Table 3

Research agenda to determine the role of renal denervation in clinical practice

Research priorityConsiderations
Pivotal studies and additional registry data to determine role of RDN in treatment of hypertension

  • It is critical to understand the effect of RDN in patients both on and off medications and given that current studies have been small in size, larger scale sham-controlled clinical trials (with powered endpoints) are needed with rigorous evaluation of medication usage.

  • Using ABP for endpoints is mandatory but office BP should also be collected and home BP where possible (with strict patient instructions to avoid using home BP data to adjust their medication regimens).

  • It may be difficult to recruit patients without the promise of a cross-over opportunity.

  • An outcome trial would be desirable, though there would be considerable challenges to achieving this and the cost would be enormous.

Establish the durability/safety of the different RDN technologies

  • Longer term follow-up to determine procedural, renal artery and renal safety is necessary as well as to determine durability of effect.

  • The possibility of functional renal nerve regrowth can be assessed.48

  • Are there differences between the energy modalities in terms of efficacy/safety/durability?

Is RDN cost-effective?

  • Modelling cost-effectiveness will require larger datasets and hopefully as these begin to emerge, the cost of the RDN procedure may have started to diminish due to market forces/competing technologies.

What is the mechanism of action?

  • This remains to be clarified and the role of afferent/efferent renal sympathetic signalling and selective afferent/efferent sympathectomy should be addressed.49

Which patients are best responders?

  • Heterogeneity of response is observed with all drug and device therapy—what does this mean and can true responders/non-responders be defined?

  • Even partial responders may benefit significantly from RDN if there are no other treatment options.

Can procedural markers of success be defined and will they be of value?

  • Novel technologies are providing insights into how to achieve successful ablation procedure through renal nerve mapping but presently add considerably to time spent on the table in the catheter lab and their value is undetermined.50

Of interest, not critical for hypertension indication
Is RDN useful for other sympathetically mediated diseases?

  • Conditions such as heart failure, obstructive sleep apnoea and chronic kidney disease are all characterised by increased sympathetic signalling and may respond to RDN.

Is lowering of BP the best biomarker of a successful RDN procedure?

  • If an RDN procedure does not lower BP by a clinically significant amount, it remains of interest to understand if there may be other benefits (eg, regression of LVH, improved glycaemic parameters, reduction in arterial stiffness).51–54

  • BP, blood pressure; LVH, left ventricular hypertrophy; RCT, randomised clinical trial; RDN, renal denervation.