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Erschienen in: Pediatric Nephrology 8/2008

01.08.2008 | Editorial Commentary

Iron, oxidative stress, and clinical outcomes

verfasst von: Rajiv Agarwal

Erschienen in: Pediatric Nephrology | Ausgabe 8/2008

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Abstract

It is well known that iron is pro-oxidant. Chronic kidney disease (CKD) is a pro-oxidant state, and intravenous administration of iron is frequently used to correct anemia. On one hand, there is little doubt that iron causes oxidative stress. On the other, it is far from clear whether oxidative stress, so generated, leads to poor clinical outcomes. Iron has benefits that may be independent of the correction of anemia. Furthermore, concerns surround the use of high doses of erythropoietin in causing excess heart failure and death in patients with CKD. Thus, it would be prudent if iron were to continue to be used judiciously in patients who require erythropoietin. Iron, given orally, would be the preferred first-line agent in patients not on hemodialysis. In patients with sepsis, intravenous treatment with iron should be avoided, because, in animal experiments, intravenous administration of iron can compound the inflammatory response and increase mortality. Clinical trials are needed to ascertain the risk and benefits of the intravenous administration of iron in patients with CKD.
Literatur
1.
2.
Zurück zum Zitat Zager RA, Johnson AC, Hanson SY, Wasse H (2002) Parenteral iron formulations: a comparative toxicologic analysis and mechanisms of cell injury. Am J Kidney Dis 40:90–103PubMed Zager RA, Johnson AC, Hanson SY, Wasse H (2002) Parenteral iron formulations: a comparative toxicologic analysis and mechanisms of cell injury. Am J Kidney Dis 40:90–103PubMed
3.
Zurück zum Zitat Zager RA, Johnson AC, Hanson SY (2004) Parenteral iron nephrotoxicity: Potential mechanisms and consequences. Kidney Int 66:144–156PubMed Zager RA, Johnson AC, Hanson SY (2004) Parenteral iron nephrotoxicity: Potential mechanisms and consequences. Kidney Int 66:144–156PubMed
4.
Zurück zum Zitat Zager RA, Johnson AC, Hanson SY (2004) Proximal tubular cytochrome c efflux: determinant, and potential marker, of mitochondrial injury. Kidney Int 65:2123–2134PubMed Zager RA, Johnson AC, Hanson SY (2004) Proximal tubular cytochrome c efflux: determinant, and potential marker, of mitochondrial injury. Kidney Int 65:2123–2134PubMed
5.
Zurück zum Zitat Agarwal R, Campbell RC, Warnock DG (2004) Oxidative stress in hypertension and chronic kidney disease: role of angiotensin II. Semin Nephrol 24:101–114PubMed Agarwal R, Campbell RC, Warnock DG (2004) Oxidative stress in hypertension and chronic kidney disease: role of angiotensin II. Semin Nephrol 24:101–114PubMed
6.
Zurück zum Zitat Rooyakkers TM, Stroes ES, Kooistra MP, van Faassen EE, Hider RC, Rabelink TJ, Marx JJ (2002) Ferric saccharate induces oxygen radical stress and endothelial dysfunction in vivo. Eur J Clin Invest 32[Suppl 1]:9–16PubMed Rooyakkers TM, Stroes ES, Kooistra MP, van Faassen EE, Hider RC, Rabelink TJ, Marx JJ (2002) Ferric saccharate induces oxygen radical stress and endothelial dysfunction in vivo. Eur J Clin Invest 32[Suppl 1]:9–16PubMed
7.
Zurück zum Zitat Agarwal R, Vasavada N, Sachs NG, Chase S (2004) Oxidative stress and renal injury with intravenous iron in patients with chronic kidney disease. Kidney Int 65:2279–2289PubMed Agarwal R, Vasavada N, Sachs NG, Chase S (2004) Oxidative stress and renal injury with intravenous iron in patients with chronic kidney disease. Kidney Int 65:2279–2289PubMed
8.
