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

Abstract

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. heart failure; renal failure; anemia; nitric oxide; reactive oxygen species COEXISTENCE OF RENAL AND cardiac disease is associated with high morbidity and mortality. This pathophysiological condition, in which combined cardiac and renal dysfunction amplifies a progression in the failure of the individual organ, has recently been denoted as severe cardiorenal syndrome (SCRS) (19,20).In patients with declined renal function measured by glomerular filtration rate (GFR), an independent increased risk for cardiovascular events has been found. The hazard ratio for cardiovascular events was 1.4 with a GFR Ͻ60 ml/min and increased with diminished renal function to 2.8 in patients with a GFR Ͻ30 ml/min (99). A 40% higher adjusted risk for adverse cardiovascular outcomes or death was observed in those with relatively minor degrees of renal dysfunction (120). The prevalence of chronic renal failure (CRF) is reportedly high in patients with congestive heart failure (CHF). Furthermore, the prevalence and severity of CRF correlate with the severity of CHF (44, 72). These data support that combined cardiac and renal failure is a profound problem, and a further understanding of the underlying pathophysiological and molecular mechanisms is needed to improve therapy.Our group proposed an interactive network of cardiorenal connectors, i.e., the renin-angiotensin system (RAS), nitric oxide and reactive oxygen species (NO-ROS) balance, the sympathetic nervous system (SNS), and inflammation, as the cornerstones of the pathophysiology o...

Recombinant human erythropoietin treatment protects the cardio-renal axis in a model of moderate chronic renal failure

“…23 Additionally, treatment with rhEPO has also been associated with hypertension. [24][25][26] Our results confirmed these conditions, with increased BP, together with tachycardia, peripheral sympathetic overactivity, and heart hypertrophy, in both the CRF and the rhEPO groups. However, the HR increase (tachycardia) in CRF rats was prevented in the group under rhEPO treatment, which might be due to a reduction of sympathetic overactivity, viewed by the prevention of NE and E increment in the left ventricle and in plasma.…”

Cardiorenal Syndrome

“…47 In cardiac cells, erythropoietin can prevent apoptosis and increase the number of cardiomyocytes. 48 Similar observations have been made in renal cells.…”

Cardiorenal Syndrome

“…Beneficial cardiorenal effects of exogenous erythropoietin have been demonstrated 36,37 by not only elevation of hemoglobin but also other nonhematopoietic actions, such as antiinflammatory, antioxidative, and antiapoptotic effects. 38,39 Exogenous erythropoietin has been reported to reduce cardiac fibrosis and hypertrophy in association with decreased B-type natriuretic peptide levels and to improve endothelial function. 39,40 However, overcorrection is associated with an increased risk of stroke, hypertension, vascular thrombosis, CV events, progression to ESRD, and death.…”