Erythropoietin and the cardiorenal syndrome: cellular mechanisms on the cardiorenal connectors

Am J Physiol Renal Physiol. 2006 Nov;291(5):F932-44. doi: 10.1152/ajprenal.00200.2006. Epub 2006 Aug 1.


We have recently proposed severe cardiorenal syndrome (SCRS), in which cardiac and renal failure mutually amplify progressive failure of both organs. This frequent pathophysiological condition has an extremely poor prognosis. Interactions between inflammation, the renin-angiotensin system, the balance between the nitric oxide and reactive oxygen species and the sympathetic nervous system form the cardiorenal connectors and are cornerstones in the pathophysiology of SCRS. An absolute deficit of erythropoietin (Epo) and decreased sensitivity to Epo in this syndrome both contribute to the development of anemia, which is more pronounced than renal anemia in the absence of heart failure. Besides expression on erythroid progenitor cells, Epo receptors are present in the heart, kidney, and vascular system, in which activation results in antiapoptosis, proliferation, and possibly antioxidation and anti-inflammation. Interestingly, Epo can improve cardiac and renal function. We have therefore reviewed the literature with respect to Epo and the cardiorenal connectors. Indeed, there are indications that Epo can diminish inflammation, reduce renin-angiotensin system activity, and shift the nitric oxide and reactive oxygen species balance toward nitric oxide. Information about Epo and the sympathetic nervous system is scarce. This analysis underscores the relevance of a further understanding of clinical and cellular mechanisms underlying protective effects of Epo, because this will support better treatment of SCRS.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Erythropoietin / physiology*
  • Heart Failure / metabolism*
  • Heart Failure / physiopathology*
  • Humans
  • Kidney Failure, Chronic / metabolism*
  • Kidney Failure, Chronic / physiopathology*
  • Oxidative Stress


  • Erythropoietin