Pathophysiology of Cardio-Renal Syndrome: Autonomic Mechanisms

Sympathetic activation occurs in the setting of renal dysfunction and is associated with alterations of sensory afferent renal nerve activity with inputs into central autonomic nuclei responsible for cardiovascular control and sympathetic outflow. In disease states such as heart failure and renal failure, increased renal sympathetic nerve activity can further worsen renal function, with a shift from inhibitory to “less inhibitory” (or potentially excitatory) reflex responses. Available evidence suggests that in the setting of renal disease, the normally sympatho-inhibitory renal reflex shifts towards a sympatho-excitatory reflex. This shift may then contribute to the development and maintenance of cardio-renal syndrome and also to the sympathetic overactivation present in heart failure. Renal nerve denervation, with particular emphasis on the afferent renal nerves, could attenuate or abrogate these maladaptive responses in heart failure. The potential for renal nerves to reinnervate may significantly impact the long-term efficacy of this procedure. Definitive testing in long-term outcome studies in humans should inform the role that renal nerve denervation may play in heart failure and cardio-renal syndrome.