Proinflammatory effects of iron sucrose in chronic kidney disease.
Inflammation is a central component of progressive chronic kidney disease (CKD). Iron promotes oxidative stress and inflammatory response in animals and promotes progressive CKD. Parenteral iron provokes oxidative stress in patients with CKD; however, its potential to provoke an inflammatory response is unknown. In 20 veterans with CKD, 100 mg iron sucrose was administered intravenously over 5 min and urinary excretion rate and plasma concentration of monocyte chemoattractant protein-1 (MCP-1) were measured at timed intervals over 24 h. Patients were then randomized to placebo or N-acetyl cysteine (NAC) 600 mg b.i.d. and the experiment was repeated at 1 week. Iron sucrose markedly increased plasma concentration and urinary excretion rate of MCP-1 at baseline and at 1 week visits (P < 0.0001 for time effect). Urinary excretion peaked at 30 min and plasma concentration at 15 min. Plasma MCP-1 concentration fell from 164 +/- 17.7 to 135 +/- 17.7 pg/ml with NAC, whereas it remained unchanged from 133 +/- 12.5 to 132 +/- 17.7 pg/ml with placebo (P=0.001 for visit x antioxidant drug interaction). There was a reduction in MCP-1 urinary excretion rate from visit 1 to 2. At the baseline visit, the urinary excretion rate averaged 305 +/- 66 pg/min and at the second visit 245 +/- 67 pg/min (mean difference 60 +/- 28 pg/min, P = 0.030). There was no improvement in urinary MCP-1 excretion with NAC. In conclusion, iron sucrose causes rapid and transient generation and/or release of MCP-1 plasma concentration and increases urinary excretion rate, and systemic MCP-1 level but the urinary excretion rate is not abrogated with the antioxidant NAC. These results may have implications for the progression of CKD with parenteral iron.
Agarwal
R
R
Indiana University School of Medicine and Richard L Roudebush VA Medical Center, Indianapolis, Indiana 46202, USA. ragarwal@iupui.edu
D000368:Aged; D018932:Chemokine CCL2 / Q000097:blood / Q000652:urine; D002908:Chronic Disease; D005290:Ferric Compounds / Q000633:toxicity*; D000077605:Ferric Oxide, Saccharated; D005937:Glucaric Acid; D006801:Humans; D007249:Inflammation / Q000139:chemically induced*; D007674:Kidney Diseases / Q000097:blood / Q000503:physiopathology* / Q000652:urine; D007676:Kidney Failure, Chronic / Q000097:blood / Q000503:physiopathology* / Q000652:urine; D015203:Reproducibility of Results
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D005290:Ferric Compounds; D000077605:Ferric Oxide, Saccharated; D005937:Glucaric Acid