Pathophysiology of a nephrotoxic model of acute renal failure.
Studies were performed in the dog to determine the mechanism of the renal functional impairment which follows the administration of the nephrotoxic agent, uranyl nitrate. In the first series of 28 experiments, total renal blood flow was determined with the radioactive microsphere method before and after uranyl nitrate administration, 10 mg/kg. Total blood flow fell from 199 to 121 ml/min 6 hr after administration of uranyl nitrate (P less than 0.001) but was unchanged 48 hr after administration of the drug. Yet the blood urea nitrogen concentration had increased from a control value of 13 to 120 mg/100 ml at 48 hr (P less than 0.001). Since renal blood flow was normal at 48 hr, micropuncture studies were performed to further evaluate the mechanism of the renal impairment. In the first group of nine studies using a 10 mg/kg dose of uranyl nitrate, nephron glomerular filtration rate (GFR) was reduced 37% while total kidney GFR averaged less than 1% of normal. A similar disparity between superficial and total GFR was noted after a 5 mg/kg dose even though urine flow was comparable to values found in normal hydropenic dogs. Proximal tubular transit time and intratubular pressure were normal. The recovery of 3H-inulin injected into the proximal tubule was 97% in normal dogs and 14% in uranyl nitrate dogs (P less than 0.001). Since there was no difference between early and late proximal tubular nephron GFR, it was suggested that the pars recta, the segment most severely involved histologically, was the main site of inulin leak. Scanning electron microscopy revealed an alteration in epithelial architecture which may have accounted, at least in part, for the diminution in nephron GFR. These studies are interpreted to indicate that the impairment in renal function in this model is due to both leakage of filtrate across damaged tubular epithelium and a modest decrease in nephron GFR.
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000503:physiopathology* / Q000652:urine; D000818:Animals; D001794:Blood Pressure; D004195:Disease Models, Animal; D004285:Dogs; D004848:Epithelium / Q000648:ultrastructure; D005919:Glomerular Filtration Rate; D007444:Inulin / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D007672:Kidney Cortex / Q000503:physiopathology; D007687:Kidney Tubules, Proximal / Q000378:metabolism; D008863:Microspheres; D009399:Nephrons / Q000503:physiopathology; D010477:Perfusion; D010539:Permeability; D012039:Regional Blood Flow / Q000187:drug effects; D013997:Time Factors; D014502:Uranyl Nitrate
D014502:Uranyl Nitrate; D007444:Inulin