Conversion of darbepoetin to low doses of CERA maintains hemoglobin levels in non-dialysis chronic kidney disease patients.

BACKGROUND/AIMS: Finding the lowest effective dose of erythropoietin-stimulating agents is critical in the management of renal anemia. We evaluated the efficacy of converting darbepoetin to CERA at doses lower than those usually recommended. METHODS: We selected consecutive non-dialysis chronic kidney disease patients treated with darbepoetin doses ≤40 µg/week in absence of iron deficiency, recent blood transfusion, bleeding, neoplasia, myocardial infarction/stroke in the last 3 months. Darbepoetin ≤20 µg/week was shifted to CERA 75 µg/month, while darbepoetin 21-40 µg/week to CERA 100 µg/month. Primary endpoint was the change in hemoglobin (Hb goal, 11-13 g/dl) at month 3, 6, 9 and 12. RESULTS: Studied patients (n = 37) were aged 70 ± 13 years and GFR was 30 ± 12 ml/min/1.73 m(2); prevalence of males, diabetes and prior cardiovascular disease was 43, 45 and 40%, respectively. Before switching, efficacy population received darbepoetin 18 ± 10 µg/week with 28 patients receiving ≤20 µg/week. Prevalence of Hb goal at baseline was 75.7% and did not change at months 3 (70.3%), 6 (70.3%), 9 (72.2%), and 12 (80.0%). CERA dose remained unchanged during the study (81 ± 11, 82 ± 16, 91 ± 30, 90 ± 54 and 88 ± 61 µg/month). Out of the 438 visits performed, CERA dose was increased in 52 (11.9%) and reduced in 36 (8.2%) visits. Blood pressure, Hb, GFR, transferrin saturation and ferritin did not change. CONCLUSIONS: In chronic kidney disease patients treated with darbepoetin doses ≤40 µg/week, CERA can be efficaciously used at doses lower than those recommended.

Epoetin therapy and hemoglobin level variability in nondialysis patients with chronic kidney disease.

BACKGROUND AND OBJECTIVES: Intrapatient variability of hemoglobin (Hb) is a newly proposed determinant of adverse outcome in chronic kidney disease (CKD). We evaluated whether intensity of epoetin therapy affects Hb variability and renal survival in nondialysis CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We calculated the individual therapeutic index (TI) for epoetin (EPO; difference between rates of visits that required EPO dosage change and those with effective EPO change) from 1198 visits during the first year of EPO in 137 patients. Renal death was registered in the subsequent 18.1 mo. Analysis was made by TI tertile (lower, middle, and higher; i.e., from more to less intensive therapy). RESULTS: Main features and visit number were similar in tertiles. Lower Hb response to first EPO dosage was an independent predictor of higher TI (P = 0.002). The area under the curve for Hb (11.56 +/- 0.87, 11.46 +/- 1.20, and 10.95 +/- 1.48 g/dl per yr; P = 0.040) decreased from lower to higher tertile. Hb variability increased in parallel, as shown by the reduction of time with Hb at target (time in target, from 9.2 +/- 2.0 to 3.0 +/- 2.2 mo; P < 0.0001) and the wider values of within-patient Hb standard deviation (from 0.70 to 0.96; P = 0.005) and Hb fluctuations across target (P < 0.0001). In Cox analyses (hazard ratio [95% confidence interval]), risk for renal death was increased in the middle and higher tertiles (2.79 [1.36 to 5.73] and 2.94 [1.40 to 6.20]) and reduced by longer time in target (0.90 [0.83 to 0.98]). CONCLUSIONS: Lack of adjustment of EPO worsens Hb variability in CKD. Hb variability may be associated with renal survival, but further studies are needed to explore the association versus causal relationship.