Table 1

Criticisms of clinical renal denervation (RDN) data to date

CriticismProblemPotential solutions
Trial designNon-blinded design
Lack of sham control
Double-blind RDN versus sham procedure with best medical therapy10
Patient selection and managementNo per protocol exclusion of secondary causes of hypertensionMandatory 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 BPUnnecessary 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 points6-month office BP as primary end point5 6 20Major adverse events as primary end points
No data greater than 3 years post procedure published28Studies and registries to extend to several years
  • BP, blood pressure; SBP, systolic BP.