Catheter-based afferent renal denervation as a treatment for hypertension

Abstract

Catheter-based total renal denervation is now FDA-approved for the treatment of hypertension, and the conventional theory behind its antihypertensive effects is through the ablation of efferent (sympathetic) renal nerves. Efferent renal nerves regulate long-term blood pressure and volume through renin release, sodium reabsorption, and renal vascular resistance. However, preclinical studies have shown that ablation of the sympathoexcitatory afferent (sensory) renal nerves can lower blood pressure to the same degree as total renal denervation in certain hypertensive rodent models. To further evaluate afferent renal denervation as a treatment for hypertension in humans, I repurposed the PeregrineTM catheter to perform catheter-based afferent renal denervation in sheep. I also generated preliminary data to show that catheter-based afferent renal denervation can lower blood pressure in hypertensive sheep. Furthermore, some patients do not have a blood pressure response to catheter-based total renal denervation, and there are no biomarkers to predict which patients would benefit most from this treatment. Our lab has been investigating the potential of urinary cytokines to indicate renal inflammation that drives afferent renal nerve overactivity and hypertension. Therefore, I collected urinary cytokine data from these hypertensive sheep and found that higher concentrations of certain urinary cytokines correlated with a greater blood pressure lowering effect after afferent renal nerve ablation. Lastly, studies showed that total renal denervation impairs blood pressure maintenance during sepsis and hemorrhage, and this is attributed to the loss of efferent renal nerves. Clinically, if a patient’s hypertension is driven by afferent renal nerves, then afferent renal denervation could lower their blood pressure while sparing efferent renal nerves. Therefore, I compared the effects of afferent versus total renal denervation in conscious rats on the hemodynamic response to sepsis and hemorrhage, but found that not all models rely on efferent renal nerves to regulate blood pressure. Hopefully, these contributions will lead to the safe and effective use of catheter-based afferent renal denervation to treat patients with hypertension and to the development of novel and effective treatments for other cardiometabolic diseases.