The renal concentrating defect after gentamicin administration in the rat.
The present studies were carried out to delineate the mechanism of the polyuric state and renal concentration defect seen after gentamicin. Gentamicin was given at a dosage of 100 mg/kg/day subcutaneously for either 4 or 5 days to Sprague-Dawley rats and resulted in a reversible, polyuric form of acute renal failure. This nonoliguric acute renal failure was accompanied by significant polydipsia and a renal concentrating defect 11 days after gentamicin. To assess the role of polydipsia in the polyuria and renal concentrating abnormality, water intake was restricted in gentamicin-treated animals to match intake of control animals. Elimination of the polydipsia failed to eliminate the polyuria and to improve the renal concentrating abnormality. Postdehydration plasma vasopressin levels were higher in gentamicin-treated than control animals, suggesting that the renal concentrating defect was nephrogenic in origin. Daily urinary prostaglandin E2 excretion was comparable in gentamicin-treated and control animals. However, indomethacin failed to improve urinary concentrating ability, suggesting that the renal concentrating defect was prostaglandin E2 independent. Finally, depressed postdehydration inner medullary tonicity was found in gentamicin-treated animals In summary, gentamicin administration in the rat was associated with a reversible polyuric form of acute renal failure and a renal concentrating defect. This concentration defect was nephrogenic in origin, independent of polydipsia and prostaglandin E2, and was associated with a decrease in inner medullary tonicity.
D058186:Acute Kidney Injury / Q000139:chemically induced; D000818:Animals; D015232:Dinoprostone; D005839:Gentamicins / Q000009:adverse effects / Q000494:pharmacology*; D007671:Kidney Concentrating Ability / Q000187:drug effects*; D007679:Kidney Medulla / Q000187:drug effects; D008297:Male; D011141:Polyuria / Q000139:chemically induced; D011458:Prostaglandins E / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D014667:Vasopressins / Q000097:blood; D014868:Water Deprivation
D005839:Gentamicins; D011458:Prostaglandins E; D014667:Vasopressins; D015232:Dinoprostone