Zurück zum Zitat Agarwal R (2005) On the nature of proteinuria with acute renal injury in patients with chronic kidney disease. Am J Physiol Renal Physiol 288:F265–F271PubMed Agarwal R (2005) On the nature of proteinuria with acute renal injury in patients with chronic kidney disease. Am J Physiol Renal Physiol 288:F265–F271PubMed
9.
Zurück zum Zitat Agarwal R (2006) Proinflammatory effects of iron sucrose in chronic kidney disease. Kidney Int 69:1259–1263PubMed Agarwal R (2006) Proinflammatory effects of iron sucrose in chronic kidney disease. Kidney Int 69:1259–1263PubMed
10.
Zurück zum Zitat Leehey DJ, Palubiak DJ, Chebrolu S, Agarwal R (2005) Sodium ferric gluconate causes oxidative stress but not acute renal injury in patients with chronic kidney disease: a pilot study. Nephrol Dial Transplant 20:135–140PubMed Leehey DJ, Palubiak DJ, Chebrolu S, Agarwal R (2005) Sodium ferric gluconate causes oxidative stress but not acute renal injury in patients with chronic kidney disease: a pilot study. Nephrol Dial Transplant 20:135–140PubMed
11.
Zurück zum Zitat Agarwal R, Rizkala AR, Kaskas MO, Minasian R, Trout JR (2007) Iron sucrose causes greater proteinuria than ferric gluconate in non-dialysis chronic kidney disease. Kidney Int 72:638–642PubMed Agarwal R, Rizkala AR, Kaskas MO, Minasian R, Trout JR (2007) Iron sucrose causes greater proteinuria than ferric gluconate in non-dialysis chronic kidney disease. Kidney Int 72:638–642PubMed
12.
Zurück zum Zitat Lim PS, Wei YH, Yu YL, Kho B (1999) Enhanced oxidative stress in haemodialysis patients receiving intravenous iron therapy. Nephrol Dial Transplant 14:2680–2687PubMed Lim PS, Wei YH, Yu YL, Kho B (1999) Enhanced oxidative stress in haemodialysis patients receiving intravenous iron therapy. Nephrol Dial Transplant 14:2680–2687PubMed
13.
Zurück zum Zitat Roob JM, Khoschsorur G, Tiran A, Horina JH, Holzer H, Winklhofer-Roob BM (2000) Vitamin E attenuates oxidative stress induced by intravenous iron in patients on hemodialysis. J Am Soc Nephrol 11:539–549PubMed Roob JM, Khoschsorur G, Tiran A, Horina JH, Holzer H, Winklhofer-Roob BM (2000) Vitamin E attenuates oxidative stress induced by intravenous iron in patients on hemodialysis. J Am Soc Nephrol 11:539–549PubMed
14.
Zurück zum Zitat Salahudeen AK, Oliver B, Bower JD, Roberts LS 2nd (2001) Increase in plasma esterified F2-isoprostanes following intravenous iron infusion in patients on hemodialysis. Kidney Int 60:1525–1531PubMed Salahudeen AK, Oliver B, Bower JD, Roberts LS 2nd (2001) Increase in plasma esterified F2-isoprostanes following intravenous iron infusion in patients on hemodialysis. Kidney Int 60:1525–1531PubMed
15.
Zurück zum Zitat Drueke T, Witko-Sarsat V, Massy Z, Descamps-Latscha B, Guerin AP, Marchais SJ, Gausson V, London GM (2002) Iron therapy, advanced oxidation protein products, and carotid artery intima-media thickness in end-stage renal disease. Circulation 106:2212–2217PubMed Drueke T, Witko-Sarsat V, Massy Z, Descamps-Latscha B, Guerin AP, Marchais SJ, Gausson V, London GM (2002) Iron therapy, advanced oxidation protein products, and carotid artery intima-media thickness in end-stage renal disease. Circulation 106:2212–2217PubMed
16.
