Proteomic Biomarkers in the Cardiorenal Syndrome: Toward Deciphering Molecular Pathophysiology

Abstract Cardiorenal syndrome (CRS) is defined by coexisting heart and renal dysfunctions. Malfunction of 1 organ may cause dysfunction of the other with variable causative disease that defines the type of CRS (1–5). Numerous studies showed that the prevalence of cardiovascular disease is increased in patients with chronic kidney disease (CKD). Similarly, CKD affects a large proportion of patients with heart failure. This overlap between primary heart or primary kidney disease blurs cause–effect inferences of the initiator/target organ. The classical subdivision of CRS in 5 categories does not provide pathophysiological suggestions for targeted intervention. It seems timely to revisit the value of CRS biomarkers in a pathophysiology-centered approach. We systematically reviewed the literature in CRS, which revealed 53 clinical studies describing the use of 44 biomarkers and 4 proteomic panels. All biomarkers are involved in at least one of the CRS comorbidities. Among the pathways affected, inflammation, aberrant glucose metabolism, neurohormonal activation, and oxidative stress are well described. There is growing evidence that fibrosis may be the “cornerstone” that unifies most of the pathways leading to CRS. Formation of excess fibrous connective tissue antedates CRS in many cases. This review highlights that biomarkers reflecting fibrosis may be of substantial clinical value in the early detection, prognostication, and guiding treatment of CRS. Biomarkers detecting changes in collagen turnover in the extracellular matrix of heart and kidney appear able to depict subclinical changes in the fibrotic remodeling of tissues and constitute a promising approach toward personalized intervention in CRS.