NephroBlate™ Renal Denervation System: Urologic-Nephrologic Based Approach to Resistant Hypertension

Abstract

Aims

To evaluate in a preclinical model, and limited clinical series, the utility of a monopolar electrode catheter, NephroBlate™ renal denervation device (Verve Medical, Peoria, Arizona) delivering radio-frequency (RF) energy placed into the renal pelvis in order to treat resistant hypertension (RH). We also describe our first clinical applications of this system, first in patients prior to nephrectomy, as well as in a small pilot clinical study in hypertensive resistant patients.

Methods and Results

Sixteen female domestic swine weighing 60–65 kg underwent renal pelvic denervation via ureteral access. The animals were euthanized, some immediately after delivery of RF energy, the others were euthanized 7 days, 14 days, and 30 days after ablation. Sixteen other female domestic swine weighing 60–65 kg, were used as control. They were euthanized at different intervals similar to the animals treated with RF energy. Renal cortical tissue was harvested for determination of tissue Norepinephrine (NE) by High Performance Liquid Chromatography (HPLC). Histopathology of the treated zone (the renal pelvis and adjacent sympathetic nerves) was performed to assess and confirm nerve damage. There was significant reduction in the NE levels, the mean reduction was 57 % in the RF treated animals compared to the control sample. Histopathology confirmed nerve ablation in the treated zone in the animals treated with RF energy.

With these results, we developed a protocol to treat a small number of patients (n = 3, four kidneys) with chronic kidney disease undergoing elective unilateral or bilateral nephrectomy for various etiologies, at Muljibhai Patel Urological Hospital in Nadiad, India. RF catheter was introduced via trans-urethral approach into the renal pelvis, and RF energy was administered across the hilar wall of the renal pelvis. One patient was pre-renal transplant and had both kidneys treated. One week after administration of the RF energy treatment with the NephroBlate™ device, the previously planned nephrectomy was performed. Histopathology of the treated zone was performed and hilar sympathetic denervation was confirmed in the treated zone compared to the untreated zone of the hilum.

With these results, we developed our clinical protocol to assess the utility of our device for the treatment of patients with resistant hypertension. In our study, the inclusion criteria included: office systolic blood pressure (SBP ≥160 mmHg) (SBP ≥ 150 mmHg with Type II diabetes mellitus), on >2 antihypertensive agents. Four patients were treated with RF energy administered to each kidney across the renal pelvis. As in the diseased kidney study, the procedure was done under general anesthesia. In neither study, did patients receive aspirin, heparin or any anti-platelet agents. Within minutes of treatment of the first kidney, a significant blood pressure drop was noted immediately in the OR (Systolic mean 44 mm; Diastolic mean 13 mm) which persisted for at least 3 months during follow up. No apparent complications were noted in either group.

Conclusions

In this small series of humans treated with the NephroBlate™ RF energy device with limited follow-up, we see a promising nonvascular alternative for renal denervation for the treatment of resistant hypertension. If the limited clinical experience safety and efficacy demonstrated above, can be confirmed in a larger scale study, this approach may offer an alternative RF renal denervation option for patients who cannot be treated with the standard percutaneous arterial devices.