Table 1.

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.