Induction of nephrotoxicity by high doses of gentamicin in diabetic rats

Rats with streptozotocin-induced diabetes mellitus (DM) are resistant to aminoglycoside (AG) nephrotoxicity presumably because of defective transport and accumulation of drug by proximal tubular cells. To test this hypothesis we injected DM rats with saline or with gentamicin, 100, 200, and 400 mg/kg per day for 6 days, to determine if the renal cortical concentration of gentamicin could be raised to toxic levels. Nephrotoxicity was assessed by monitoring for evidence of accelerated lipid peroxidation in the renal cortex, for elevation of the serum creatinine concentration, and for evidence of proximal tubular cell injury and necrosis by light and electron microscopy. At 100 mg/kg per day renal cortical gentamicin was 454 +/- 85 micrograms/g. Except for an increase in renal cortical phospholipids these rats manifested no evidence of accelerated lipid peroxidation or elevation of serum creatinine. At 200 mg/kg per day renal cortical gentamicin rose to 636 +/- 20 micrograms/g. These rats manifested mild functional and morphological evidence of toxicity. At 400 mg/kg renal cortical gentamicin rose to 741 +/- 43 micrograms/g. These rats developed severe nephrotoxic injury as manifested by a marked increase of lipid peroxidation evident by an increase of malondialdehyde from a control level of 0.48 +/- 0.02 to 1.72 +/- 0.12 nmole/mg protein, a shift from unsaturated to saturated fatty acids esterified in renal cortical phospholipids, depression of superoxide dismutase and catalase, and a shift from reduced to oxidized glutathione. The serum creatinine rose from a baseline level of 0.24 +/- 0.01 to 0.46 +/- 0.05 mg/dl. Light and electron microscopy revealed enlarged lysosomes distended with typical myeloid bodies and extensive proximal tubular cell necrosis. These observations provide compelling evidence in support of the view that the resistance of DM rats to AG nephrotoxicity is causally linked to the low rate of drug uptake by renal proximal tubular cells. When the renal cortical concentration reaches a critical level, it elicits a pattern of toxic injury indistinguishable from that of nondiabetic rats. Thus, there is nothing inherent to the diabetic state that prevents AGs from causing their usual adverse effects on the metabolism of renal proximal tubular cells once they gain access in sufficient quantity into these cells.     

Nephroprotective effect of pigmented violacein isolated from Chromobacterium violaceum in wistar rats

The present study aimed to analyze the nephroprotective property of violacein obtained from the bacterium, Chromobacterium violaceum. The nephrotoxicity in the animal model was induced by gentamicin, potassium dichromate, mercuric chloride, and cadmium chloride-induced nephrotoxicity in the Wistar rats was analyzed by measuring the serum creatinine, uric acid, and urea level. The present investigation revealed the nephroprotective property on convoluted proximal tubule (S1 and S2 segments) and the straight proximal tubule (S3 segment). Also, violacein significantly improved the renal function by the renal protective property on S2 segment of proximal tubule from the nephrotoxicity stimulated by mercuric chloride, potassium dichromate, cadmium chloride and gentamicin in animal models. Animal model studies revealed that violacein at 20 and 40 mg/kg p.o improved the renal function and significantly reduced the increased amount of uric acid, creatinine, and blood urea compared to the control.     

Carvedilol: a beta blocker with antioxidant property protects against gentamicin-induced nephrotoxicity in rats

Gentamicin is an antibiotic effective against gram negative infections, whose clinical use is limited by its nephrotoxicity. Since the pathogenesis of gentamicin-induced nephrotoxicity involves oxygen free radicals, the antioxidant carvedilol may protect against gentamicin-induced renal toxicity. We therefore tested this hypothesis using a rat model of gentamicin nephrotoxicity. Carvedilol (2 mg/kg) was administered intraperitoneally 3 days before and 8 days concurrently with gentamicin (80 mg/kg BW). Estimations of urine creatinine, glucose, blood urea, serum creatinine, plasma and kidney tissue malondialdehyde (MDA) were carried out, after the last dose of gentamicin. Kidneys were also examined for morphological changes. Gentamicin caused marked nephrotoxicity as evidenced by increase in blood urea, serum creatinine and decreased in creatinine clearance. Blood urea and serum creatinine was increased by 883% and 480% respectively with gentamicin compared to control. Carvedilol protected the rats from gentamicin induced nephrotoxicity. Rise in blood urea, serum creatinine and decrease in creatinine clearance was significantly prevented by carvedilol. There was 190% and 377% rise in plasma and kidney tissue MDA with gentamicin. Carvedilol prevented the gentamicin induced rise in both plasma and kidney tissue MDA. Kidney from gentamicin treated rats, histologically showed necrosis and desquamation of tubular epithelial cells in renal cortex, whereas it was very much comparable to control with carvedilol. In conclusion, carvedilol with its antioxidant property protected the rats from gentamicin-induced nephrotoxicity.     

