Moderator's view: renal denervation: the jury is still out and the verdict will be more complex than initially envisaged.

Abstract

New scientific findings and discoveriesthat may have an impactupon human health, particularly therapies for conditions thatdemand a high death toll, have a characteristic trajectory whendescribed in a graph relating the scientific proof of the validity/invalidity of the same research findings to the interest theyattract within the medical community and the public at large(Figure 1). Ideally, the two variables should maintain a linearassociation: the interest should grow in strict proportionality tothe strength of the scientific proof underlying the validity orinvalidity of the same findings. However, the two variables, thestrength of the scientific proof and the professional and publicinterest, have a polynomial rather than a linear relationship.Initially, discoveries are overlooked and the interest/scientificvalidity curve lies largely below the ideal, linear, relationship. Atsomestage,theinterestgrowsexponentiallyandtherelationshipcrosses the ideal line and the scientific discovery in questionbecomes overemphasized and fashionable or prematurelyaban-doned. At this point, scientific scrutiny becomes more stringentand, when the validity of the same discovery is well proven(or negated), the curve plateausand the interest inthe discoveryin question eventually becomes independent of the scientificproof underlying its value. This is the stage when the impli-cation of the discovery for human health is either definitivelyacceptedandtranslatedintoestablishedtreatmentsordismissedduetolackofvalue.Thistheoretical relationshipperfectlyservesthescopeofde-scribing the trajectory of renal denervation as a therapyfor treatment-resistant hypertension. Evidence that selectiverenal denervation delays the development and attenuates theseverity of hypertension was well documented in experimentalmodels in the early nineties [1], and in 1989, Esler et al. [2],the founder of renal denervation as a treatment for hyperten-sion, had already proved that efferent sympathetic nerveactivity was raised in human hypertension. Furthermore, inthe late nineties, Campese et al. [4] provided experimentalevidence that afferent sympathetic neurons transmit signals tothe central nervous system that contribute to setting the overallefferent sympathetic tone in renal injury [3] and renal failure.Although research on the sympathetic nervous system was amajor fruitful research area during these pioneer years, thepotential of renal denervation as a cure for human hyperten-sion was overlooked for nearly a decade. Mainly thanks towell-focused studies in a swine model by Esler’s group, renaldenervation was eventually developed as a minimally invasiveprocedure applicable in human studies. The procedure exploitsthe favorable location of the sympathetic fibers around therenal arteries and their peculiar sensitivity to radiofrequency.After the Simplicity-1 trial, interest in renal denervation lit-erally boomed and health systems in affluent countries includ-ing Australia, the country where this technique was founded,the Netherlands, Germany and Italy granted reimbursement