Catheter-Based Renal Denervation in Uncontrolled and Resistant Hypertension: Evidence, Guidelines, Special Populations and Clinical Implementation.

Hypertension remains the leading modifiable cause of cardiovascular death, yet fewer than one in four treated adults achieves guideline-recommended blood pressure targets. Catheter-based renal denervation interrupts efferent and afferent renal sympathetic signalling and lowers blood pressure continuously and independently of medication adherence. After a decade of controversy following the neutral SYMPLICITY HTN-3 trial, a coherent body of second-generation sham-controlled randomised evidence, generated with radiofrequency, endovascular ultrasound, and perivascular alcohol platforms, has established a reproducible, modest, and durable antihypertensive effect with a favourable safety profile. Between 2024 and 2026, the field crossed three thresholds simultaneously: guideline endorsement on both sides of the Atlantic, including the first United States recommendation in the 2025 AHA/ACC guideline; a national coverage determination with coverage with evidence development; and the maturation of randomised and real-world follow-up to three years in cohorts exceeding 3000 patients. This state-of-the-art review synthesises the contemporary evidence base; quantifies the expected treatment effect and its heterogeneity; appraises safety across renal and vascular domains; examines emerging data in chronic kidney disease, diabetes, heart failure, and atrial fibrillation; and details the practical requirements for delivering renal denervation responsibly. We conclude by defining the research agenda that must now be addressed: the identification of responders, the development of an intraprocedural endpoint, a direct comparison with newly approved pharmacotherapy, and evidence of cardiovascular event reduction.