Effect of crocus sativus on gentamicin induced nephrotoxicity

Crocus sativus, known as saffron, is used in folk medicine for treatment of different types of diseases, and its anti-inflammatory and free radical scavenging activities have been demonstrated. The present study evaluated gentamicin nephrotoxicity in saffron treated rats. Male Wistar rats (200-250 g) were treated with saffron (40 or 80 mg/k/d) for 10 days, or saffron (40 or 80 mg/ kg/d) for 10 days and gentamicin 80 mg/kg/d for five days, starting from day 6. At the end of treatment, blood samples were taken for measurement of serum creatinine (SCr) and BUN. The left kidney was prepared for histological evaluation and the right kidney for Malondialdehyde (MDA) measurement. Gentamicin 80 (mg/k/d) increased SCr, BUN and renal tissue levels of MDA and induced severe histological changes. Saffron at 40 mg/k/d significantly reduced gentamicin-induced increases in BUN and histological scores (p<0.05). Gentamicin-induced increases in BUN, SCr and MDA and histological injury were significantly reduced by treatment with saffron 80 mg/k/d (p<0.05, p<0.001, p<0.05, and p<0.001 respectively). In conclusion, our results suggest that saffron treatment reduces gentamicin-induced nephrotoxicity and this effect seems to be dose dependent.     

Protective effect of Panax ginseng against serum biochemical changes and apoptosis in kidney of rats treated with gentamicin sulphate

The protective effects of Panax ginseng (PG) on gentamicin sulphate (GS) induced acute nephrotoxicity were investigated in rats. A total of 32 adult Sprague-Dawley rats were randomly divided into 4 equal groups and treated by intraperitoneous route for 10?days with: 0.5?mL of isotonic saline (group C), GS 100?mg/kg/day (group GS), co treatment PG (100 and 200?mg/kg/day) plus GS (100?mg/kg/day). After the last injection, kidney markers (urea, creatinine and blood urea nitrogen-BUN) and hepatic markers (aspartate aminotransferase-AST, alanine aminotransferase-ALT, gama glutamil transferase-GGT), and biochemical parameters were analyzed using diagnostic kits. Also, kidney changes were evaluated by immunohistochemical and stereological methods. GS treatment induced significant elevation (P?相似文献   

Protective effect of aminoguanidine against nephrotoxicity induced by cisplatin in normal rats

The effect of aminoguanidine (AG) on nephrotoxicity induced by cisplatin (CDDP) was investigated. A single dose of CDDP (7.5 mg/kg i.p.) induced nephrotoxicity, manifested biochemically by a significant elevation in serum urea, creatinine and a severe decrease in serum albumin. Moreover, marked increases in kidney weight, urine volume and urinary excretion of albumin were observed. Nephrotoxicity was further confirmed by a significant decrease in glutathione-S-transferase (GST, E.C. 2.5.1.18), glutathione peroxidase (GSH-Px, E.C. 1.11.1.9) and catalase (E.C. 1.11.1.6) and a significant increase in lipid peroxides measured as malondialdhyde (MDA) in kidney homogenates. Administration of AG (100 mg/kg per day p.o.) in drinking water 5 days before and 5 days after CDDP injection produced a significant protection against nephrotoxicity induced by CDDP. The amelioration of nephrotoxicity was evidenced by significant reductions in serum urea and creatinine concentrations. In addition, AG tended to normalize decreased levels of serum albumin. Urine volume, urinary excretions of albumin and GST and kidney weight were significantly decreased. Moreover, AG prevented the rise of MDA and the reduction of GST and GSH-Px activities in the kidney. These results suggest that AG has a protective effect on nephrotoxicity induced by CDDP and it may therefore improve the therapeutic index of CDDP.     

