Toxicity of tubule fluid iron in the nephrotic syndrome.
This study was carried out in rats with nephrotoxic serum nephritis after autologous phase proteinuria was well established to determine the effect of tubule fluid iron chelation on the course of this disease. Deferoxamine administration caused a reduction in urinary iron potentially capable of catalyzing hydroxyl radical (.OH) formation and kidney iron uptake (224 +/- 60 vs. 398 +/- 152 mg/kg). This was associated with a decrease rate of progression of renal failure over the 21-day study period (creatinine clearance -0. 199 +/- 0.152 vs. -0.509 +/- 0.336 ml/min, P < 0.05) and improved survival (8/8 vs. 4/8, P < 0.05). In addition deferoxamine caused a reduction in urinary transferrin excretion (32 +/- 15 vs. 74 +/- 16 mg/day) and fractional excretion of transferrin (2.01 +/- 1 vs. 5.9 +/- 3.7%) and an increase in serum transferrin levels (229 +/- 36 vs. 139 +/- 45 mg/dl, all P < 0.05). It is suggested that iron presented to the tubule fluid as a result of the glomerular leak for transferrin is dissociated from transferrin. In turn the iron is available in a form capable of catalyzing .OH formation, resulting in lipid peroxidation of tubule cell membranes. Deferoxamine chelation of tubule fluid iron retards the development of both tubulointerstitial injury and superimposed glomerular sclerosis in this model of membranous nephropathy.
Alfrey
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AC
Denver Veterans Affairs Hospital, University of Colorado Medical Center 80220.
D000818:Animals; D001761:Bleomycin; D003404:Creatinine / Q000378:metabolism; D003676:Deferoxamine / Q000494:pharmacology; D007501:Iron / Q000009:adverse effects* / Q000378:metabolism / Q000652:urine; D007502:Iron Chelating Agents / Q000494:pharmacology; D007684:Kidney Tubules / Q000378:metabolism*; D008297:Male; D009404:Nephrotic Syndrome / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014168:Transferrin / Q000652:urine
D007502:Iron Chelating Agents; D014168:Transferrin; D001761:Bleomycin; D003404:Creatinine; D007501:Iron; D003676:Deferoxamine