| Chronic tubulointerstitial nephritis and renal insufficiency associated with long-term "subtherapeutic" gentamicin. | |
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MedLine Citation:
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PMID: 3193025 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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To determine whether long-term "subtherapeutic" concentrations of aminoglycoside produce chronic tubulointerstitial nephropathy, Fisher rats were given gentamicin, 20 mg/kg/day, for up to 6 months via indwelling osmotic infusion pumps. Studies included renal histology, autoradiographic quantitation of renal cell tritiated thymidine uptake, renal function and renal cortical gentamicin assay. Acute proximal tubular injury, without tubular necrosis, followed by recovery, occurred during the first month. Subsequently only mild, nonprogressive tubulointerstitial changes and a twofold increase in tubular cell turnover were observed. Inulin clearance fell more than 50% during the 6 months of treatment compared with 10% in age-matched controls. Serum creatinine and creatinine clearance overestimated glomerular filtration rate during treatment and did not distinguish treated animals from controls. During the month after 6 months of gentamicin, tubular microcystic changes and active tubulointerstitial nephritis developed, with a continued fall in inulin clearance. In summary, gentamicin, in "subtherapeutic" doses, produces mild chronic tubulointerstitial nephritis with progressive renal failure. Cessation of treatment is associated with microcystic and inflammatory changes, suggesting that the renal response to tubular injury can be dissociated from the amount of toxin in the renal cortex. Keeping serum aminoglycoside levels below accepted therapeutic range for 6 months did not preclude nephrotoxicity. |
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Authors:
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D C Houghton; J English; W M Bennett |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Journal of laboratory and clinical medicine Volume: 112 ISSN: 0022-2143 ISO Abbreviation: J. Lab. Clin. Med. Publication Date: 1988 Dec |
Date Detail:
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Created Date: 1989-01-12 Completed Date: 1989-01-12 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0375375 Medline TA: J Lab Clin Med Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 694-703 Citation Subset: AIM; IM |
Affiliation:
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Department of Pathology, Oregon Health Sciences University, Portland 97201. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Autoradiography Gentamicins / administration & dosage, metabolism, toxicity* Glomerular Filtration Rate / drug effects Inulin / diagnostic use Kidney Failure, Chronic / chemically induced*, metabolism, pathology Male Nephritis, Interstitial / chemically induced*, metabolism, pathology Rats Rats, Inbred F344 Thymidine / diagnostic use |
| Chemical | |
Reg. No./Substance:
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0/Gentamicins; 50-89-5/Thymidine; 9005-80-5/Inulin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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