Acute Cardiorenal Syndrome: Models and Heart-Kidney Connectors.

Cardiorenal syndrome type 1 (CRS-1) is an acute kidney injury (AKI) due to acute worsening of cardiac function. More than 20% of patients with acute heart failure develop AKI, and AKI predicts poor outcome. Although a number of potential pathways have been suggested as heart-kidney connectors which might drive the syndrome, there are significant barriers to investigation, such as a paucity of animal models, a lack of specific biomarkers, and an inconsistent temporal and causal relationship between changes in cardiac flow and development of renal dysfunction. Thus, mechanisms of heart-kidney interaction are still unclear, and there is no specific or effective therapy for CRS-1. This review, therefore, focuses on mitigating these challenges in the investigation of CRS-1. We review the available models and focus on mechanistic insights gained from those models. In particular, we focus on non-flow and endocrine mediators of CRS-1 such as heart-derived messengers which alter renal function and which may represent targetable pathways in this syndrome. As precise connectors of heart-kidney interaction remain unclear, the establishment of animal and relevant cell-culture models and further investigation are required.