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Hypertension following erythropoiesis-stimulating agents (ESAs) in chronic kidney disease

Wajeh Y Qunibi, MD
William L Henrich, MD, MACP
Section Editors
Steve J Schwab, MD
George L Bakris, MD
Deputy Editor
Alice M Sheridan, MD


Hypertension is a common adverse effect of erythropoietin (EPO) treatment among patients with chronic kidney disease (CKD) and even among healthy subjects who receive erythropoietin [1-3]. Hypertension has also been described following the use of other erythropoiesis-stimulating agents (ESAs) in patients with CKD [4]. Among these patients, hypertension may developed de novo or may worsen after introducing ESAs. However, since hypertension in CKD patients may be due to several factors including volume overload, erythropoietin-related hypertension should be a diagnosis of exclusion.

This topic reviews hypertension related to erythropoietin among CKD patients. Other issues related to erythropoietin among CKD patients, including hemoglobin (Hb) targets, are addressed elsewhere. (See "Treatment of anemia in nondialysis chronic kidney disease" and "Hyporesponse to erythropoiesis-stimulating agents (ESAs) in chronic kidney disease" and "Treatment of anemia in hemodialysis patients".)


Overall, approximately 20 to 30 percent of patients who receive erythropoietin intravenously for the anemia of CKD develop an elevation in diastolic pressure of 10 mmHg or more [5,6]. A phase-III trial involving 251 hemodialysis patients found that 35 percent of patients developed an increase in their diastolic blood pressure (BP) of at least 10 mmHg or required an increase in their antihypertensive agents after three months of ESA therapy. Moreover, 44 percent of patients who were not hypertensive at baseline also had an increase in diastolic BP of at least 10 mmHg, and one-third of them were started on antihypertensive therapy [7].

Much of the evidence that ESAs contribute to hypertension in CKD patients was derived from a series of meta-analyses [6,8]. As an example, in one meta-analysis that included six randomized trials comparing erythropoietin versus placebo or no erythropoietin (n = 387 patients), patients who did not receive erythropoietin had a lower risk of hypertension (relative risk [RR] 0.50, 95% CI 0.33-0.76).

Another meta-analysis from the Cochrane Collaboration that included four controlled trials in nondialysis CKD patients showed a 26 percent higher risk of hypertension in erythropoietin-treated patients compared with no erythropoietin or placebo, but the effect was not statistically significant [9].

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Literature review current through: Sep 2017. | This topic last updated: Sep 18, 2017.
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