Proinflammatory effects of iron sucrose in chronic kidney disease

Kidney Int. 2006 Apr;69(7):1259-63. doi: 10.1038/sj.ki.5000164.

Abstract

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.

MeSH terms

  • Aged
  • Chemokine CCL2 / blood
  • Chemokine CCL2 / urine
  • Chronic Disease
  • Ferric Compounds / toxicity*
  • Ferric Oxide, Saccharated
  • Glucaric Acid
  • Humans
  • Inflammation / chemically induced*
  • Kidney Diseases / blood
  • Kidney Diseases / physiopathology*
  • Kidney Diseases / urine
  • Kidney Failure, Chronic / blood
  • Kidney Failure, Chronic / physiopathology*
  • Kidney Failure, Chronic / urine
  • Reproducibility of Results

Substances

  • CCL2 protein, human
  • Chemokine CCL2
  • Ferric Compounds
  • Ferric Oxide, Saccharated
  • Glucaric Acid