Renal nerves in physiology, pathophysiology and interoception

Sympathetic efferent renal nerves have key roles in the regulation of kidney function and blood pressure. Increased renal sympathetic nerve activity is thought to contribute to hypertension by promoting renal sodium retention, renin release and renal vasoconstriction. This hypothesis led to the development of catheter-based renal denervation (RDN) for the treatment of hypertension. Two RDN devices that ablate both efferent and afferent renal nerves received FDA approval for this indication in 2023. However, in animal models, selective ablation of afferent renal nerves resulted in comparable anti-hypertensive effects to ablation of efferent and afferent renal nerves and was associated with a reduction in sympathetic nerve activity. Selective afferent RDN also improved kidney function in a chronic kidney disease model. Notably, the beneficial effects of RDN extend beyond hypertension and chronic kidney disease to other clinical conditions that are associated with elevated sympathetic nerve activity, including heart failure and arrhythmia. These findings suggest that the kidney is an interoceptive organ, as increased renal sensory nerve activity modulates sympathetic activity to other organs. Future studies are needed to translate this knowledge into novel therapies for the treatment of hypertension and other cardiorenal diseases. Here, the authors discuss the roles of renal nerves and the effects of renal denervation in hypertension, chronic kidney disease, heart failure and arrhythmias. They suggest that interruption of afferent pathways that modulate sympathetic nervous system activity are likely to underlie some of the beneficial effects of renal denervation. Key points Activation of sympathetic efferent renal nerves, which relay information from the brain to the kidney, promotes renal sodium retention, renin release and renal vasoconstriction, which are thought to contribute to the development of hypertension. Sensory afferent renal nerves respond to physical and chemical changes in the kidney and relay information to the brain; whether specific nociceptive afferent renal nerves exist has not yet been determined. Catheter-based renal denervation (RDN), which ablates both afferent and efferent renal nerves, has been approved by the FDA as a treatment for hypertension. Preclinical and clinical studies have shown beneficial effects of RDN beyond blood pressure control in chronic kidney disease and other conditions that are associated with increased sympathe