Dietary protein alters tubular iron accumulation after partial nephrectomy.
Reactive oxygen species (ROS) have been implicated in progression of disease in the rat remnant kidney (RK) model of chronic renal failure. Substantial amounts of iron accumulate in proximal tubular lysosomes of RK and could damage tubules by ROS generation. The effect of dietary protein intake on ROS, tubular damage and iron accumulation assessed by energy dispersive analysis was determined in RK (5/6 nephrectomy, N = 12) and sham-operated kidneys (SO, N = 10). In RK, mean lysosomal iron concentration, urinary iron and protein excretion and morphological damage were increased and GFR decreased. Dietary protein loading (40% vs. 12%) increased the number of iron-containing lysosomes (P < 0.05) and the mean lysosomal iron (P < 0.02) in proximal tubular cells after four weeks. In RK, high protein diet increased renal weight (P < 0.01), numerical density of iron-containing lysosomes and tubular damage (both P < 0.05). ROS generation, assessed by tissue and plasma malondialdehyde (MDA), was also increased (both P < 0.05). Plasma MDA correlated with tubular iron accumulation (r = 0.75). In RK fed a high protein diet (N = 18) treatment with the iron-chelator desferrioxamine reduced serum iron, urinary volume, and tubular iron accumulation and damage compared to controls (P < 0.01). In summary, in RK dietary protein manipulation altered urinary iron and protein excretion, proximal tubular iron accumulation, renal cortical ROS generation and ultrastructural damage. Desferrioxamine treatment reduced tubular lysosomal iron and ultrastructural damage. These results suggest a role for tubular iron as a determinant of tubular injury associated with dietary protein loading in rats with partial nephrectomy.
Nankivell
B J
BJ
Department of Renal Medicine, Westmead Hospital, Sydney, NSW, Australia.
Tay
Y C
YC
Boadle
R A
RA
Harris
D C
DC
D000818:Animals; D003676:Deferoxamine / Q000494:pharmacology; D004044:Dietary Proteins / Q000494:pharmacology*; D005919:Glomerular Filtration Rate; D005978:Glutathione / Q000032:analysis; D007501:Iron / Q000378:metabolism*; D007668:Kidney / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D007684:Kidney Tubules / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D009392:Nephrectomy; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000032:analysis; D014168:Transferrin / Q000378:metabolism
D004044:Dietary Proteins; D017382:Reactive Oxygen Species; D014168:Transferrin; D008315:Malondialdehyde; D007501:Iron; D005978:Glutathione; D003676:Deferoxamine