Renal Denervation for Uncontrolled Hypertension: A Measurement-First, Program-Based Approach

Background/Objectives: Renal denervation (RDN) has re-emerged as an adjunctive treatment option for patients with uncontrolled or resistant hypertension, with contemporary sham-controlled trials showing a modest but reproducible reduction in out-of-office blood pressure. However, in routine practice, apparent treatment resistance often reflects pseudoresistance caused by the white-coat effect, poor measurement quality, therapeutic inertia, or nonadherence. This review aimed to summarize the contemporary evidence on renal denervation in uncontrolled or resistant hypertension and to propose a pragmatic, measurement-first framework for patient selection, integration into routine care, and a structured post-procedural response assessment. Methods: This article is a narrative, implementation-focused review. A structured search of PubMed, Embase, Cochrane CENTRAL, and Web of Science was performed from database inception through January 2026. We prioritized the randomized sham-controlled RDN trials, major meta-analyses, guidelines, consensus documents, and studies addressing ABPM, HBPM, medication adherence, and telemonitoring. Results: The contemporary sham-controlled trials support RDN as an adjunctive option with a modest blood pressure-lowering effect, which is best assessed by out-of-office measurements. The placebo-adjusted reductions in ambulatory systolic blood pressure were generally in the 4–6 mmHg range. Appropriate use requires the confirmation of sustained uncontrolled hypertension, the exclusion of pseudoresistance, the optimization of treatment, and an adherence assessment. We identified three phenotypes most likely to benefit and proposed a three-axis framework for a response assessment at 3 and 6 months. Conclusions: RDN should be viewed not as a substitute for antihypertensive therapy but as a program-based adjunct for carefully selected patients. The measurement-first care pathway presented here should be interpreted as a pragmatic clinical model intended to operationalize the available trial and guideline evidence in routine care, rather than as a prospectively validated algorithm or formal consensus recommendation.