Iron Depletion in the Remnant Kidney

Abstract

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.

Effect of iron restriction on renal damage and mineralocorticoid receptor signaling in a rat model of chronic kidney disease

“…This salutary effect of iron restriction on renal damage is consistent with the results previously reported in the different models of renal disease [20,21]. However, our observation differs from a previous report of remnant kidney model rats, in which iron restriction did not have protective effects on renal damage [22]. There are two plausible explanations for what appear to be conflicting data.…”

“…On the other hand, it is conceivable that the differences may be caused by differences in the experimental protocol. Nankivell and Harris [22] provided iron restriction and periodic phlebotomy before surgery or throughout the experiment, whereas we supplied just only iron restriction from 1 week after surgery in CKD rats. In this study, we found a beneficial effect of dietary iron restriction on renal damage and hypertension in a rat model of CKD through the inhibition of renal mineralocorticoid receptor signaling.…”

Iron metabolism in the pathogenesis of iron-induced kidney injury

“…36,62 In addition, kidney and urinary iron content is increased in patients 3,17,[63][64][65][66][67][68][69][70][71] and animal models of AKI and CKD. 3,6,14,[71][72][73][74][75][76][77][78][79][80] Finally, the severity of kidney injury can be reduced by iron-deficient diets, the use of iron chelators or treatment directed at reducing iron-related oxidative stress in animal models. 3,15,19,71,79,[81][82][83] Direct evidence of renal toxic effects of iron is, however, limited in humans.…”

Comprehensive Analysis of the Spatial Distribution of Gadolinium, Iron, Manganese, and Phosphorus in the Brain of Healthy Rats After High-Dose Administrations of Gadodiamide and Gadobutrol

“…One study analyzed selected homogenized brain portions and found correlations between Gd and Fe concentrations after administration of linear GBCAs 42 . However, the rats in this study were subtotally nephrectomized, which impairs renal elimination of the GBCA, and moreover causes severe urinary Fe loss 60 …”

“…42 However, the rats in this study were subtotally nephrectomized, which impairs renal elimination of the GBCA, and moreover causes severe urinary Fe loss. 60 From visual inspection of Gd-Fe overlay images after gadodiamide, a rather weak colocalization could be surmised in the OB, in the DCN, and in the IC. On the other hand, distinctive distribution patterns of both Fe and Gd were determined, respectively, but found not to be congruent, for example, in the Hi and the GrCb.…”