Zurück zum Zitat Anraku M, Kitamura K, Shinohara A, Adachi M, Suenga A, Maruyama T, Miyanaka K, Miyoshi T, Shiraishi N, Nonoguchi H, Otagiri M, Tomita K (2004) Intravenous iron administration induces oxidation of serum albumin in hemodialysis patients. Kidney Int 66:841–848PubMed Anraku M, Kitamura K, Shinohara A, Adachi M, Suenga A, Maruyama T, Miyanaka K, Miyoshi T, Shiraishi N, Nonoguchi H, Otagiri M, Tomita K (2004) Intravenous iron administration induces oxidation of serum albumin in hemodialysis patients. Kidney Int 66:841–848PubMed
17.
Zurück zum Zitat Attallah N, Osman-Malik Y, Frinak S, Besarab A (2006) Effect of intravenous ascorbic acid in hemodialysis patients with EPO-hyporesponsive anemia and hyperferritinemia. Am J Kidney Dis 47:644–654PubMed Attallah N, Osman-Malik Y, Frinak S, Besarab A (2006) Effect of intravenous ascorbic acid in hemodialysis patients with EPO-hyporesponsive anemia and hyperferritinemia. Am J Kidney Dis 47:644–654PubMed
18.
Zurück zum Zitat Eiselt J, Racek J, Opatrny K Jr, Trefil L, Stehlík P (2006) The effect of intravenous iron on oxidative stress in hemodialysis patients at various levels of vitamin C. Blood Purif 24:531–537PubMed Eiselt J, Racek J, Opatrny K Jr, Trefil L, Stehlík P (2006) The effect of intravenous iron on oxidative stress in hemodialysis patients at various levels of vitamin C. Blood Purif 24:531–537PubMed
19.
Zurück zum Zitat Johnson RJ, Herrera-Acosta J, Schreiner GF, Rodriguez-Iturbe B (2002) Subtle acquired renal injury as a mechanism of salt-sensitive hypertension. N Engl J Med 346:913–923PubMed Johnson RJ, Herrera-Acosta J, Schreiner GF, Rodriguez-Iturbe B (2002) Subtle acquired renal injury as a mechanism of salt-sensitive hypertension. N Engl J Med 346:913–923PubMed
20.
Zurück zum Zitat Haugen E, Nath KA (1999) The involvement of oxidative stress in the progression of renal injury. Blood Purif 17:58–65PubMed Haugen E, Nath KA (1999) The involvement of oxidative stress in the progression of renal injury. Blood Purif 17:58–65PubMed
21.
Zurück zum Zitat Klahr S (1997) Oxygen radicals and renal diseases. Miner Electrolyte Metab 23:140–143PubMed Klahr S (1997) Oxygen radicals and renal diseases. Miner Electrolyte Metab 23:140–143PubMed
22.
Zurück zum Zitat Shah SV (2001) Role of iron in progressive renal disease. Am J Kidney Dis 37:S30–S33PubMed Shah SV (2001) Role of iron in progressive renal disease. Am J Kidney Dis 37:S30–S33PubMed
23.
Zurück zum Zitat Nath KA, Croatt AJ, Haggard JJ, Grande JP (2000) Renal response to repetitive exposure to heme proteins: chronic injury induced by an acute insult. Kidney Int 57:2423–2433PubMed Nath KA, Croatt AJ, Haggard JJ, Grande JP (2000) Renal response to repetitive exposure to heme proteins: chronic injury induced by an acute insult. Kidney Int 57:2423–2433PubMed
24.
Zurück zum Zitat Johnson RJ, Couser WG, Chi EY, Adler S, Klebanoff SJ (1987) New mechanism for glomerular injury. Myeloperoxidase-hydrogen peroxide-halide system. J Clin Invest 79:1379–1387PubMedPubMedCentral Johnson RJ, Couser WG, Chi EY, Adler S, Klebanoff SJ (1987) New mechanism for glomerular injury. Myeloperoxidase-hydrogen peroxide-halide system. J Clin Invest 79:1379–1387PubMedPubMedCentral
25.
