Randomized clinical trial on acute effects of i.v. iron sucrose during haemodialysis.
OBJECTIVE
Haemodialysis induces endothelial dysfunction by oxidation and inflammation. Intravenous iron administration during haemodialysis could worsen endothelial dysfunction. The aim of this study was to ascertain if iron produces endothelial dysfunction and the possible neutralizing effect of N-acetylcysteine when infused before iron. The oxidative and inflammatory effects of iron during haemodialysis were also assessed.


METHODS
Forty patients undergoing haemodialysis were studied in a randomized and cross-over design with and without N-acetylcysteine infused before iron sucrose (50 or 100 mg). Plasma Von Willebrand factor (vWF), soluble intercellular adhesion molecule-1 (sICAM-1) levels, malondialdehyde, total antioxidant capacity, CD11b/CD18 expression in monocytes, interleukin (IL)-8 in monocytes and plasma IL-8 were studied at baseline and during haemodialysis.


RESULTS
Haemodialysis produced significant (P < 0.001) increase in plasma vWF, sICAM-1, malondialdehyde, IL-8 and CD11b/CD18 expression in monocytes, as well as decrease in total antioxidant capacity. Iron induced significant increase in plasma malondialdehyde and IL-8 in monocytes, but had no effect on total antioxidant capacity, CD11b/CD18 expression, plasma IL-8, vWF and sICAM-1. The addition of N-acetylcysteine to 50 mg of iron produced a significant (P = 0.040) decrease in malondialdehyde.


CONCLUSIONS
Standard (100 mg) and low (50 mg) doses of iron during haemodialysis had no effects on endothelium. Iron only had minor effects on inflammation and produced an increase in oxidative stress, which was neutralized by N-acetylcysteine at low iron dose. Haemodialysis caused a significant increase in oxidative stress, inflammation and endothelial dysfunction markers.
Garcia-Fernandez
Nuria
N
Department of Nephrology, Clinic of the University of Navarra, Pamplona, Spain. nrgarcia@unav.es
Echeverria
Aitziber
A
Sanchez-Ibarrola
Alfonso
A
Páramo
José Antonio
JA
Coma-Canella
Isabel
I
D000111:Acetylcysteine / Q000008:administration & dosage; D000368:Aged; D000975:Antioxidants / Q000008:administration & dosage; D015415:Biomarkers / Q000097:blood; D039481:CD11b Antigen / Q000097:blood; D018821:CD18 Antigens / Q000097:blood; D018592:Cross-Over Studies; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D005260:Female; D005290:Ferric Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D000077605:Ferric Oxide, Saccharated; D005937:Glucaric Acid; D006397:Hematinics; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000097:blood; D007262:Infusions, Intravenous; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D011446:Prospective Studies; D006435:Renal Dialysis / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome; D014841:von Willebrand Factor / Q000378:metabolism
D000975:Antioxidants; D015415:Biomarkers; D039481:CD11b Antigen; D018821:CD18 Antigens; C508606:CXCL8 protein, human; D005290:Ferric Compounds; D006397:Hematinics; C509295:ITGAM protein, human; D018836:Inflammation Mediators; D016209:Interleukin-8; D014841:von Willebrand Factor; D018799:Intercellular Adhesion Molecule-1; D008315:Malondialdehyde; D000077605:Ferric Oxide, Saccharated; D005937:Glucaric Acid; D000111:Acetylcysteine