Adaptation to nephrotoxic chemicals

Rats given gentamicin chronically become resistant to its nephrotoxic effects. To further explore this adaptation to nephrotoxicity, we gave male rats gentamicin 40 mg/kg/day for 12 days, then 80 mg/kg/day for 24 days. We then challenged them with 110 mg/kg/day of gentamicin for 9 days. Spermine was given 16 mg/kg/day for 42 days, then gentamicin challenge at 60 mg/kg/day for 9 days. Gossypol was given at 6 mg/kg/day for 19 days, then gentamicin at 60 mg/kg/day for 21 days. A fourth group of rats (controls) received 0.5 ml saline daily for 42 days and then received gentamicin 60 mg/kg/day for 9 days. Urine N-acetyl-beta-glucosaminidase (NAG) was measured 3 times weekly and serum creatinine was measured 5 times during the study. Each drug-treated rat increased its urine NAG from baseline values. After a period of drug administration, all NAG values returned to the predrug values. Then all animals were given gentamicin daily. NAG values increased 20-fold in the animals previously treated with saline but did not rise in the other groups. The serum creatinine frequently but not always changed in parallel with the NAG values. These observations indicate that adaptation to these nephrotoxic substances occurs and that cross-resistance to gentamicin is produced by spermine and gossypol.     

Therapeutic effect of ethanolic extract of Hygrophila spinosa T. Anders on gentamicin-induced nephrotoxicity in rats

Therapeutic effect of ethanolic extract of Hygrophila spinosa in gentamicin-induced nephrotoxic model of kidney injury in male Sprague-Dawley rats was studied. Rats were administered with gentamicin at a dose of 80 mg/kg intraperitoneally (ip) to induce nephrotoxicity. Kidney function was assessed by measuring serum creatinine and urea. Kidney superoxide dismutase, lipid peroxidation, catalase and reduced glutathione were also measured in control and treated rats. H. spinosa extract showed free radical scavenging activities at doses of 50 and 250 mg/kg with a predominant activity at 250 mg/kg. The ethanolic extract also caused a reduction in serum creatinine and urea levels. Histopathological studies were conducted to confirm the therapeutic action of the plant extract. The results demonstrated that the ethanolic extract of whole plant of H. spinosa evinced the therapeutic effect and inhibited gentamicin-induced proximal tubular necrosis.     

Mechanism-Based Urinary Biomarkers to Identify the Potential for Aminoglycoside-Induced Nephrotoxicity in Premature Neonates: A Proof-of-Concept Study

Premature infants are frequently exposed to aminoglycoside antibiotics. Novel urinary biomarkers may provide a non-invasive means for the early identification of aminoglycoside-related proximal tubule renal toxicity, to enable adjustment of treatment and identification of infants at risk of long-term renal impairment. In this proof-of-concept study, urine samples were collected from 41 premature neonates (≤32 weeks gestation) at least once per week, and daily during courses of gentamicin, and for 3 days afterwards. Significant increases were observed in the three urinary biomarkers measured (Kidney Injury Molecule-1 (KIM-1), Neutrophil Gelatinase-associated Lipocalin (NGAL), and N-acetyl-β-D-glucosaminidase (NAG)) during treatment with multiple courses of gentamicin. When adjusted for potential confounders, the treatment effect of gentamicin remained significant only for KIM-1 (mean difference from not treated, 1.35 ng/mg urinary creatinine; 95% CI 0.05-2.65). Our study shows that (a) it is possible to collect serial urine samples from premature neonates, and that (b) proximal tubule specific urinary biomarkers can act as indicators of aminoglycoside-associated nephrotoxicity in this age group. Further studies to investigate the clinical utility of novel urinary biomarkers in comparison to serum creatinine need to be undertaken.     

Effect of oral administration of Arabic gum on cisplatin-induced nephrotoxicity in rats

It has been recently postulated from our laboratory that Arabic gum (AG) offers a protective effect in the kidney of rats against nephrotoxicity induced by gentamicin via inhibiting lipid peroxidation. It has also recently shown a powerful antioxidant effect through scavenging superoxide anions. In this study we utilized a rat model of cisplatin (CP)-induced nephrotoxicity to determine its peak time following (1, 2, 5, and 7 days) of a single CP (7.5 mg/kg, i.p.) injection. Also, a possible protective effect of cotreatment with AG (7.5 g/kg/day p.o.) on CP-induced nephrotoxicity was investigated. Biochemical as well as histological assessments were carried out. CP-induced nephrotoxicity was manifested by significant elevations of the functional parameters blood urea, serum creatinine, and kidney/body weight ratio. Maximum toxic effects of CP were observed 5 days after its injection, while it started after day 1 in the biochemical parameters, such as glutathione depletion in the kidney tissue with concomitant increases in lipid peroxides and platinum content. Additionally, severe necrosis and desquamation of tubular epithelial cells in renal cortex as well as interstitial nephritis were observed after 5 days in CP-treated animals. Five days after AG cotreatment with CP did not protect the kidney from the damaging effects of CP. However, it significantly reduced CP-induced lipid peroxidation. These findings suggest that lipid peroxidation is not the main cause of CP-induced nephrotoxicity but it is rather more dependent on other factors such as platinum disposition in renal interstitial tubules.     

