Cardiorenal Syndrome and Heart Failure-Challenges and Opportunities

Abstract

Cardiorenal syndromes (CRS) describe concomitant bidirectional dysfunction of the heart and kidneys in which 1 organ initiates, perpetuates, and/or accelerates decline of the other. CRS are common in heart failure and universally portend worsened prognosis. Despite this heavy disease burden, the appropriate diagnosis and classification of CRS remains problematic. In addition to the hemodynamic drivers of decreased renal perfusion and increased renal vein pressure, induction of the renin-angiotensin-aldosterone system, stimulation of the sympathetic nervous system, disruption of balance between nitric oxide and reactive oxygen species, and inflammation are implicated in the pathogenesis of CRS. Medical therapy of heart failure including renin-angiotensin-aldosterone system inhibition and β-adrenergic blockade can blunt these deleterious processes. Renovascular disease can accelerate the progression of CRS. Volume overload and diuretic resistance are common and complicate the management of CRS. In heart failure and CRS being treated with diuretics, worsening creatinine is not associated with worsened outcome if clinical decongestion is achieved. Adjunctive therapy is often required in the management of volume overload in CRS, but evidence for these therapies is limited. Anemia and iron deficiency are importantly associated with CRS and might amplify decline of cardiac and renal function. End-stage cardiac and/or renal disease represents an especially poor prognosis with limited therapeutic options. Overall, worsening renal function is associated with significantly increased mortality. Despite progress in the area of CRS, there are still multiple pathophysiological and clinical aspects of CRS that need further research to eventually develop effective therapeutic options.

Figure 1.

A schematic depiction of the cardiorenal syndrome. Cardiac, renal, or systemic insults result in dysfunction of the heart and/or kidneys. Clocks are used to denote conditions that typically present chronically. The cardiorenal connectors mediate cross-talk between the heart and the kidneys, causing concomitant organ dysfunction. Cardiac dysfunction results in hemodynamic changes, which results in renal dysfunction. The consequences of cardiorenal syndrome include anemia, metabolic abnormalities, and volume overload. CKD, chronic kidney disease; CVP, central venous pressure; HF, heart failure; MAP, mean arterial pressure; RAAS, renin-angiotensin-aldosterone system; SNS, sympathetic nervous system.