Chronic gentamicin nephrotoxicity. Continued tubular injury with preserved glomerular filtration function. 1986

D C Houghton, and D Lee, and D N Gilbert, and W M Bennett

After an initial episode of acute tubular necrosis, apparent resistance to gentamicin nephrotoxicity develops in rats during prolonged drug administration. The authors studied this phenomenon by examining the autoradiographic distribution of 3H-gentamicin and 3H-thymidine during 5 weeks of gentamicin treatment and by analyzing renal structure and function after a 12-week course of treatment. These studies show that regenerating cells exclude gentamicin, but concentrate it again after maturation, and that the rate of thymidine incorporation is still high well after recovery from acute toxic injury. After 12 weeks of gentamicin, the glomerular filtration rate was only modestly diminished, whereas in vitro cortical organic ion transport was substantially impaired. Light and electron microscopy demonstrated all phases of injury and recovery among cells of most proximal tubules and evidence of chronic tubulointerstitial disease. It is concluded that "resistance" to gentamicin is a state of persistent tubular cell injury obscured functionally by preservation of the glomerular filtration rate and histologically by asynchrony of cell necrosis and regeneration.

UI MeSH Term Description Entries
D007687 Kidney Tubules, Proximal The renal tubule portion that extends from the BOWMAN CAPSULE in the KIDNEY CORTEX into the KIDNEY MEDULLA. The proximal tubule consists of a convoluted proximal segment in the cortex, and a distal straight segment descending into the medulla where it forms the U-shaped LOOP OF HENLE. Proximal Kidney Tubule,Proximal Renal Tubule,Kidney Tubule, Proximal,Proximal Kidney Tubules,Proximal Renal Tubules,Renal Tubule, Proximal,Renal Tubules, Proximal,Tubule, Proximal Kidney,Tubule, Proximal Renal,Tubules, Proximal Kidney,Tubules, Proximal Renal
D008854 Microscopy, Electron Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen. Electron Microscopy
D009336 Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply.
D012038 Regeneration The physiological renewal, repair, or replacement of tissue. Endogenous Regeneration,Regeneration, Endogenous,Regenerations
D004351 Drug Resistance Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. Resistance, Drug
D005839 Gentamicins A complex of closely related aminoglycosides obtained from MICROMONOSPORA purpurea and related species. They are broad-spectrum antibiotics, but may cause ear and kidney damage. They act to inhibit PROTEIN BIOSYNTHESIS. Gentamicin Sulfate (USP),Gentamycin,G-Myticin,Garamycin,Gentacycol,Gentamicin,Gentamicin Sulfate,Gentamycins,Gentavet,Genticin,G Myticin,GMyticin,Sulfate, Gentamicin
D005919 Glomerular Filtration Rate The volume of water filtered out of plasma through glomerular capillary walls into Bowman's capsules per unit of time. It is considered to be equivalent to INULIN clearance. Filtration Rate, Glomerular,Filtration Rates, Glomerular,Glomerular Filtration Rates,Rate, Glomerular Filtration,Rates, Glomerular Filtration
D006651 Histocytochemistry Study of intracellular distribution of chemicals, reaction sites, enzymes, etc., by means of staining reactions, radioactive isotope uptake, selective metal distribution in electron microscopy, or other methods. Cytochemistry
D001345 Autoradiography The making of a radiograph of an object or tissue by recording on a photographic plate the radiation emitted by radioactive material within the object. (Dorland, 27th ed) Radioautography
D013936 Thymidine A nucleoside in which THYMINE is linked to DEOXYRIBOSE. 2'-Deoxythymidine,Deoxythymidine,2' Deoxythymidine

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