title: Cardiorenal syndrome: pathophysiology and potential targets for clinical management.
abstract: Combined dysfunction of the heart and the kidneys, which can be associated with haemodynamic impairment, is classically referred to as cardiorenal syndrome (CRS). Cardiac pump failure with resulting volume retention by the kidneys, once thought to be the major pathophysiologic mechanism of CRS, is now considered to be only a part of a much more complicated phenomenon. Multiple body systems may contribute to the development of this pathologic constellation in an interconnected network of events. These events include heart failure (systolic or diastolic), atherosclerosis and endothelial cell dysfunction, uraemia and kidney failure, neurohormonal dysregulation, anaemia and iron disorders, mineral metabolic derangements including fibroblast growth factor 23, phosphorus and vitamin D disorders, and inflammatory pathways that may lead to malnutrition-inflammation-cachexia complex and protein-energy wasting. Hence, a pathophysiologically and clinically relevant classification of CRS based on the above components would be prudent. With the existing medical knowledge, it is almost impossible to identify where the process has started in any given patient. Rather, the events involved are closely interrelated, so that once the process starts at a particular point, other pathways of the network are potentially activated. Current therapies for CRS as well as ongoing studies are mostly focused on haemodynamic adjustments. The timely targeting of different components of this complex network, which may eventually lead to haemodynamic and vascular compromise and cause refractoriness to conventional treatments, seems necessary. Future studies should focus on interventions targeting these components.
authors.affiliation: Division of Nephrology, University of Michigan, 3914 Taubman Center, SPC 5364, 1500 E. Medical Center Drive, Ann Arbor, MI 48109, USA.
authors.forename: Parta
authors.initials: P
authors.lastname: Hatamizadeh
authors.forename: Gregg C
authors.initials: GC
authors.lastname: Fonarow
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Budoff
authors.forename: Sirous
authors.initials: S
authors.lastname: Darabian
authors.forename: Csaba P
authors.initials: CP
authors.lastname: Kovesdy
authors.forename: Kamyar
authors.initials: K
authors.lastname: Kalantar-Zadeh
mesh_terms: D059347:Cardio-Renal Syndrome / Q000453:epidemiology / Q000503:physiopathology* / Q000628:therapy*; D006321:Heart / Q000503:physiopathology*; D006801:Humans; D007668:Kidney / Q000503:physiopathology*; D012307:Risk Factors