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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.

SUBMITTER: Wilson AL

PROVIDER: S-EPMC7527543 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Wilson Anthony L AL Gandhi Jason J Suh Yiji Y Joshi Gunjan G Smith Noel L NL Khan Sardar Ali SA

Current hypertension reviews 20200101 2

<h4>Background</h4>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 co ...[more]

PMID: 30827252

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Project description:BACKGROUND:Adherence to medication has been repeatedly proposed to represent a major cause of treatment-resistant hypertension (TRH); however, treatment decisions such as treating TRH with renal denervation depend on accurate judgment of adherence. We carefully analyzed adherence rates to medication before and after renal denervation and its effect on blood pressure (BP) control. METHODS AND RESULTS:Eighty patients with TRH were included in 2 prospective observational studies that assessed the difference of potential antihypertensive and nephroprotective effects of renal denervation. To compare prescribed with actual medication intake (representing a measure of adherence), we analyzed urine samples collected at baseline and at 6 months after renal denervation for antihypertensive compounds or metabolites (by liquid chromatography-mass spectrometry). In addition to office BP, 24-hour ambulatory BP and central hemodynamics (central systolic pressure, central pulse pressure) were assessed. Informed consent for analyses of urine metabolites was obtained from 79 of 80 patients. Actual intake of all antihypertensive drugs was detected at baseline and at 6 months after renal denervation in 44 (56%) and 52 (66%) patients, respectively; 1 drug was missing in 22 (28%) and 17 (22%) patients, respectively, and ?2 drugs were missing in 13 (16%) and 10 (13%) patients, respectively. At baseline, 24-hour ambulatory BP (P=0.049) and central systolic BP (P=0.012) were higher in nonadherent patients. Adherence did not significantly change overall (McNemar-Bowker test, P=0.362). An increase in adherence was observed in 21 patients, and a decrease was observed in 11 patients. The decrease in 24-hour ambulatory BP was not different in those with stable adherence 6 months after renal denervation (n=41, -7±13 mm Hg) compared with those with increased adherence (n=21, -10±13 mm Hg) and decreased adherence (n=11, -7±14 mm Hg) (P>0.20). Our study is limited by the relatively small sample size and potentially by the specific health environment of our university center (Northern Bavaria, Germany). CONCLUSIONS:Nonadherence to medication among patients with TRH was relatively low: ?1 of 6 patients with TRH did not take ?2 of the prescribed drugs. Adherence pattern did not change significantly after renal denervation and had no impact on the overall observed BP changes, supporting the concept that renal denervation is an effective treatment in patients with TRH. CLINICAL TRIAL REGISTRATION:URL: https://www.clinicaltrials.gov. Unique identifiers: NCT00888433, NCT01442883 and NCT01687725.

Project description:Arterial hypertension is the most prevalent risk factor associated with increased cardiovascular morbidity and mortality. Although pharmacological treatment is generally well tolerated, 5%-20% of patients with hypertension are resistant to medical therapy, which is defined as blood pressure above goal (>140/90 mmHg in general; >130-139/80-85 mmHg in patients with diabetes mellitus; >130/80 mmHg in patients with chronic kidney disease) despite treatment with ?3 antihypertensive drugs of different classes, including a diuretic, at optimal doses. These patients are at significantly higher risk for cardiovascular events, in particular stroke, myocardial infarction, and heart failure, as compared with patients with nonresistant hypertension. The etiology of resistant hypertension is multifactorial and a number of risk factors have been identified. In addition, resistant hypertension might be due to secondary causes such as primary aldosteronism, chronic kidney disease, renal artery stenosis, or obstructive sleep apnea. To identify patients with resistant hypertension, the following must be excluded: pseudo-resistance, which might be due to nonadherence to medical treatment; white-coat effect; and inaccurate measurement technique. Activation of the sympathetic nervous system contributes to the development and maintenance of hypertension by increasing renal renin release, decreasing renal blood flow, and enhancing tubular sodium retention. Catheter-based renal denervation (RDN) is a novel technique specifically targeting renal sympathetic nerves. Clinical trials have demonstrated that RDN significantly reduces blood pressure in patients with resistant hypertension. Experimental studies and small clinical studies indicate that RDN might also have beneficial effects in other diseases and comorbidities, characterized by increased sympathetic activity, such as left ventricular hypertrophy, heart failure, metabolic syndrome and hyperinsulinemia, atrial fibrillation, obstructive sleep apnea, and chronic kidney disease. Further controlled studies are required to investigate the role of RDN beyond blood pressure control.

Dataset Information

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

Publications

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

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