amphotericin-b and Kidney-Tubular-Necrosis--Acute

In an attempt to modify the cytotoxicity of cisplatin, amphotericin B (AmB) was given as pretreatment to BDIX rats with intracerebral BT4C glioma implants. Ten animals given AmB 5 mg/kg i.p. followed by cisplatin 5 mg/kg i.p. displayed massive haematuria within 24 h after treatment and died a few days later. The antitumoral effect could not, therefore, be evaluated. Histopathological examination of the kidneys showed extensive tubular necrosis. No signs of apoptotic cell death were found using in situ end labelling with biotin-labelled nucleotides or with DNA integrity analysis in agarose gel electrophoresis. An immunohistochemical method for analysis of cisplatin-DNA adducts was used to elucidate the distribution of cisplatin in brain tumour, normal brain and kidney. Addition of AmB to cisplatin caused increased adduct formation in kidneys, particularly in tubular cells. It seems plausible that the nephrotoxicity, at least in part, was mediated by increased levels of cisplatin-DNA adducts. Pretreatment with AmB did not have any obvious effect on the formation of adducts in the cerebral cortex. The adduct levels in the tumours from animals pretreated with AmB were not significantly increased compared with those treated with cisplatin only. Thus, addition of AmB to cisplatin caused excessive nephrotoxicity suggesting a decrease in the therapeutic ratio of cisplatin.

Topics: Amphotericin B; Animals; Antineoplastic Agents; Apoptosis; Cisplatin; DNA Adducts; DNA, Neoplasm; Drug Interactions; Glioma; Kidney Tubular Necrosis, Acute; Neoplasm Transplantation; Rats; Rats, Inbred Strains

Topics: Aminoglycosides; Amphotericin B; Anti-Bacterial Agents; Cisplatin; Contrast Media; Hemolytic-Uremic Syndrome; Humans; Kidney Tubular Necrosis, Acute; Mannitol; Methotrexate; Nephritis, Interstitial; Paraquat

Topics: Amphotericin B; Bone Neoplasms; Child, Preschool; Diphosphonates; Histoplasmosis; Humans; Kidney; Kidney Tubular Necrosis, Acute; Male; Radionuclide Imaging; Technetium; Technetium Tc 99m Medronate

An adult renal transplant recipient was complicated with cryptococcal lung granuloma and meningitis. Treatment with the antifungal agents, 5-fluorocytocin and clotrimazole had to be discontinued due to side effects. Whereas, the intrathecal administration of amphotericin B proved effective for meningitis but intravenously it induced acute tubular necrosis to the transplanted kidney. In order to cure the persistant fungal lung granulomas in renal transplant patients early surgical excision seems to be essential.

Topics: Acute Kidney Injury; Adult; Amphotericin B; Cryptococcosis; Granuloma; Humans; Immunosuppressive Agents; Kidney Transplantation; Kidney Tubular Necrosis, Acute; Lung Diseases, Fungal; Male; Meningitis; Postoperative Complications; Transplantation, Homologous