Factors influencing ketorolac-associated perioperative renal dysfunction.

UNLABELLED: Nonsteroidal antiinflammatory drugs (NSAIDs) are useful for the treatment of postoperative pain, but there is continuing concern about adverse effects on renal function. We studied the renal effects of ketorolac in an animal model using Fischer 344 rats undergoing isoflurane anesthesia and laparotomy. Treatment groups--control (C), ketorolac (5 mg x kg(-1) x d(-1)) (K), large-dose ketorolac (15 mg x kg(-1) x d(-1)) (KH), dehydration-ketorolac (5 mg x kg(-1) x d(-1)) (DK), gentamicin (20 mg x kg(-1) x d(-1)) (G), and gentamicin (20 mg x kg(-1) x d(-1)) with ketorolac (5 mg x kg(-1) x d(-1)) (GK)--each comprised 10 animals. Renal function was assessed before laparotomy and after 3 treatment days using concurrent paraaminohippurate and iothalamate clearances, respectively, to estimate renal plasma flow and glomerular filtration rate, and by measuring serum and urine electrolytes, osmolality, urea, and creatinine. A significant increase in serum potassium was found in the GK and DK groups. There were no major changes in renal function in the C, K, KH, and DK groups. Mild renal dysfunction was found in the G group. We found severe and consistent changes in renal function, accompanied by severe, widespread histological changes of acute tubular necrosis, in the GK group. In this postoperative rat model, the combination of ketorolac and gentamicin was deleterious to renal function. IMPLICATIONS: We examined the renal effects of the nonsteroidal antiinflammatory drug ketorolac. Renal function was measured in rats before and after surgery and 3 days' drug administration; the kidneys studied by using microscopy. Only ketorolac plus the antibiotic gentamicin produced marked changes in kidney function and structure.

Urineless estimation of glomerular filtration rate and renal plasma flow in the rat.

A simple method to perform serial renal clearance studies without urine collection in rats is described. This was applied to nonradiolabelled para-aminohippurate sodium (PAH) and iothalamate sodium (IOT) which were used respectively to estimate renal plasma flow (RPF) and glomerular filtration rate (GFR). Under isoflurane-anesthesia the jugular vein and carotid artery of Fischer 344 rats were cannulated, and a loading dose followed by a continuous infusion of PAH and IOT was administered. Steady state was reached after 30 min, and four arterial blood samples were collected over the next 30 min for analysis by HPLC (day 0). The clearances of PAH and IOT were calculated according to Fick's principle as estimates of RPF and GFR from the ratio of the infusion rates to the median solute concentrations. Three days later the femoral artery and vein were cannulated, and the same study was repeated (day 3). There was no significant difference in renal clearances of PAH and IOT between days 0 and 3. The described method gives values that compare well with others in the literature based on other methods and presents an accurate and simple way of detecting changes in renal function before and after a potentially nephrotoxic treatment regimen.