Pathogenetic Pathways of Cardiorenal Syndrome and their Possible Therapeutic Implications

Background: Cardiorenal syndrome (CRS) is the term used to describe a complex disorder of the heart and kidneys, in which acute or chronic dysfunction of one organ initiates and perpetuates disease in the other. CRS is recognized as an important clinical condition that is increasingly becoming a major public health problem due to the high associated morbidity and mortality rates. Methods: This review discusses current understanding of the pathogenetic pathways involved in CRS and future therapeutic implications of such pathways for patients. Results: Multiple pathophysiological pathways are implicated in CRS, complicating the pathogenic features of this disease. Regarding hemodynamic factors, accumulating evidence now suggests that the importance of renal blood flow reduction as a mediator of CRS is limited and that increased venous pressure seems to be more crucial. Other non-hemodynamic mechanisms such as the renin-angiotensin system, sympathetic nervous system, oxidative stress, inflammation, anemia, and obesity have also been implicated in the pathogenesis of CRS and could play important roles in the clinical disease course. It is likely that several of these mechanisms operate simultaneously and that the relative importance of each mechanism differs among patients and clinical situations. However, despite the growing bank of experimental and clinical data, knowledge about the underlying pathophysiology of CRS remains limited as do the current therapeutic options. Conclusion: CRS is an important clinical condition that can be complicated by multiple pathophysiological mechanisms. Consequently, the underlying pathophysiology of CRS remains ill-defined and current therapeutic options for CRS patients have limitations. Ongoing studies and the emerging research fields such as epigenetics are expected to reconcile the multiple pathogenetic pathways at play in CRS and lead to the development of novel and more effective therapeutic approaches.