title: Organic anion infusions exacerbate experimental acute renal failure.
abstract: 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.
mesh_terms: 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*
chemical_list: D000618:Aminohippuric Acids; D006626:Hippurates; D013431:Sulfates; C012036:sodium sulfate; D008627:Mercuric Chloride; D008628:Mercury; D002512:Cephalothin; C030514:hippuric acid; D010130:p-Aminohippuric Acid