Zurück zum Zitat Gailit J, Colflesh D, Rabiner I, Simone J, Goligorsky MS (1993) Redistribution and dysfunction of integrins in cultured renal epithelial cells exposed to oxidative stress. Am J Physiol 264:F149–F157PubMed Gailit J, Colflesh D, Rabiner I, Simone J, Goligorsky MS (1993) Redistribution and dysfunction of integrins in cultured renal epithelial cells exposed to oxidative stress. Am J Physiol 264:F149–F157PubMed
26.
Zurück zum Zitat Shah SV (1988) Evidence suggesting a role for hydroxyl radical in passive Heymann nephritis in rats. Am J Physiol 254:F337–F344PubMed Shah SV (1988) Evidence suggesting a role for hydroxyl radical in passive Heymann nephritis in rats. Am J Physiol 254:F337–F344PubMed
27.
Zurück zum Zitat Alfrey AC, Froment DH, Hammond WS (1989) Role of iron in the tubulo-interstitial injury in nephrotoxic serum nephritis. Kidney Int 36:753–759PubMed Alfrey AC, Froment DH, Hammond WS (1989) Role of iron in the tubulo-interstitial injury in nephrotoxic serum nephritis. Kidney Int 36:753–759PubMed
28.
Zurück zum Zitat Nankivell BJ, Boadle RA, Harris DC (1992) Iron accumulation in human chronic renal disease. Am J Kidney Dis 20:580–584PubMed Nankivell BJ, Boadle RA, Harris DC (1992) Iron accumulation in human chronic renal disease. Am J Kidney Dis 20:580–584PubMed
29.
Zurück zum Zitat Sato K, Shiraki M (1998) Saccharated ferric oxide-induced osteomalacia in Japan: iron-induced osteopathy due to nephropathy. Endocr J 45:431–439PubMed Sato K, Shiraki M (1998) Saccharated ferric oxide-induced osteomalacia in Japan: iron-induced osteopathy due to nephropathy. Endocr J 45:431–439PubMed
30.
Zurück zum Zitat Boaz M, Smetana S, Weinstein T, Matas Z, Gafter U, Iaina A, Knecht A, Weissgarten Y, Brunner D, Fainaru M, Green MS (2000) Secondary prevention with antioxidants of cardiovascular disease in endstage renal disease (SPACE): randomised placebo-controlled trial. Lancet 356:1213–1218PubMed Boaz M, Smetana S, Weinstein T, Matas Z, Gafter U, Iaina A, Knecht A, Weissgarten Y, Brunner D, Fainaru M, Green MS (2000) Secondary prevention with antioxidants of cardiovascular disease in endstage renal disease (SPACE): randomised placebo-controlled trial. Lancet 356:1213–1218PubMed
31.
Zurück zum Zitat Tepel M, van der Giet M, Statz M, Jankowski J, Zidek W (2003) The antioxidant acetylcysteine reduces cardiovascular events in patients with end-stage renal failure: a randomized, controlled trial. Circulation 107:992–995PubMed Tepel M, van der Giet M, Statz M, Jankowski J, Zidek W (2003) The antioxidant acetylcysteine reduces cardiovascular events in patients with end-stage renal failure: a randomized, controlled trial. Circulation 107:992–995PubMed
32.
Zurück zum Zitat Kletzmayr J, Horl WH (2002) Iron overload and cardiovascular complications in dialysis patients. Nephrol Dial Transplant 17[Suppl 2]:25–29PubMed Kletzmayr J, Horl WH (2002) Iron overload and cardiovascular complications in dialysis patients. Nephrol Dial Transplant 17[Suppl 2]:25–29PubMed
33.
Zurück zum Zitat Kirk EA, Heinecke JW, LeBoeuf RC (2001) Iron overload diminishes atherosclerosis in apoE-deficient mice. J Clin Invest 107:1545–1553PubMedPubMedCentral Kirk EA, Heinecke JW, LeBoeuf RC (2001) Iron overload diminishes atherosclerosis in apoE-deficient mice. J Clin Invest 107:1545–1553PubMedPubMedCentral
34.
