title: Oxidative stress markers in predicting response to treatment with ferric carboxymaltose in nondialysis chronic kidney disease patients.
abstract: BACKGROUND
  Nearly half of all non-dialysis chronic kidney disease (CKD) patients respond to iron therapy. Factors affecting anemia response to iron therapy are not well characterized. Oxidative stress (OS) is a recognized factor for anemia in CKD and promotes erythropoiesis stimulating agent (ESA) resistance; however, the influence in predicting response to intravenous (IV) iron has not been evaluated.
  
  
  METHODS
  Patients (n = 47) with non-dialysis CKD stages 3 - 5 (mean eGFR: 26 ± 10.4 mL/min/1.73 m2) and iron-deficiency anemia (hemoglobin < 11 g/dL, transferrin saturation (TSAT) index < 20%, and/or ferritin < 100 ng/mL) received a single injection of 1,000 mg of ferric carboxymaltose (FCM) and were observed for 12 weeks. Based on erythropoietic response (defined as â¥ 1 g/dL increase in hemoglobin level), patients were classified as responders or non-responders. Baseline conventional markers of iron status (TSAT and ferritin), inflammatory markers (C-reactive protein and IL-6), OS markers (oxidized LDL, protein carbonyl groups, erythrocyte superoxide dismutase, and glutathione peroxidase (GPx)), and catalase activity were measured.
  
  
  RESULTS
  FCM resulted in a significant increase in hemoglobin, TSAT, and ferritin (10 ± 0.7 vs. 11.4 ± 1.3 g/dL, p < 0.0001; 14.6 ± 6.4% vs. 28.9 ± 10%, p < 0.0001; 67.8 ± 61.7 vs. 502.5 ± 263.3 ng/dL, p < 0.0001, respectively). Responders and non-responders were 34 (72%) and 13 (28%), respectively. Age, baseline hemoglobin, estimated glomerular filtration rate, parathyroid hormone, and use of ESA or angiotensin-modulating agents were similar in both groups. Responders showed a tendency towards lower TSAT than non-responders (13.6 ± 6.5% vs. 17.2 ± 5.6%, p = 0.06) but similar ferritin levels. Inflammatory markers were similar in both groups. eGPx activity was lower in non-responders compared to responders (103.1 ± 50.9 vs. 144.9 ± 63.1 U/g Hb, p = 0.01, respectively), although the other proteins, lipid oxidation markers, and enzymatic antioxidants did not differ between the two groups. In the multivariate adjusted model, odds (95% CI) for achieving erythropoietic response to FCM were 10.53 (1.25 - 88.16) in the third tertile of eGPX activity and 3.20 (0.56 - 18.0) in the second tertile compared to those in the lowest tertiles (p = 0.02).
  
  
  CONCLUSIONS
  Decreased eGPx activity has adverse influences on response to FCM, suggesting that impaired erythrocyte antioxidant defense may be involved in the response to iron therapy in CKD patients.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Prats
authors.forename: Ramon
authors.initials: R
authors.lastname: Font
authors.forename: Carmen
authors.initials: C
authors.lastname: García
authors.forename: Mònica
authors.initials: M
authors.lastname: Muñoz-Cortés
authors.forename: Carmen
authors.initials: C
authors.lastname: Cabré
authors.forename: Manel
authors.initials: M
authors.lastname: Jariod
authors.forename: Marta
authors.initials: M
authors.lastname: Romeu
authors.forename: Montserrat
authors.initials: M
authors.lastname: Giralt
authors.forename: Alberto
authors.initials: A
authors.lastname: Martinez-Vea
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018798:Anemia, Iron-Deficiency / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood; D004334:Drug Administration Schedule; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D004920:Erythropoiesis / Q000187:drug effects*; D005260:Female; D005290:Ferric Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D005979:Glutathione Peroxidase / Q000097:blood; D006397:Hematinics / Q000008:administration & dosage / Q000627:therapeutic use*; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008320:Maltose / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D018384:Oxidative Stress; D011237:Predictive Value of Tests; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D005290:Ferric Compounds; D006397:Hematinics; D006454:Hemoglobins; C522335:ferric carboxymaltose; D008320:Maltose; D005979:Glutathione Peroxidase