fosfomycin and Kidney-Tubular-Necrosis--Acute

Cisplatin induces nephrotoxicity and this study evaluated the protective effect of fosfomycin on it in 11 gynecological cancer patients.. The N-acetyl-beta-D-glucosaminidase (NAG), beta 2-microglobulin (beta 2MG), creatinine (uCr) and total protein (TP) levels in a 24-hour urine specimen as well as the blood urea nitrogen (BUN) and serum creatinine (sCr) were measured before and after CAPF chemotherapy alone (control) or with fosfomycin.. The results were statistically analyzed by using the t-test. NAG, beta 2MG, uCr and TP levels increased significantly after chemotherapy in the control patients, but BUN and sCr levels did not change significantly. The NAG level in the control group was twice as high as in the fosfomycin group 8 days after chemotherapy (p < 0.01). The uCr and TP in control patients increased significantly after chemotherapy when compared to those in patients coad-ministered fosfomycin. There were no significant changes in beta 2MG, BUN and sCr levels.. Cisplatin affected the levels of NAG, beta 2MG, uCr and TP without influencing BUN and sCr levels. Fosfomycin, therefore, may be useful as a supplemental treatment for reducing cisplatin nephrotoxicity, especially proximal tubular damage.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cross-Over Studies; Female; Fosfomycin; Genital Neoplasms, Female; Gentamicins; Humans; Kidney; Kidney Tubular Necrosis, Acute

The effect of coadministration of fosfomycin (FOM) on nedaplatin-induced nephrotoxicity in rats was investigated for 6 days. FOM decreased nedaplatin-induced nephrotoxicity, as shown by reduced blood urea nitrogen (BUN), serum creatinine levels, and urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG). Further, there were fewer histopathological signs of nephrotoxicity in the groups treated with the combination of nedaplatin and FOM as compared with the nedaplatin-alone group. The concentration of nedaplatin was significantly lower in the renal cortex of rats treated with the combination of nedaplatin and FOM as compared with those treated with nedaplatin alone (p < 0.05). In conclusion, the concomitant administration of FOM and nedaplatin may help to achieve a chemotherapeutic strategy that reduces the nephrotoxic effects of nedaplatin.

Topics: Acetylglucosaminidase; Animals; Blood Urea Nitrogen; Creatinine; Disease Models, Animal; Fosfomycin; Injections, Intraperitoneal; Kidney Tubular Necrosis, Acute; Male; Organoplatinum Compounds; Random Allocation; Rats; Rats, Wistar

We studied in an experimental rat model, if fosfomycin reduces the tubulotoxicity induced by tobramycin, teicoplanin, cisplatin or ciclosporine A and is thus a nephroprotective agent. 10 female wistar rats per dose and compound were used, measures of tubulotoxicity were urinary excretion rates of tubular cells and malate dehydrogenase on 5 successive days. Fosfomycin proved to be a potent nephroprotector against all 4 nephrotoxins. Its activity was not based on pharmacokinetic interactions but on a pharmacodynamic effect. Presumably, fosfomycin stabilises the membranes of lysosomes in tubular cells.

Topics: Acute Kidney Injury; Animals; Cisplatin; Cyclosporins; Dose-Response Relationship, Drug; Female; Fosfomycin; Glycopeptides; Kidney Tubular Necrosis, Acute; Kidney Tubules; Rats; Rats, Inbred Strains; Teicoplanin; Tobramycin

The continued chemotherapeutic application of cisplatin (cis-diamminedichloroplatinum [II]) necessitates reduction of its dose-limiting toxicity without decreasing its tumoricidal effect. This research project evaluated the efficacy of fosfomycin, a phosphonic acid antibiotic, in decreasing or ameliorating the ototoxicity (high frequency sensorineural hearing loss) and nephrotoxicity (renal tubular necrosis and interstitial nephritis) of cisplatin. Experimentally, fosfomycin effectively inhibits aminoglycoside-induced ototoxicity and nephrotoxicity in animals and humans. The efficacy of fosfomycin in blocking platinum-induced toxicity in the guinea pig was evaluated histologically and functionally using cytocochleography and light microscopy of the organ of Corti and the auditory brain stem evoked response (ABR), and light microscopy of renal corticomedullary tissues, small bowel, liver, lung, and peripheral nerve. The results demonstrate that fosfomycin ameliorates the acute renal tubular necrosis and interstitial nephritis and markedly inhibits the elevation of ABR thresholds and simultaneous outer hair cell loss that can result from cisplatinum administration. Fosfomycin should be considered a potential antidote for the dose-limiting ototoxicity and nephrotoxicity of cisplatin chemotherapy.

Topics: Acute Kidney Injury; Animals; Cisplatin; Evoked Potentials, Auditory; Fosfomycin; Guinea Pigs; Hearing Loss, Sensorineural; Kidney; Kidney Tubular Necrosis, Acute; Nephritis, Interstitial