Iron depletion in the remnant kidney.
Urinary and proximal tubular iron are increased after subtotal nephrectomy, and iron depletion has been shown to be beneficial in proteinuric models of chronic renal disease in rats. In this study, iron depletion by low iron pair-fed diet and periodic phlebotomy was induced for 6 months in rats with partial (5/6) nephrectomy, resulting in a reduction in hematocrit and serum iron in all iron-deficiency subgroups. Tubular iron, assessed by energy dispersive analysis and electron microscopy, was reduced in quantity but not number of iron-containing lysosomes only within 1 subgroup of severe iron deficiency (p < 0.05). There was no improvement in serial isotopic glomerular filtration rate measurements, urinary protein and transferrin excretion, tubular damage scores, serum creatinine, or measures of reactive oxygen species (ROS) generation. In a subgroup of rats with no supplementation of sulfhydryl amino acids (cysteine and methionine) which can act as ROS scavengers, iron deficiency increased urinary protein excretion (213.3 +/- 23.0 mg/24 h, mean +/- SEM, vs. 87.4 +/- 16.1, p < 0.001), urinary transferrin excretion (p < 0.05), kidney weight (p < 0.05) and tissue malondialdehyde, a lipid peroxidation product (0.78 +/- 0.16 nmol/mg protein vs. 0.57 +/- 0.19, p < 0.05), consistent with increased ROS generation. Hence, no beneficial effect of iron-deficiency was demonstrated by any measure of structure of function in the remnant kidney, and it may enhance damage if sulfhydryl repletion is not provided.
D000596:Amino Acids / Q000008:administration & dosage; D000818:Animals; D007501:Iron / Q000008:administration & dosage* / Q000378:metabolism*; D000090463:Iron Deficiencies; D007668:Kidney / Q000378:metabolism*; D007674:Kidney Diseases / Q000517:prevention & control; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009392:Nephrectomy; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000008:administration & dosage
D000596:Amino Acids; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; D008315:Malondialdehyde; D007501:Iron