Impact of Renal Pelvic Denervation on Systemic Hemodynamics and Neurohumoral Changes in a Porcine Model

Abstract

<b><i>Introduction:</i></b> The blood pressure (BP) response to arterial renal denervation (RDN) is variable. <b><i>Methods:</i></b> This study examined the effectiveness of renal pelvic denervation (RPD) on BP, heart rate (HR), norepinephrine (NE), and histopathology in 42 swine. NE levels were measured immediately, 7, 14, 30, and 90 days after RPD. Intra-arterial BP and HR were measured throughout RPD and after 14 days in 5 swine. <b><i>Results:</i></b> During the procedure, RPD immediately reduced systolic BP (−20.6 ± 18.3 mm Hg), diastolic BP (−6.0 ± 8.3 mm Hg), and HR (−5.4 ± 5.6 bpm), which remained decreased at follow-up. The porcine kidneys had a mean NE reduction of 76% directly post procedure and 60% after 7 days, 64% after 14 days, 57% after 30 days, and 65% after 90 days. Histopathological examination confirmed nerve ablation. <b><i>Conclusions:</i></b> These preliminary findings suggest that the renal pelvis nerve ablation is an encouraging target for RDN. Clinical trials are required to test the feasibility of RPD in human hypertension.

Durability of the Blood Pressure Effects of Renal Pelvic Denervation in Patients with Hypertension during a 12-Month Observation

“…Perhaps the most remarkable observation by our office measurements was a reduction in blood pressure just 1 day after the ablation procedure. This finding is consistent with our preclinical denervation studies in the pig that demonstrated very rapid blood pressure reductions together with evidence for reduced sympathetic activity in the kidneys [8]. It is interesting that this blood pressure effect increased further during the month following the procedure, consistent with the hypothesis that ablation of the renal afferent fibers that go to the central nervous system can result, over time, in the decreased systemic sympathetic activity observed in long-term follow-up studies of patients treated with renal nerve ablation [13].…”

“…There was a modest but significant sustained reduction in serum creatinine and an increase in estimated glomerular filtration rate, thus providing reassurance that the renal pelvic denervation procedure did not adversely affect renal function. The mechanism for this apparently beneficial effect is not clear but may at least partly depend upon intra-renal vasodilation resulting from the reduction in renal sympathetic activity produced by renal pelvic denervation [8]. It will be important to further study kidney function in larger cohorts during long-term follow-ups in the future.…”

“…Instead, based on commonly performed urology procedures, ureteral sheaths are placed in the ureters and wire electrodes are passed through the sheaths to apply radiofrequency energy to the pelvis of the kidney where renal sympathetic fibers are concentrated. The physiologic and anatomic feasibility of this approach have been based on observations in the pig that demonstrated histopathological and hemodynamic evidence to support this approach [8]. Subsequently, we performed a feasibility study that demonstrated procedural and clinical safety as well as significant blood pressure reductions at the primary study endpoint 2 months after the denervation procedure [9].…”

Transurethral Renal Pelvic Denervation: A Feasibility Trial in Patients with Uncontrolled Hypertension

“…The early BP reduction achieved with renal pelvic denervation observed in the present study is consistent with our preclinical studies in a porcine model that reported meaningful BP reductions within hours of denervation that were associated with substantial reductions in renal tissue norepinephrine concentrations. 11 And although we cannot exclude the possibility that variable medication adherence by patients might partly explain the observed changes in BP, it is a reasonable speculation that the continuing reductions observed in office BP by the 2-month primary endpoint may reflect the contribution of afferent renal nerve fiber ablation. Such an effect has been considered previously in renal denervation studies as an explanation for delayed BP effects that presumably reflected central adaptations of sympathetic outflow caused by diminished renal afferent input.…”

“…Applying radiofrequency energy from inside the renal pelvis has been shown in a porcine model to reduce BP and renal tissue norepinephrine levels. 11 A preliminary pilot experience using this approach in a very small group of hypertensive patients also suggested its clinical potential. 12 This current study assessed the clinical feasibility of renal pelvic denervation in a cohort of patients with uncontrolled hypertension despite the prescription of antihypertensive drugs.…”