Alpha lipoic acid prevents doxorubicin‐induced nephrotoxicity by mitigation of oxidative stress,inflammation, and apoptosis in rats

This study aimed to evaluate the protective effects of alpha lipoic acid (ALA) against doxorubicin (DOX)‐induced nephrotoxicity in rats. A single dose of DOX (7.5 mg/kg i.v.) induced nephrotoxicity evidenced by significant elevations in kidney weight, kidney/body weight ratio, serum urea, creatinine, tumor necrosis factor alpha, and renal contents of malondialdehyde, nitric oxide, cyclooxygenase‐2, and caspase‐3. Also, it causes significant reduction in final body weight, serum albumin, renal contents of reduced glutathione and superoxide dismutase activity. Histopathological changes in the kidney tissue confirmed the nephrotoxic effect. In contrast, pretreatment with ALA (50 mg/kg, orally) for 14 days before DOX and for 7 days after DOX administration mitigated renal toxicity evidenced by greater improvement in the examined oxidative stress, inflammation, and apoptosis parameters. In conclusion, ALA had promising protective effects against DOX‐induced nephrotoxicity that might be attributed to its antioxidant, anti‐inflammatory, and antiapoptoic activities.     

Ginkgo biloba extract ameliorates gentamicin-induced nephrotoxicity in rats.

The effect of Ginkgo biloba (EGb), a plant extract with an antioxidant effect, has been studied on gentamicin-induced nephrotoxicity in male wistar rats. Ginkgo biloba extract (300 mg/kg BW) was administered orally 2 days before and 8 days concurrently with gentamicin (80 mg/kg BW). Saline treated animals served as control. Estimations of urine creatinine, glucose, blood urea, serum creatinine, plasma and kidney tissue MDA were carried out after 8 days of gentamicin treatment. Kidneys were examined using histological techniques. Blood urea and serum creatinine were increased by 896% and 461% respectively, with gentamicin, compared to saline treated group. Creatinine clearance was significantly decreased with gentamicin. Ginkgo biloba extract protected rats from gentamicin-induced nephrotoxicity. Changes in blood urea, serum creatinine and creatinine clearance induced by gentamicin were significantly prevented by Ginkgo biloba extract. There was a 177% and 374% rise in plasma and kidney tissue MDA with gentamicin, which were significantly reduced to normal with Ginkgo biloba extract. Histomorphology showed necrosis and desquamation of tubular epithelial cells in renal cortex with gentamicin, while it was normal and comparable to control with Ginkgo biloba extract. These data suggest that supplementation of Ginkgo biloba extract may be helpful to reduce gentamicin nephrotoxicity.     

Protective effects of caffeic acid phenethyl ester (CAPE) on amikacin-induced nephrotoxicity in rats

Amikacin (AK) has nephrotoxic side effects. AK-induced nephrotoxicity may be the consequence of oxidative stress and so anti-oxidant agents could be useful in reducing AK toxicity. Caffeic acid phenethyl ester (CAPE) was recently shown to have free radical scavenging ability and it reduces lipid peroxidation. For this purpose, the rats were distributed into three groups: (I) injected with vehicle (control); (II) injected (i.p.) with 1.2 g kg(-1) AK at a single dose; (III) injected (i.p.) with AK plus 10 micromol kg(-1) CAPE. Renal morphology was investigated by light microscopy. Tissue samples and trunk blood were also obtained to determine renal malondialdehyde (MDA), blood urea nitrogen (BUN) and creatinine (Cr) levels. MDA production was found to be higher in rats given AK than among control rats. CAPE administration before AK injection caused a significant decrease in MDA production. Morphological tubule damage in rats given AK was severe in the renal cortex, whereas in rats given AK plus CAPE, no histological changes occurred. It is concluded that CAPE could be useful for reducing the nephrotoxic effects of AK. Copyright (c) 2005 John Wiley & Sons, Ltd.     

