Oxygen consumption and oxidant stress in surviving nephrons.
We investigated the effects of reduction of renal mass on rates of oxygen consumption, sodium transport, and indexes of oxidant stress in surviving nephrons. Rates of oxygen consumption in surviving nephrons were elevated by more than twofold compared with nephrons in intact kidneys in rats on standard protein intakes. Absolute rates of sodium reabsorption (TNa) in the surviving nephrons were increased with a lower ratio of TNa to oxygen consumption. To determine oxidant stress, we measured malondialdehyde (MDA) in the kidney and urine and the glutathione redox ratio in kidney tissue. MDA per nephron was increased in the subtotally nephrectomized model and was accompanied by increased absolute and fractional urinary excretion of MDA but not by an increase in kidney MDA per milligram protein. The glutathione redox ratios were similar. Since increased dietary protein intake worsens renal injury, we studied the effects of dietary protein manipulation (30 vs. 6%) on oxygen consumption, MDA levels, and the glutathione redox ratio. The kidneys of subtotally nephrectomized animals maintained on 30% protein diets exhibited increased rates of oxygen consumption. Increased dietary protein intake led to increased MDA per nephron, increased urinary excretion of MDA, and increased MDA per milligram protein in subtotally nephrectomized animals, and markedly increased the glutathione redox ratio. We conclude that, despite increased oxygen consumption, surviving nephrons compared with intact nephrons in rats on standard protein intake demonstrate no evidence of oxidant stress. Increased urinary clearance of MDA may provide a mechanism that prevents the buildup of lipid peroxidation. Subjecting the remnant nephron to increased protein increases oxygen consumption and imposes oxidant stress.(ABSTRACT TRUNCATED AT 250 WORDS)
Nath
K A
KA
Department of Medicine, University of Minnesota, Minneapolis 55455.
Croatt
A J
AJ
Hostetter
T H
TH
D000818:Animals; D004044:Dietary Proteins / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism*; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism / Q000652:urine; D009392:Nephrectomy / Q000379:methods; D009399:Nephrons / Q000378:metabolism*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013312:Stress, Physiological / Q000378:metabolism*
D004044:Dietary Proteins; D008054:Lipid Peroxides; D008315:Malondialdehyde; D005978:Glutathione