Zurück zum Zitat Stoves J, Inglis H, Newstead CG (2001) A randomized study of oral vs intravenous iron supplementation in patients with progressive renal insufficiency treated with erythropoietin. Nephrol Dial Transplant 16:967–974PubMed Stoves J, Inglis H, Newstead CG (2001) A randomized study of oral vs intravenous iron supplementation in patients with progressive renal insufficiency treated with erythropoietin. Nephrol Dial Transplant 16:967–974PubMed
35.
Zurück zum Zitat Aggarwal HK, Nand N, Singh S, Singh M, Hemant, Kaushik G (2003) Comparison of oral versus intravenous iron therapy in predialysis patients of chronic renal failure receiving recombinant human erythropoietin. J Assoc Physicians India 51:170–174PubMed Aggarwal HK, Nand N, Singh S, Singh M, Hemant, Kaushik G (2003) Comparison of oral versus intravenous iron therapy in predialysis patients of chronic renal failure receiving recombinant human erythropoietin. J Assoc Physicians India 51:170–174PubMed
36.
Zurück zum Zitat Charytan C, Qunibi W, Bailie GR (2005) Comparison of intravenous iron sucrose to oral iron in the treatment of anemic patients with chronic kidney disease not on dialysis. Nephron Clin Pract 100:c55–c62PubMed Charytan C, Qunibi W, Bailie GR (2005) Comparison of intravenous iron sucrose to oral iron in the treatment of anemic patients with chronic kidney disease not on dialysis. Nephron Clin Pract 100:c55–c62PubMed
37.
Zurück zum Zitat Van Wyck DB, Roppolo M, Martinez CO, Mazey RM, McMurray S; United States Iron Sucrose (Venofer) Clinical Trials Group (2005) A randomized, controlled trial comparing IV iron sucrose to oral iron in anemic patients with nondialysis-dependent CKD. Kidney Int 68:2846–2856PubMed Van Wyck DB, Roppolo M, Martinez CO, Mazey RM, McMurray S; United States Iron Sucrose (Venofer) Clinical Trials Group (2005) A randomized, controlled trial comparing IV iron sucrose to oral iron in anemic patients with nondialysis-dependent CKD. Kidney Int 68:2846–2856PubMed
38.
Zurück zum Zitat Agarwal R, Rizkala AR, Bastani B, Kaskas MO, Leehey DJ, Besarab A (2006) A randomized controlled trial of oral versus intravenous iron in chronic kidney disease. Am J Nephrol 26:445–454PubMed Agarwal R, Rizkala AR, Bastani B, Kaskas MO, Leehey DJ, Besarab A (2006) A randomized controlled trial of oral versus intravenous iron in chronic kidney disease. Am J Nephrol 26:445–454PubMed
39.
Zurück zum Zitat Agarwal R (2007) Nonhematological benefits of iron. Am J Nephrol 27:565–571PubMed Agarwal R (2007) Nonhematological benefits of iron. Am J Nephrol 27:565–571PubMed
40.
Zurück zum Zitat Singh AK, Szczech L, Tang KL, Barnhart H, Sapp S, Wolfson M, Reddan D; CHOIR Investigators (2006) Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med 355:2085–2098 Singh AK, Szczech L, Tang KL, Barnhart H, Sapp S, Wolfson M, Reddan D; CHOIR Investigators (2006) Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med 355:2085–2098
41.
Zurück zum Zitat Zager RA, Johnson AC, Hanson SY (2004) Parenteral iron therapy exacerbates experimental sepsis. Kidney Int 65:2108–2112PubMed Zager RA, Johnson AC, Hanson SY (2004) Parenteral iron therapy exacerbates experimental sepsis. Kidney Int 65:2108–2112PubMed
Metadaten
Titel
Iron, oxidative stress, and clinical outcomes
verfasst von
Rajiv Agarwal
Publikationsdatum
01.08.2008
Verlag
Springer Berlin Heidelberg
Erschienen in
Pediatric Nephrology / Ausgabe 8/2008
Print ISSN: 0931-041X
Elektronische ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-007-0673-1

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