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Oxidative stress markers in predicting response to treatment with ferric carboxymaltose in nondialysis chronic kidney disease patients.

AbstractBACKGROUND:
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 ≥ 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.
AuthorsMercedes Prats, Ramon Font, Carmen García, Mònica Muñoz-Cortés, Carmen Cabré, Manel Jariod, Marta Romeu, Montserrat Giralt, Alberto Martinez-Vea
JournalClinical nephrology (Clin Nephrol) Vol. 81 Issue 6 Pg. 419-26 (Jun 2014) ISSN: 0301-0430 [Print] Germany
PMID24691014 (Publication Type: Journal Article)
Chemical References
  • Biomarkers
  • Ferric Compounds
  • Hematinics
  • Hemoglobins
  • ferric carboxymaltose
  • Maltose
  • Glutathione Peroxidase
Topics
  • Adult
  • Aged
  • Aged, 80 and over
  • Anemia, Iron-Deficiency (blood, diagnosis, drug therapy)
  • Biomarkers (blood)
  • Drug Administration Schedule
  • Erythrocytes (drug effects, metabolism)
  • Erythropoiesis (drug effects)
  • Female
  • Ferric Compounds (administration & dosage, therapeutic use)
  • Glutathione Peroxidase (blood)
  • Hematinics (administration & dosage, therapeutic use)
  • Hemoglobins (metabolism)
  • Humans
  • Injections, Intravenous
  • Male
  • Maltose (administration & dosage, analogs & derivatives, therapeutic use)
  • Middle Aged
  • Multivariate Analysis
  • Odds Ratio
  • Oxidative Stress
  • Predictive Value of Tests
  • Renal Insufficiency, Chronic (blood, diagnosis, drug therapy)
  • Time Factors
  • Treatment Outcome

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