ACE inhibitor and/or angiotensin receptor blocker therapy increased epoetin requirements.
Older age, elevated BMI, and use of ACE inhibitors and/or angiotensin receptor blockers (ARBs) are associated with increased epoetin requirements when normalizing blood hemoglobin levels in CKD patients.
In a post-hoc observational analysis (Nephrol Dial Transplant. 2007;22:794-800), Jerome Rossert, MD, of the Georges Pompidou European Hospital in Paris, and his colleagues identified factors associated with hyporesponsiveness to epoetin alfa in a group of 93 CKD patients treated to a high hemoglobin target (14-15 g/dL for men and 13-14 g/dL for women).
The study cohort was a group of patients from the Effect of early Correction of Anemia on the Progression of CKD (ECAP) study in which 390 patients with CKD were randomized to receive subcutaneous epoetin alfa to achieve a high (13-15 g/dL) or low (11-12 g/dL) target hemoglobin level.
All patients received subcutaneous epoetin once weekly at an initial dose of 25-100 IU/kg. Dose adjustments were permitted every four weeks as needed to achieve the target hemoglobin level, and the recommended increase in weekly epoetin dose was 25 IU/kg.
In the subgroup analysis, patients always treated with 100 IU/kg/week or less were defined as “responsive,” and patients requiring more than 100 IU/kg/week at any point during the four-month stabilization phase following the start of treatment were defined as “hyporesponsive.” Only patients in the high-hemoglobin target group were included in the subgroup analysis.
Of the 93 patients in the high hemoglobin group, 79 (85%) were epoetin responsive and 14 (15%) were hyporesponsive. The mean weekly epoetin dosage was 54.3 IU/kg in the responsive patients and 120.1 IU/kg in the hyporesponsive patients.
Use of an ACE inhibitor or ARB was documented in 64% of the hyporesponsive patients and 35% of the responsive patients. The mean BMI was 30.3 kg/m2 in the hyporesponsive group and 27.3 kg/m2 in the responsive group. The mean age of the hypo-responsive patients was 60.4 years compared with 56.2 years in the responsive patients. Epoetin dosage at the start of the maintenance phase was correlated with age, BMI, and measures of anemia. Weekly epoetin requirements during maintenance treatment were higher in patients with older age, higher BMI, and severe anemia.
After adjusting for demographic and disease-related factors and continuous covariates, unidentified patient characteristics accounted for 24% of the variance in the maintenance epoetin dose.