Organic anion infusions exacerbate experimental acute renal failure.
This investigation proposed to determine whether high organic anion (OA) loads per nephron increase renal susceptibility to acute ischemic and nephrotoxic injury. Anesthetized Sprague-Dawley rats were infused with a control infusate, Na2SO4, or an OA (hippurate, p-aminohippurate, cephalothin; 0.125-1.0 mg/min). After a 40-min control period, acute renal injury was induced by either bilateral renal pedicle cross-clamping (X25 min) or by HgCl2 administration (12 mg/kg i.v.). Glomerular filtration rate (clearance of [125I]iothalamate) was determined every 20 min before and after renal injury. Non-OA-infused rats lost 51 +/- 4% (ischemia) and 40 +/- 4% (HgCl2) of control GFR. OA infusion exacerbated this loss of renal function (ischemia, 89 +/- 2%; HgCl2, 84 +/- 4%). Renal histology demonstrated that OA-treated acute renal failure (ARF) rats had more vacuolar degeneration of proximal tubular cells (HgCl2, ischemia) and greater tubular dilatation (ischemia) than did non-OA-treated ARF rats. These functional and histologic responses to OA infusion were not OA dose dependent. Discontinuation of OA infusion did not cause a subsequent rise in GFR. Na2SO4 infusion had no detrimental effects on ischemic ARF. Control rats subjected to prolonged OA infusion (1 mg/min X 5 h) maintained stable GFR and had normal renal histology. ARF rats infused with low-dose cephalothin had terminal serum cephalothin concentrations within a range commonly seen in humans.


CONCLUSIONS
organic anion infusions can exacerbate early functional and histologic parameters of experimental ARF.
D058186:Acute Kidney Injury / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D000618:Aminohippuric Acids / Q000494:pharmacology*; D000818:Animals; D002512:Cephalothin / Q000494:pharmacology*; D003250:Constriction; D005260:Female; D005919:Glomerular Filtration Rate; D006626:Hippurates / Q000494:pharmacology*; D007684:Kidney Tubules / Q000473:pathology; D008627:Mercuric Chloride; D008628:Mercury; D051381:Rats; D011919:Rats, Inbred Strains; D013431:Sulfates / Q000494:pharmacology; D010130:p-Aminohippuric Acid / Q000494:pharmacology*
D000618:Aminohippuric Acids; D006626:Hippurates; D013431:Sulfates; C012036:sodium sulfate; D008627:Mercuric Chloride; D008628:Mercury; D002512:Cephalothin; C030514:hippuric acid; D010130:p-Aminohippuric Acid