title: Precipitable tissue proteins can cause experimental acute renal failure.
abstract: A previous investigation demonstrated that intravenous infusion of a saline-liver extract into rats causes acute renal failure (ARF), manifested by severe azotemia, extensive cast formation, and patchy tubular necrosis. The purpose of the present study was to explore its pathogenesis. Histologic assessments of rat kidneys made 1.5 hours after liver extract infusion demonstrated eosinophilic material within glomerular capillaries, Bowman's space, and proximal tubular lumina, distal nephron cast formation, and tubular dilation without evidence of tubular necrosis. Renal blood flow at this time was normal but the rats were anuric. Assessments made 24 hours after liver extract infusion demonstrated persisting ARF (blood urea nitrogen, 132 +/- 8; creatinine, 2.54 +/- 0.19 mg/dl), profound cast deposition almost exclusively in the inner medulla/papilla, and the appearance of patchy proximal tubular necrosis. Sephacryl S200 fractionation and 10% polyacrylamide gel electrophoresis of liver extract showed high and low molecular weight proteins (less than 30,000). Proteins in both regions demonstrated prominent acid precipitability (pH 4.5) and autoaggregation (at 37 degrees C). Trace amounts of spontaneously precipitated protein recovered from urine during liver extract infusion demonstrated a predominance of low molecular weight proteins by polyacrylamide gel electrophoresis. Infusing rats with filterable low molecular weight proteins (cytochrome c, ribonuclease, myoglobin) without autoaggregation/acid precipitation characteristics or liver extract made devoid of precipitable proteins failed to induce ARF. However, infusing a kidney extract containing acid precipitating/autoaggregating proteins caused inner medullary/papillary cast formation and ARF.
  
  
  CONCLUSIONS
  normal parenchymal tissues contain proteins which can undergo glomerular filtration and which can spontaneously aggregate under conditions which exist in the distal nephron. If released into the circulation, or if shed from tubular cells into lumina after nephrotoxic or ischemic renal injury, they could help to induce intratubular obstruction and ARF.
authors.affiliation: Department of Medicine, University of Washington, Seattle.
authors.forename: R A
authors.initials: RA
authors.lastname: Zager
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology*; D000818:Animals; D011232:Chemical Precipitation; D002850:Chromatography, Gel; D004231:Diuresis; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D008110:Liver Extracts / Q000032:analysis / Q000633:toxicity*; D011506:Proteins / Q000032:analysis / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D008110:Liver Extracts; D011506:Proteins