Renal Innervation in Resistant Hypertension: A Review of Pathophysiology and Renal Denervation as Potential Treatment

Abstract

Background: Advances in treatment and increased awareness have improved the prognosis for many patients with hypertension (HTN). Resistant hypertension (RH) refers to a subset of hypertensive individuals who fail to achieve a desired blood pressure (BP) despite concurrent use of 3 different classes antihypertensive agents, one being a diuretic, and proper lifestyle changes. The prevalence and prognosis of RH are unclear owing to its heterogeneous etiologies, risk factors, and secondary comorbidities. Previous research has provided evidence that increased renal sympathetic nerve activity (RSNA) within the renal artery contributes to RH development. Renal denervation (RDN) is a procedure that attempts to ameliorate the effects of heightened RSNA via ablation renal sympathetic fibers. BP reductions associated with RDN may be attributed to decreased norepinephrine spillover, restoration of natriuresis, increasing renal blood flow, and lowering plasma renin activity. Early clinical trials perpetuated positive results, and enthusiasm grew exponentially. However, recent clinical trials have called into question RDN's efficacy. Numerous limitations must be addressed to discern the true effectiveness of RDN as a therapeutic option for RH.

Objective: We aimed to review the current understanding of RH, the anatomy of renal arteries, physiology of RH on renal arteries, anatomical pathways of the sympathetic involved in RH, RDN as a treatment option, and all relevant clinical trials treating RH with RDN.

Methods: We piloted a MEDLINE® database search of literature extending from 1980 to 2017, with emphasis on the previous five years, combining keywords such as "resistant hypertension" and "renal denervation."

Conclusion: A plethora of information is available regarding heightened RSNA leading to RH. RDN as a possible treatment option has shown a range of results. Reconciling RDN's true efficacy requires future trials to increased sites of nerve ablation, standardized protocol, increased anatomical understanding per individual basis, stricter guidelines regarding study design, increased operator experience, and integrating the use of a multielectrode catheter.

Keywords: Resistant hypertension; nerve ablation; renal artery; renal denervation; renal sympathetic nerve activity; stroke.