Erythropoietin-induced Hypertension in Chronic Kidney Disease-A Mechanistic Randomized Controlled Trial.

Abstract

Background: The mechanism of hypertension associated with erythropoiesis-stimulating agents in chronic kidney disease (CKD) is complex and remains poorly understood.

Methods: Here, anemic hypertensive patients with CKD and well-controlled or mildly elevated BP as confirmed by 24-hour ABP monitoring were randomly assigned to either a waitlisted group or darbepoetin in a 1:1 ratio stratified by stages of albuminuria. The primary end point was the change in 24-hour diastolic ABP from baseline to 12 weeks.

Results: We screened 1699 patients and randomized 27 patients of the planned 160. Mean age (SD) was 75 (8) years, mean hemoglobin 9.4 (0.6) g/dL, mean clinic BP 124.4 (19.5)/57.2 (11.4) mm Hg and was similar between groups. At 12 weeks there was 1.7 g/dL (95% CI, 0.9-2.5 g/dL) difference in hemoglobin between waitlisted and immediate start group. Within group change in diastolic 24-hour ABP in the waitlisted group was -1.91 mm Hg and the immediate start group was +1.07 mm Hg. The difference in the changes was 2.98 mm Hg (95% CI, -1.36 to 7.31), P = .18. Comparing SBP, endothelial function, and UACR in the waitlisted and immediate start groups showed no significant differences between groups. However, within the waitlisted group UACR increased 35% from baseline (95% CI, 11%-82%) with darbepoetin exposure. Cardiovascular and atherothrombotic serious adverse events were more frequent during darbepoetin exposure.

Conclusions: Among anemic CKD patients with reasonably controlled hypertension, exposure to darbepoetin did not change 24-hour ABP or endothelial function. However, increase in albuminuria and serious adverse events during exposure to darbepoetin is a cause for concern and requires larger studies to affirm or refute these observations.