Criticisms of clinical renal denervation (RDN) data to date
| Criticism | Problem | Potential solutions |
|---|---|---|
| Trial design | Non-blinded design Lack of sham control | Double-blind RDN versus sham procedure with best medical therapy10 |
| Patient selection and management | No per protocol exclusion of secondary causes of hypertension | Mandatory per protocol exclusion of secondary causes of hypertension |
| Ensure adherence to medication Per protocol managed lifestyle changes | Plasma/urine assay of medications/metabolites±directly observed therapy before qualifying BP measurement Optimal 24-h urinary sodium excretion | |
| Non-optimised antihypertensive medications Heterogeneity of patient suitability rates between RDN centres12 13 | Guidelines-based treatment regimens with add-on spironolactone and/or α-blockade Referral to hypertension specialist centres | |
| Ambulatory BP | Unnecessary inclusion of pseudoresistant patients with hypertension5 6 and potential overestimation of effect on office BP Less reduction in ambulatory BP parameters compared with office BP14 | Use of ambulatory BP as entry and outcome criteria15 16 |
| Human renal nerve anatomy uncertain Renovascular safety | Optimal sites for RDN yet to be defined Incomplete characterisation of renovascular injury periprocedurally and in the long term17 Reporting of only >60% stenoses6 No histological safety data from humans Requirement for concurrent, periprocedural antiplatelet therapy to be determined17 | Targeting of renal nerves depends also on energy modality used18 Further use of optical coherence tomography17 Postprocedure CT angiography or magnetic resonance angiography (MRA) at 6–12 months19 Further studies needed—may vary with energy modality used for RDN |
| Predictors of response Heterogeneity of BP response | Only baseline, office SBP reliably predicts response across studies5 6 20 Inability to distinguish between procedural failure or non-response Wide variation in response to RDN raises questions about role of renal nerves in hypertension21 | Autonomic function testing (where available) to be included in clinical studies and registries5 22 23 Research into ontable assessment of efficacy of RDN24 25 Research focusing on renal nerve physiology in hypertension and role of RDN26 27 |
| Durability of response and end points | 6-month office BP as primary end point5 6 20 | Major adverse events as primary end points |
| No data greater than 3 years post procedure published28 | Studies and registries to extend to several years |
BP, blood pressure; SBP, systolic BP.