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

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 ≥ 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.

Effect of ferric carboxymaltose on serum phosphate and C-terminal FGF23 levels in non-dialysis chronic kidney disease patients: post-hoc analysis of a prospective study.

BACKGROUND: Some parenteral iron therapies have been found to be associated with hypophosphatemia. The mechanism of the decrease in serum phosphate is unknown. The aim of this study is to examine the effect of IV ferric carboxymaltose(FCM) on phosphate metabolism and FGF23 levels in patients with chronic kidney disease(CKD). METHODS: This is a post-hoc analysis of a prospective study carried out in 47 non-dialysis CKD patients with iron-deficiency anaemia who received a single 1000 mg injection of FCM. Markers of mineral metabolism (calcium, phosphate, 1,25-dihydroxyvitamin D, PTH and FGF23[c-terminal]) were measured prior to FCM administration and at week 3 and week 12 after FCM administration. Based on the measured levels of serum phosphate at week 3, patiens were classified as hypophosphatemic or non-hypophosphatemic. RESULTS: Serum phosphate levels decreased significantly three weeks after FCM administration and remained at lower levels at week 12 (4.24 ± 0.84 vs 3.69 ± 1.10 vs 3.83 ± 0.68 mg/dL, respectively, p < 0.0001. Serum calcium, PTH and 1,25-dihydroxyvitamin D did not change over the course of the study. Serum FGF23 decreased significantly from 442(44.9-4079.2) at baseline to 340(68.5-2603.3) at week 3 and 191.6(51.3-2465.9) RU/mL at week 12, p < 0.0001. Twelve patients were non-hypophosphatemic and 35 hypophosphatemic. FGF23 levels decreased in both groups, whereas no changes were documented in any of the other mineral parameters. CONCLUSIONS: In non-dialysis CKD patients, FCM induces reduction in serum phosphate levels that persists for three months. FCM causes a significant decrease in FGF23 levels without changes to other bone metabolism parameters.

Epidemiology of Fabry disease in patients in hemodialysis in the Madrid community.

This study screened for Fabry disease (FD) in patients in hemodialysis (HD) in the region of Madrid (CAM) with a cross-sectional design to evaluate HD-prevalent patients, followed by a three-year period prospective design to analyze HD-incident patients. INCLUSION CRITERIA: patients older than 18 years on HD in the CAM, excluding patients diagnosed with any other hereditary disease with renal involvement different from FD, that sign the Informed Consent (IC). EXCLUSION CRITERIA: underaged patients or not agreeing or not being capable of signing the IC. RESULTS: 3470 patients were included, 63% males and with an average age of 67.9±9.7 years. 2357 were HD-prevalent patients and 1113 HD-incident patients. For HD-prevalent patients, average time in HD was 45.2 months (SD 51.3), in HD-incident patients proteinuria was present in 28.4%. There were no statistical differences in plasmatic alpha-galactosidase A (α-GAL-A) activity or Lyso-GL-3 values when comparing HD-prevalent and HD-incident populations and neither between males and females. A genetic study was performed in 87 patients (2.5% of patients): 60 male patients with decreased enzymatic activity and 27 female patients either with a decreased GLA activity, increased Lyso-Gl3 levels or both. The genetic variants identified were: p.Asp313Tyr (4 patients), p.Arg220Gln (3 patients) and M290I (1 patient). None of the identified variants is pathogenic. CONCLUSIONS: 76% of HD Centers of the CAM participated in the study. This is the first publication to describe the prevalence of FD in the HD-population of a region of Spain as well as its average α-GAL-A-activity and plasmatic Lyso-Gl3 levels. It is also the first study that combines a cross-sectional design with a prospective follow-up design. This study has not identified any FD patient.

Posttransplant Lymphoproliferative Disease and Inhibitors of Mammalian Target of Rapamycin: When a Quick Look Back Can Change the Perspective.

Posttransplant lymphoproliferative disease represents a heterogeneous group of diseases characterized by uncontrolled proliferation of lymphocytes, favored by immunosuppression. Several risk factors for its development have been described, with Epstein-Barr virus infection being a main cause of early-onset forms and chronic antigen stimulation of donors and/or accumulated immunosuppression as key factors of later forms of lymphocyte transformation. The present clinical case presents a patient diagnosed with posttransplant lymphoproliferative disease 3 years after renal transplant who had a potentially lethal complication related to conversion to inhibitors of mammalian target of rapamycin. Because clinical studies that establish the most suitable treatment are lacking, it is recommended to identify the strategy, defining possible risks versus benefits of conversion to inhibitors of mammalian target of rapamycin in cases of posttransplant lymphoproliferative disease, and to maintain a high level of surveillance in case of possible secondary effects that can be verified after their introduction.

Acute and sub-acute effect of ferric carboxymaltose on inflammation and adhesion molecules in patients with predialysis chronic renal failure.

BACKGROUND: Treatment with parenteral iron causes oxidative stress, inflammation and endothelial dysfunction. Ferric carboxymaltose (FCM) is a new preparation of non-dextran iron which, due to its pharmacokinetics and stability, may induce less toxicity than other iron molecules. The aim of this study was to analyse the effect of FCM on inflammation and adhesion molecules in chronic kidney disease (CKD). METHODS: Forty-seven patients with predialysis CKD and iron-deficiency anaemia received a single dose of FCM (15 mg/kg, maximum dose 1 gram). At baseline and after 60 minutes (acute effect) and after 3 weeks and 3 months (sub-acute effect), we determined inflammatory markers: C-reactive protein (CRP), interleukin-6 (IL-6) and endothelial dysfunction: intercellular adhesion molecule (ICAM) and vascular adhesion molecule (VCAM). RESULTS: Treatment with FCM was associated with a significant increase in haemoglobin levels: 10 (0.7) vs. 11.4 (1.3)g/dl, p<.0001. CRP, IL-6, ICAM and VCAM levels did not correlate with baseline haemoglobin or ferritin levels and there was no relationship between changes in these markers and those of haemoglobin after administration of FCM. No significant, acute or sub-acute changes occurred in any of the inflammatory or endothelial markers studied. Statin therapy was associated with lower VCAM concentrations. CONCLUSIONS: Treatment with high doses of FCM in patients with predialysis CKD has no proinflammatory effect and does not alter levels of adhesion molecules ICAM and VCAM in this population.

¿Influye la vitamina D en los anticuerpos de superficie de la hepatitis B en pacientes no vacunados en hemodiálisis? / Does vitamin D influence hepatitis B surface antibodies in non-vaccinated patients on hemodialysis?

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