Inhibition of vancomycin-induced nephrotoxicity by targeting superoxide dismutase to renal proximal tubule cells in the rat

Vancomycin, a glycopeptide antibiotic, has a broad spectrum against methicillin-resistant Staphylococcus aureus (MRSA). Because vancomycin induces renal dysfunction, the dose and the duration of its administration are limited. The mechanism of vancomycin-induced renal dysfunction is not known. We recently synthesized a hexamethylenediamine-conjugated cationic superoxide dismutase (AH-SOD) which rapidly accumulates in renal proximal tubule cells and inhibits oxidative injury of the kidney. The present work reports the protective effects of AH-SOD against vancomycin-induced renal dysfunction. Male Wistar rats (200-210 g) were intraperitoneally administered with either 200 or 400 mg/kg of vancomycin twice a day for 7 days. Either 5 mg/kg/day AH-SOD or saline was subcutaneously injected 5 min before every vancomycin injection. Biochemical analysis revealed that plasma levels of blood urea nitrogen and creatinine increased significantly in vancomycin-treated group by an AH-SOD-inhibitable mechanism. Histological examination revealed that vancomycin also elicited a marked destruction of glomeruli and necrosis of proximal tubule by an AH-SOD inhibitable mechanism. These results suggest that oxidative stress underlies the pathogenesis of vancomycin-induced nephrotoxicity and that targeting SOD and/or related antioxidants to renal proximal tubule cells might permit the administration of higher doses of vancomycin sufficient for eradication of MRSA without causing renal injury.     

Effect of rosmarinic acid on inhibition of gentamicin induced nephrotoxicity in rats

The present investigation reports the effect of rosmarinic acid (RA), an antioxidant on gentamicin sulphate (GS)-induced renal oxidative damage in rats. Rosmarinic acid (RA) has been demonstrated to have antioxidant, free radical scavenger and anti-inflamatory effects. Twenty-eight Sprague-Dawley rats were divided in to four equal groups as follows: group 1 (control), group 2 (GS 100 mg/kg/d ip), group 3 (GS 100 mg/kg/d ip + RA 50 mg/kg/d) and group 4 (GS 100 mg/kg/d ip + RA 100 mg/kg/d). Treatments were administrated once daily for 12 days. After 12 days 24 h urine was collected, blood was sampled and kidneys were removed. Serum and kidney tissue MDA assessed by thiobarbituric acid. Kidney paraffin sections (5 μm thickness) from the left kidney stained with periodic acid Schiff. Tubular necrosis was studied semiquantitatively and glomerular volume and volume density of proximal convoluted tubule (PCT) estimated stereologically. Kidney homogenize were prepared from right kidney. Serum creatinine, urea and kidney antioxidant enzymes activity were assessed by special kits. Data were compared by SPSS 13 software and Mann–Whitney test at p < 0.05. Co treatment of GS and RA (High dose) significantly decreased serum creatinine, MDA, urea, tubular necrosis (p < 0.05) and increase renal GSH, GPX, CAT, SOD, volume density of PCT and creatinine clearance significantly in comparison with GS group (p < 0.05). Treatment with RA (high dose) maintained serum creatinine, volume density of PCT, renal GSH, GPX, SOD and MDA as the same level as control group significantly (p < 0.05). In conclusion, RA alleviates GS nephrotoxicity via antioxidant activity, increase of renal GSH content and increase of renal antioxidant enzymes activity.     

Cyclophosphamide-induced nephrotoxicity, genotoxicity, and damage in kidney genomic DNA of Swiss albino mice: the protective effect of Ellagic acid

Cyclophosphamide (CPM), an alkylating agent is used as an immunosuppressant in rheumatoid arthritis and in the treatment of several cancers as well. In this study, Ellagic acid (EA), a naturally occurring plant polyphenol, was evaluated for its antigenotoxicity and antioxidant efficacy against the CPM-induced renal oxidative stress and genotoxicity in Swiss albino mice. The mice were given a prophylactic treatment of EA orally at a dose of 50 and 100 mg/kg body weight (b wt) for seven consecutive days before the administration of a single intraperitoneal (i.p.) injection of CPM at 50 mg/kg b wt. The modulatory effects of EA on CPM-induced nephrotoxicity and genotoxicity were investigated by assaying oxidative stress biomarkers, serum kidney toxicity markers, DNA fragmentation, alkaline unwinding assay, micronuclei (MN) assay, and by histopathological examination of kidney tissue. A single intraperitoneal administration of CPM in mice increased malondialdehyde level with depletion in glutathione content, antioxidant enzymes activities, viz. glutathione peroxidase, glutathione reductase, catalase, quinone reductase, induced DNA strand breaks, and MN induction. EA oral administration at both doses caused significant reduction in their levels, restoration in the activities of antioxidant enzymes, reduction in MN formation, and DNA fragmentation. Serum toxicity marker enzymes like BUN, creatinine, and LDH were also increased after CPM treatment which was significantly decreased in EA pretreated groups. Present findings suggest a prominent role of EA against CPM-induced renal injury, DNA damage, and genotoxicity.     

