Mechanisms of Erythropoietin Action in the Cardiorenal Syndrome

Summary

Erythropoietin (EPO) treatment in patients with the severe cardiorenal syndrome increases cardiac performance and decreases progression of renal failure by dampening the main driving forces of the cardiorenal syndrome in part via non-erythropoietic pathways. I. Does EPO administration to patients with the severe cardiorenal syndrome increase cardiac performance and decrease progression of renal disease? II. Does EPO treatment affect the main driving forces of the cardiorenal connection, that is, dampen the activated renin-angiotensin system (RAS), attenuate increased reactive oxygen species (ROS), normalize increased sympathetic activity, and decrease inflammation? III. Does EPO treatment positively affect the cell function of patients with the cardiorenal syndrome: 1. are gene expression signatures of leukocytes positively influenced by EPO treatment, 2. does EPO shift the Jak/STAT pathway to a less pro-inflammatory profile in monocytes, and 3. are function and number of endothelial progenitor cells (EPCs) affected by treatment with EPO in the cardiorenal syndrome? IV. Can the direct actions of EPO be differentiated from the effects on hemoglobin levels?

Timeline

Start

2007-01

Primary completion

2011-07

Completion

2011-07

Publications

• Chung EY, Palmer SC, Saglimbene VM, Craig JC, Tonelli M, Strippoli GF. Erythropoiesis-stimulating agents for anaemia in adults with chronic kidney disease: a network meta-analysis. Cochrane Database Syst Rev. 2023 Feb 13;2(2):CD010590. doi: 10.1002/14651858.CD010590.pub3.
• Eisenga MF, Emans ME, van der Putten K, Cramer MJ, Diepenbroek A, Velthuis BK, Doevendans PA, Verhaar MC, Joles JA, Bakker SJL, Nolte IM, Braam B, Gaillard CAJM. Epoetin Beta and C-Terminal Fibroblast Growth Factor 23 in Patients With Chronic Heart Failure and Chronic Kidney Disease. J Am Heart Assoc. 2019 Aug 20;8(16):e011130. doi: 10.1161/JAHA.118.011130. Epub 2019 Aug 17.
• Emans ME, van der Putten K, Velthuis BK, de Vries JJ, Cramer MJ, America YG, Hillege HL, Meiss L, Doevendans PA, Braam B, Gaillard CA. Atherosclerotic renal artery stenosis is prevalent in cardiorenal patients but not associated with left ventricular function and myocardial fibrosis as assessed by cardiac magnetic resonance imaging. BMC Cardiovasc Disord. 2012 Sep 18;12:76. doi: 10.1186/1471-2261-12-76.
• van der Putten K, Jie KE, Emans ME, Verhaar MC, Joles JA, Cramer MJ, Velthuis BK, Meiss L, Kraaijenhagen RJ, Doevendans PA, Braam B, Gaillard CA. Erythropoietin treatment in patients with combined heart and renal failure: objectives and design of the EPOCARES study. J Nephrol. 2010 Jul-Aug;23(4):363-8.

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Indications