ABSTRACT: Resistance to erythropoiesis-stimulating agents (ESAs) is often associated with chronic inflammation. Here, we investigated how anaemia, ESA resistance and the plasma levels of biological markers of inflammation could influence all-cause and cardiovascular disease morbidity and mortality.
Seven hundred and fifty-three haemodialysis (HD) patients (mean age 66 ± 14.2 years, mean dialytic age 70 ± 77 months and diabetes 18.8%) were enrolled and followed-up for 36 months. Demographic, clinical and laboratory data, co-morbidity conditions, administered drugs, all-cause mortality and fatal/non-fatal cardiovascular (CV) events were recorded. We measured ESA resistance index, C-reactive protein (CRP) and interleukin-6 (IL-6).
Six hundred and fifty-one patients (86.4%) received ESAs. Patients with haemoglobin level <11 g/dL (n = 225) showed increased risk of CV [relative risk (RR) 1.415, 95% confidence interval (CI) 1.046-1.914] and overall mortality (RR 1.897, 95% CI 1.423-2.530) versus patients with haemoglobin levels >11 g/dL. ESA resistance values categorized into quartiles (Quartile I <5.6, Quartile II 5.7-9.6, Quartile III 9.7-15.4 and Quartile IV >15.4) correlated with all-cause mortality and fatal/non-fatal CV events (RR 1.97, 95% CI 1.392-2.786; RR 1.619, 95% CI 1.123-2.332, respectively). Furthermore, albumin was significantly reduced versus reference patients and correlated with all-cause mortality and CV events; CRP levels were higher in hyporesponders (Quartile IV) (P < 0.001) and predicted all-cause mortality and CV events. IL-6 but not CRP was a strong predictor of ESA resistance.
ESA responsiveness can be considered a strong prognostic factor in HD patients and seems to be tightly related to protein-energy wasting and inflammation.
Nephrology Dialysis Transplantation 02/2011; 26(8):2641-8. · 3.40 Impact Factor
ABSTRACT: Oxidative stress is prevalent in dialysis patients and has been implicated in the pathogenesis of cardiovascular disease and anemia. Vitamin E is a fat-soluble antioxidant that plays a central role in reducing lipid peroxidation and inhibiting the generation of reactive oxygen species. The aim of this cross-over randomized study was to compare the effects of a vitamin E-coated polysulfone (Vit E PS) membrane and a non-vitamin E-coated polysulfone (PS) membrane on inflammatory markers and resistance to erythropoietin-stimulating agents (ESAs).
After a 1-month run-in period of standard bicarbonate dialysis with a synthetic membrane, 62 patients of both genders, and older than 18 years, dialysis vintage 48 ± 27 months, BMI 22 ± 3 (from 13 different dialysis units) were randomized (A-B or B-A) in a cross-over design to Vit E PS (treatment A) and to PS (treatment B) both for 6 months. C-reactive protein (CRP) and interleukin-6 (IL-6) concentrations were determined by a sandwich enzyme immunoassay at baseline and every 2 months; red blood cell count, ESA dose and ESA resistance index (ERI) were assessed monthly.
Hemoglobin (Hb) levels significantly increased in the Vit E PS group from 11.1 ± 0.6 g/dl at baseline to 11.5 ± 0.7 at 6 months (p < 0.001) and remained unchanged in the PS group. Although ESA dosage remained stable during the observation periods in both groups, ERI was significantly reduced in the Vit E PS group from 10.3 ± 2.2 IU-dl/kg/g Hb week at baseline to 9.2 ± 1.7 at 6 months (p < 0.001). No significant variation of ERI was observed in the PS group. A significant reduction in plasma CRP and IL-6 levels was observed in the Vit E PS group: CRP from 6.7 ± 4.8 to 4.8 ± 2.2 mg/l (p < 0.001) and IL-6 from 12.1 ± 1.4 to 7.5 ± 0.4 pg/ml (p < 0.05). In the PS group, CRP varied from 6.2 ± 4.0 to 6.4 ± 3.7, and IL-6 from 10.6 ± 2.1 to 9.6 ± 3.5 (p = n.s.).
Treatment with Vit E PS membranes seems to lead to a reduction in ESA dosage in HD patients; in addition, a low chronic inflammatory response may contribute to a sparing effect on exogenous ESA requirements.
Blood Purification 01/2011; 32(1):7-14. · 2.10 Impact Factor
ABSTRACT: Previous studies reported significant increases in epoetin dosages when converting hemodialysis patients from subcutaneous (SC) to intravenous (IV) administration. More recent studies that corrected for iron deficiency found a much lower, if any, increase in epoetin dosage and/or decrease in hemoglobin (Hb) level after conversion from SC to IV epoetin administration. Therefore, the matter is still open for debate.
This multicenter observational study evaluated stable hemodialysis patients without iron deficiency who had a stable SC epoetin dosage and Hb level of 10 g/dL or greater (> or =100 g/L) at the time of study enrollment. Data for epoetin dosage, anemia, and inflammatory markers were collected retrospectively during the last 6 months of SC epoetin treatment and prospectively for 6 months after conversion to IV administration. The primary efficacy assessment was difference in Hb levels and epoetin dosages between patients administered epoetin SC and IV. Changes in values for iron stores, C-reactive protein, intact parathyroid hormone, and albumin were monitored as control parameters.
Data were analyzed for 262 hemodialysis patients from 6 Italian centers. Overall, mean Hb levels were similar with SC and IV epoetin administration (11.49 g/dL [114.9 g/L] and 11.44 g/dL [114.4 g/L]). Mean epoetin dosages also were similar with SC and IV administration (7,185 and 7,270 IU/wk). In patients requiring epoetin dosages of 12,000 IU/wk or greater at study entry, mean dosages tended to decrease after conversion to IV administration. There were no significant changes in control parameters.
Conversion from SC to IV epoetin administration did not result in changes in Hb levels or epoetin dosage requirements in iron-replete hemodialysis patients.
American Journal of Kidney Diseases 06/2006; 47(6):1027-35. · 5.43 Impact Factor