The progressive cardiorenal syndrome in heart failure: mechanisms and therapeutic insights.

The cardiorenal syndrome refers to the interdependence of cardiocirculatory aberrations and renal dysfunction that signify a worsening in heart failure outcome. Biochemically, it appears covertly as an abnormality in renal function and when progressive, is manifested by symptom exacerbation and worsening renal impairment during application of therapy to ameliorate such symptoms. The pathways leading to these distinct impairments involve not only hemodynamic deterioration but also neurohormonal, inflammatory, and intrinsic renal mechanisms that produce this syndrome. Traditional therapy with diuretics typically worsens the cardiorenal syndrome, and vasodilator or inotropic therapy has not been shown to help either. New therapeutic avenues involving vasopressin antagonists, adenosine antagonists, and ultrafiltration are being investigated. In the absence of underlying primary renal parenchymal disease, mechanical ventricular assist devices or cardiac transplantation achieve reversal of the progressive cardiorenal syndrome, indicating the sentinel role of interrupting the cardiocirculatory aberrations that accompany this clinical manifestation.