Effect of platelet activating factor antagonist treatment on gentamicin nephrotoxicity

To assess whether PAF could be involved in the gentamicin-induced nephrotoxicity, we have studied the effect of PAF antagonist BN-52021 on renal function in rats after gentamicin (GENTA) treatment. Experiments were completed in 21 Wistar rats divided into three groups: group GENTA was injected with gentamicin 100 mg kg(-1) body wt/day s.c. for 6 days. Group GENTA + BN received gentamicin and BN-52021 i.p. 5 mg kg(-1) body wt/day. A third group served as control. Rats were placed in meta-bolic cages and plasma creatinine and creatinine clearance were measured daily. GENTA group showed a progressive increase in plasma creatinine, a drop in creatinine clearance and an increase in urinary excretion of N-acetyl-beta-D-glucosaminidase and alkaline phosphatase. GENTA + BN group showed a lesser change in plasma creatinine and a creatinine clearance, but no difference with GENTA group in urinary excretion of NAG and AP were observed. Histological examination revealed a massive cortical tubular necrosis in rats treated with gentamicin, whereas in BN-52021 injected animals tubular damage was markedly attenuated. The present results suggest a role for PAF in the gentamicininduced nephro-toxicity.     

Modification of biochemical parameters of gentamicin nephrotoxicity by coenzyme Q10 and green tea in rats

The present study was designed to investigate the possible potential protective role of coenzymeQ10 (CoQ10; 10 mg/kg/day, ip) and/or green tea (GT; 25mg/kg/day, po) against gentamicin (GM) nephrotoxicity. Marked increase in the level of serum urea. creatinine and lipid peroxidation (LPO) content was found after administration of gentamicin (80 mg/kg/day, ip) for eight days along with significant decrease in the antioxidant enzymes, superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT) as well as brush border enzymes (Na+/K+ ATPase, Mg(+2)ATPase and Ca2+ ATPase).Treatment with CoQ10 or green tea alone with GM showed significant decrease in serum urea, creatinine and tissue LPO content and significant increase in antioxidant and membrane bound enzymes. Combined treatment with CoQ10 and green tea was more effective in mitigating adverse effect of GM nephrotoxicity. The present work indicated that CoQ10 and green tea due to their antioxidant activity modified the biochemical changes occurred during gentamicin nephrotoxicity and thus had a potential protective effect.     

Evaluation of selected indicators of the renal proximal tubule function in patients treated with gentamicin]

The study aimed at evaluating proximal renal tubule function in patients with nephrolithiasis and chronic pyelonephritis, and in patients with infectious diseases treated with gentamicin. The study involved 2 groups of patients: group A--17 patients with nephrolithiasis and chronic pyelonephritis and group B--30 patients with other infectious diseases (pneumonia, biliary tract infections) but with normal glomerular filtration rate. Patients from both groups were treated with gentamicin in a daily dose of 2-3 mg/kg for 7-10 days. Serum and urine creatinine levels were assayed in all patients prior to, 2-3, 7, 10 days, and after the treatment. Patients assigned to group B were divided into two subgroups: B1 included 15 patients with normal beta 2-microglobulinuria, and B2 15 patients with increased renal loss of beta 2-microglobulin and decreased tubular reabsorption of this protein. Significant increase in beta 2-microglobulinuria was seen on the third day of therapy, the decrease in the tubular reabsorption and glomerular filtration rate were noted in all patients on the seventh day of gentamicin administration. Beta 2-microglobulinuria was significantly higher in patients from groups A and B2 in comparison with group B1 in which no dysfunction of the proximal renal tubule was present before gentamicin therapy. A degree of beta 2-microglobulinuria is an early and sensitive indicator of gentamicin nephrotoxicity. The risk of nephrotixic symptoms is particularly obvious in patients with deteriorated function of renal proximal tubuli before the treatment with gentamicin.