toxicity of aminoglycosides seems to be less frequent in newborn infants compared to adults even though glomerular filtration rate and tubular secretion and reabsorption mechanisms are subjected to adaptive processes during the neonatal period. In 14 infants, kinetic parameters of gentamicin were determined using an open three-compartment body model. According to the lower glomerular filtration rate, the beta-elimination phase is longer in the newborn infant compared to adults, while the gamma-elimination phase is quite similar to adult values. The calculated drug accumulation in the deep compartment (kidney) under steady-state conditions is lower in newborns compared to infants. The excretion of urinary enzymes of tubular origin, that is the lysosomal NAG (N-acetyl-beta-D-glucosaminidase), beta-glucuronidase, and the brush-border-associated AAP (alanine-aminopeptidase), GGT (gamma-glutamyl-transpeptidase), are lower in healthy newborn infants compared to older ones. The increase of AAP, for instance, during aminoglycoside therapy is less pronounced in newborn infants, especially in prematures, if compared to adult values. After end of therapy the AAP excretion decreases to normal. The calculated rate of this decrease takes place in a fashion similar to the release of drugs from the kidney (gamma-elimination phase). The data indicate that there may be a lower renal accumulation of aminoglycosides in newborn infants, which can be explained by the morphometric and functional characteristics of the newborn kidney.

[Protection against mercuric chloride nephropathy by sodium selenite in the rat]. / Protection de la néphropathie au chlorure mercurique par le sélénite de sodium chez le rat.

Daily intraperitoneal injection of 2.5 or 5 mumole HgCl2 to male Rats weighing 250 to 350 g induces an early intense increase of urine gamma-glutamyl transferase activity. In the same conditions, equimolecular administration of sodium selenite and mercuric chloride induces no increase of the enzymuria for the low dose: for the high dose- a minor and more persistent increase of urine GGT is observed. Thus, the activity of urines GGT allows, in vivo, to establish that sodium selenite protects Rat kidney against toxic effects of mercuric chloride.

Urine gamma-glutamyl transferase in rat kidney toxicology: nephropathy by repeated injections of mercuric chloride. Effects of sodium selenite.

Groups of 5 male and 4 female Cobs CD rats weighing 250--350 g were injected intraperitoneally, daily for 15 days, with 5 mumol HgCl2/kg, 5 mumol Na2SeO3/kg, or (5 mumol HgCl2 + 5 mumol Na2SeO3)/kg in a 10 ml/kg vol. of saline. Control animals were injected with saline only. Injection of saline or sodium selenite produced neither modification of diuresis, nor of urine elimination of sodium, potassium, chloride, phosphates, urea, creatinine and gamma-glutamyl transferase (GGT). Injection of mercuric chloride induced a massive increase of urine GGT, diuresis and phosphaturia and a decrease of kaliuria and natriuria. Those effects reflect a kidney tubular lesion which seems to be more severe in males than in females. Injection of mixed sodium selenite and mercuric chloride or separate injection of both compounds had similar effects. In both sexes, urine GGT elimination was delayed and about 2 times lower than with HgCl2 alone. In females, the other urine parameters were almost normal whereas in males, diuresis and phosphaturia were slightly increased and kaliuria decreased. The observation of urine GGT elimination attests, in vivo, that sodium selenite decreases tubular toxicity of mercuric chloride and resulting kidney function disturbances.

[The influence of vitamin a, gentamicin and anoxaemia on urinary enzyme excretion (author's transl)]. / Verhalten von Harnenzymen nach Vitamin A, Gentamycin und Klemmung der Nierenarterien

The excretion patterns of several urinary enzymes were investigated in the following four experimental groups of Wistar rats and compared with the normal range of each urinary enzyme studied. One group received vitamin A in high dosage; a second group was given vitamin A before and after bilateral clamping of the renal artery for 30 minutes; in the third group the renal arteries were clamped for 30 or 60 minutes; the last group of experimental animals received first low (2mg/kg, 4mg/kg) and subsequently high doses (100 mg/kg) of gentamicin. Vitamin A administration produced no increase in urinary enzyme activity, even in the group of rats with ischaemically-damaged kidneys, where ischaemia (clampin of the arteries) was responsible per se for an increase in enzyme excretion. With low doses of gentamicin the urinary enzymes remained within normal limits, but increased immediately to significantly pathological values after the first dose 100 mg/kg gentamicin.