Prairie Renal Denervation Study

Study design and patients:

This study will be conducted using a prospective, single-arm pre-/post-intervention design over 2 years. Fifty consecutive stage 3 and 4 CKD patients with resistant hypertension from the Regina Qu'Appelle Health Region (RQHR) multidisciplinary CKD clinic who agree to undergo RDN will be included in the study. Patients will be considered eligible if they are >18 years of age, exhibit a systolic BP of greater than 140 mm Hg despite maximal doses of 3 agents (1 of which is a diuretic) or are currently on 4 BP meds to control SBP to less than 140 mm Hg. Once identified as having resistant hypertension based on chart review, the patients will undergo the following assessments: 24-hour urine for catecholamines, sodium and cortisol; CT renal angiogram for the length and diameter of the renal arteries, to rule out stenosis/fibromuscular dysplasia, and assessment of the adrenal gland for nodules; and measurements of thyroid stimulating hormone (TSH) and serum cortisol to exclude secondary causes of hypertension. If no secondary causes of hypertension are identified, then the study coordinator will approach the patient at their next clinic appointment regarding participation in the trial

Patients will be excluded if the evaluations identify functional adrenal adenoma; a CT scan reveals a renal artery length (on either side) of less than 20 mm or diameter of less than 4 mm; they are pregnant or planning pregnancy within the study period; there is documented evidence of moderate-to-severe aortic stenosis; a cardiac event necessitating introduction of clopidogrel occurred during the prior 12 months; or they are currently using Warfarin or have a history of CVA within 6 months prior to the procedure. Patients on clonidine and other sympatholytic agents will not be excluded from the study. Our institutional review ethics board (REB-12-73) granted approval for the study. If a patient fit the criteria and agrees to undergo the procedure, the study coordinator will organize/perform the following assessments:

Ambulatory blood pressures and office blood pressures: Patients will undergo 24-hour blood pressure monitoring (Welch Allyn, Skaneateles Falls, NY, USA), and the following information will be documented: 12-hour daytime systolic pressure (mm Hg), 12-hour daytime diastolic pressure (mm Hg), 12-hour night-time systolic pressure (mm Hg) and 12-hour night-time diastolic pressure (mm Hg). The following day, the patient will have the 24-hour arm cuff removed, and they will sit in a quiet room for 10 minutes before the study coordinator can take further peripheral blood pressure measurements using BP Tru (BPM 100, BP Tru medical devices, Coquitlam, BC, Canada) on the non-dominant arm, which measures 6 consecutive blood pressures (the first is excluded, and the average of the last 5 readings will be documented).

Central blood pressure: After obtaining the mean of the 5 BP readings, radial artery waveforms will be recorded with a high-fidelity micromanometer from the wrist of the dominant arm and calibrated to the previously measured mean of 5 BP readings. Waveforms will be processed with dedicated software (Sphygmocor CPV (EM3) software version 9; AtCor Medical). The integral system software will be used to calculate an average radial artery waveform and to derive a corresponding central aortic pressure waveform using a previously validated generalized transfer function12,13. Aortic waveforms will be subject to further analysis using the SphygmoCor software to identify the time to the peak/shoulder of the first and second pressure wave components (T1, T2) during systole. The pressure at the peak/shoulder of the first component will be identified as the P1 height, and the pressure difference between this point and the maximal pressure during systole (Δ P, or augmentation) will be identified as the reflected wave during systole. The augmentation index (AIx), defined as the ratio of augmentation to the central pulse pressure, is expressed as a percentage: AIx: (Δ P/PP) X 100, where P is pressure, and PP is pulse pressure. Pulse pressure amplification (PPA) is expressed as the ratio of central pulse pressure (CPP) to brachial pulse pressure (PPP): PPA=PPP/CPP. At least 2 consecutive radial pressure wave samplings will be recorded for each patient, and the mean will be used for analysis. The collected data will include the augmentation index (%), augmentation pressure (mm Hg), central pulse pressure (mm Hg), central systolic pressure (mm Hg), central diastolic pressure (mm Hg), pulse pressure amplification (mm Hg), time to reflection (Tr) in ms and pulse wave velocity.