J Cachexia Sarcopenia Muscle (2011) 2:135–142 DOI 10.1007/s13539-011-0038-2 REVIEW Cardio-renal cachexia syndromes (CRCS): pathophysiological foundations of a vicious pathological circle Mariantonietta Cicoira & Stefan D. Anker & Claudio Ronco Received: 27 May 2011 / Accepted: 5 August 2011 / Published online: 24 August 2011 # The Author(s) 2011. This article is published with open access at Springerlink.com Abstract Cardio-renal syndromes (CRS) are defined as disorders of the heart and kidney whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other. CRS have been classified into five categories, where types 2 and 4 represent respectively chronic cardio-renal and chronic reno-cardiac syndromes. In these conditions, the chronic disorder of either the heart or kidney has been shown to induce some degree of cachexia. At the same time, cachexia has been proposed as a possible mechanism contributing to the worsening of such pathological organ cross talk. Common pathogenetic mechanisms underlie body wasting in cachectic states of different chronic heart and kidney diseases. In these circumstances, a vicious circle could arise, in which cachexia associated with either heart failure or chronic kidney disease may contribute to further damage of the other organ. In chronic CRS, activation of the immune and neuroendocrine systems contributes to the genesis of cachexia, which in turn can negatively affect the heart and kidney function. In patients with cardiac sustained activa- tion of the immune and neuroendocrine systems and M. Cicoira (*) Department of Medicine, Section of Cardiology, University of Verona, Verona, Italy e-mail: mariantonietta.cicoira@univr.it S. D. Anker Applied Cachexia Research, Department of Cardiology, Charité Medical School, Campus Virchow-Klinikum, Berlin, Germany C. Ronco Department of Nephrology Dialysis & Transplantation, International Renal Research Institute (IRRIV), San Bortolo Hospital, Vicenza, Italy oxidative stress, renal vascular resistance can increase and therefore impair renal perfusion, leading to worsening kidney function. Similarly, in renal cachexia, increased levels of pro-inflammatory cytokines can cause progressive left ventricular systolic dysfunction, myocardial cell death, endothelial dysfunction and increased myocardial fibrosis, with consequent impairment of the chronic reno-cardiac syndrome type 4. Thus, we speculate that the occurrence of different types of chronic CRS could represent a funda- mental step in the genesis of cachexia, being renal and cardiac dysfunction closely related to the occurrence of systemic disorders leading to a final common pathway. Therefore, the heart and kidney and cachexia represent a triad causing a vicious circle that increases mortality and morbidity: In such circumstances, we may plausibly talk about cardio-renal cachexia syndrome. Complex interrela- tions may explain the transition from CRS to cachexia and from cachexia to CRS. Identification of the exact mecha- nisms occurring in these conditions could potentially help in preventing and treating this deadly combination. Keywords Cardio-renal syndromes . Heart . Kidney 1 Introduction Heart failure (HF) is a clinical condition associated with poor prognosis and high hospitalisation rates due to exacerbation of the disease [1, 2]. Concomitant kidney abnormalities are frequent: Only 7% of chronic HF patients have a preserved kidney function, with the majority of patients having mild to moderate impairment of glomerular filtration rate [3]. Furthermore, acute HF syndromes are frequently complicated by acute kidney injury (AKI) [4]. In both chronic and acute settings of HF, many studies have