Document Detail


Chronic tubulointerstitial nephritis and renal insufficiency associated with long-term "subtherapeutic" gentamicin.
MedLine Citation:
PMID:  3193025     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
D C Houghton; J English; W M Bennett
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
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:
Created Date:  1989-01-12     Completed Date:  1989-01-12     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0375375     Medline TA:  J Lab Clin Med     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  694-703     Citation Subset:  AIM; IM    
Affiliation:
Department of Pathology, Oregon Health Sciences University, Portland 97201.
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MeSH Terms
Descriptor/Qualifier:
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:
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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