Can we predict the blood pressure response to renal denervation?

Abstract

Renal denervation (RDN) is a new therapy used to treat drug-resistant hypertension in the clinical setting. Published human trials show substantial inter-individual variability in the blood pressure (BP) response to RDN, even when technical aspects of the treatment are standardized as much as possible between patients. Widespread acceptance of RDN for treating hypertension will require accurate identification of patients likely to respond to RDN with a fall in BP that is clinically significant in magnitude, well-maintained over time and does not cause adverse consequences. In this paper we review and evaluate clinical studies that address possible predictors of the BP response to RDN. We conclude that only one generally reliable predictor has been identified to date, namely pre-RDN BP level, although there is some evidence for a few other factors. Experimental interventions in laboratory animals provide the opportunity to explore potential predictors that are difficult to investigate in human patients. Therefore we also describe results (from our lab and others) with RDN in spontaneously hypertensive rats. Since virtually all patients receiving RDN are taking three or more antihypertensive drugs, a particular focus of our work was on how ongoing antihypertensive drug treatment might alter the BP response to RDN. We conclude that patient age (or duration of hypertension) and concomitant treatment with certain drugs can affect the blood pressure response to RDN and that this information could help predict a favorable clinical response.

Keywords: Anti-hypertensive drugs; Hypertension; Renal nerves; Spontaneously hypertensive rat.

Figure 1

Mean arterial pressure (MAP) in 13 week old SHR subjected to bilateral renal denervation (RDX) or sham-operation (SHAM). Two weeks after surgery, rats were placed on a low salt diet (0.1% NaCl) for two weeks. MAP was significantly lower in the RDX rats from the time of RDX to the end of the study.

Figure 2

Mean arterial pressure (MAP) in rats subjected to surgical renal denervation (RDX) or sham operation (SHAM) during treatment with the centrally acting sympatholytic drug clonidine. MAP in the two groups was not significantly different on the last three days of clonidine treatment, but were significantly different on the last three days of the study.

Figure 3

Mean arterial pressure (MAP) in rats subjected to surgical renal denervation (RDX) or sham operation (SHAM) during treatment with the angiotensin type I receptor antagonist losartan. MAP in the two groups was significantly different during the last three days of losartan treatment, and during the last three days of the study.

Figure 4

Mean arterial pressure (MAP) in rats subjected to surgical renal denervation (RDX) during treatment with the beta-1 selective adrenergic receptor antagonist atenolol. MAP after RDX was significantly lower than during atenolol treatment alone only on the first two days after surgery.