Sodium ferric gluconate causes oxidative stress but not acute renal injury in patients with chronic kidney disease: a pilot study.
BACKGROUND
Intravenous (i.v) iron is widely used to treat anaemia in patients with chronic kidney disease (CKD). Although beneficial and usually well tolerated, concerns have been raised about its ability to cause oxidative stress and renal injury.


METHODS
To determine if i.v. iron causes oxidative stress [as assessed by plasma and urine malondialdehye (MDA)] and/or renal injury (as assessed by urinary albumin, total protein and enzymuria), we conducted a prospective, four-way randomized crossover, blinded end-point trial in eight patients with CKD. Two widely used doses of sodium ferric gluconate (125 mg infused over 1 h and 250 mg infused over 2 h) were given with or without the antioxidant N-acetylcysteine (NAC), resulting in four treatment dose-antioxidant/placebo combinations in each patient. Transferrin saturation was measured with urea polyacrylamide gel electrophoresis, MDA by high performance liquid chromatography, and albuminuria and proteinuria by standard clinical methods. Enzymuria was assessed by measurement of N-acetyl-beta-D-glucosaminidase (NAG) excretion by colorimetric assay.


RESULTS
I.v. ferric gluconate infusion at both doses resulted in a marked increase in transferrin saturation and a significant increase in plasma MDA levels. Urinary MDA levels also increased at the higher dose of iron. There was no evidence of acute renal injury, as assessed by albuminuria, proteinuria or enzymuria. Pre-treatment with NAC had no effect on oxidative stress or the above urinary parameters.


CONCLUSIONS
I.v. ferric gluconate caused oxidative stress (as reflected by increased MDA), but this was not associated with biochemical manifestations of acute renal injury.
Leehey
David J
DJ
Division of Nephrology, Department of Medicine, Loyola University School of Medicine and Edward Hines Jr VA Medical Center, Hines, IL 60141, USA. dleehey@lumc.edu
Palubiak
David J
DJ
Chebrolu
Srivasa
S
Agarwal
Rajiv
R
D000111:Acetylcysteine / Q000008:administration & dosage*; D058186:Acute Kidney Injury / Q000139:chemically induced / Q000453:epidemiology; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000740:Anemia / Q000188:drug therapy* / Q000209:etiology; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005290:Ferric Compounds / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D007262:Infusions, Intravenous; D007676:Kidney Failure, Chronic / Q000150:complications / Q000175:diagnosis; D007677:Kidney Function Tests; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D010865:Pilot Projects; D011336:Probability; D011379:Prognosis; D011446:Prospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D016037:Single-Blind Method
D005290:Ferric Compounds; D008315:Malondialdehyde; C035552:ferric gluconate; D000111:Acetylcysteine