Central Blood Pressure and Pulse Wave Velocity Changes Post Renal Denervation in Patients With Stages 3 and 4 Chronic Kidney Disease: The Regina RDN Study
Bhanu Prasad, Warren Berry, Kunal Goyal, Payam Dehghani, Raymond R Townsend, Bhanu Prasad, Warren Berry, Kunal Goyal, Payam Dehghani, Raymond R Townsend
Abstract
Background: Central aortic blood pressures and arterial stiffness are better indicators of cardiovascular outcomes than brachial blood pressures. However, their response to renal denervation (RDN) in patients with Stage 3 and Stage 4 chronic kidney disease (CKD) has not yet been examined.
Objective: To evaluate the impact of RDN on central blood pressures (CBP), brachial (office and ambulatory) blood pressures, arterial stiffness, glomerular filtration rate (GFR), 24-hour urine protein, and selective cardiac parameters observed on echocardiograms.
Design: Single-center, single-arm with pre-/post-RDN follow-up.
Setting: Patients were recruited from the multidisciplinary CKD clinic, Regina General Hospital, Canada.
Patients: About 25 consecutive patients with Stage 3 or Stage 4 CKD and resistant hypertension, with no radiological or laboratory evidence of secondary causes of hypertension.
Measurements: The key measurements were CBP, pulse wave velocity, ambulatory 24-hour blood pressure, office blood pressures on BP Tru, GFR, 24-hour urine protein and sodium, dose and number of blood pressure medication and doses.
Methods: The primary outcome measure was the change in CBP from baseline to 6 months post-RDN. Secondary outcome measures included changes in CBP, office blood pressure, 24-hour ambulatory pressures, pulse wave velocity, kidney function (eGFR and 24-hour protein excretion), and the change in the number and dose of medications during the 2-year follow-up period. The primary outcome and the secondary outcomes were evaluated using a Friedman's analysis of variance (ANOVA) and Wilcoxon signed-rank test for changes from post RDN procedure. Bonferroni correction was used to adjust P values for multiple testing. A two-sided alpha of .05 was used.
Results: Median central blood pressures (mm Hg) were 127/75 at baseline versus 118/70 at 6 months and 118/67 at 24 months (P = .13). Median office blood pressures (mm Hg) were 148/76 at baseline versus 135/75 at 6 months and 133/75 at 24 months (P ≤ .001). Median ambulatory 24-hour day (mm Hg) was 148/64 at baseline and 146/68 at 6 months and 152/67 at 24 months (P = .60). Median pulse wave velocity (m/s) at baseline was 13.8 at baseline versus 13.3 m/s at 6 months and 12.3 at 12 months' time (P = .62). Estimated glomerular filtration rate (mL/min/1.73m2) at baseline was 37, at 6 months was 36 and 34 at 24 months (P = .33).
Limitations: Single-center study, with no sham arm.
Conclusions: Our study demonstrates that there was a significant improvement in office blood pressures from baseline to 6 months, maintained to 24 months. There was a numerical improvement in central pressures, and pulse wave velocity at 6 and 24 months, with no sustained changes noted in 24-hour blood pressure. Kidney function remained at or near baseline throughout the 24 months of observation.
Trial registration: ClinicalTrials.gov (NCT01832233).
Keywords: central blood pressure; chronic kidney disease; chronic renal failure; renal denervation; resistant hypertension.
Conflict of interest statement
Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Raymond Townsend is a Consultant for Medtronic. No other authors have any conflict of interest.
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References
- Converse RL, Jr, Jacobsen TN, Toto RD, et al. Sympathetic overactivity in patients with chronic renal failure. N Engl J Med. 1992;327:1912-1918.
- Hausberg M, Kosch M, Harmelink P, et al. Sympathetic nerve activity in end-stage renal disease. Circulation. 2002;106:1974-1979.
- Sata Y, Schlaich MP. The potential role of catheter-based renal sympathetic denervation in chronic and end-stage kidney disease. J Cardiovasc Pharmacol Ther. 2016;21:344-352.
- Schlaich MP, Sobotka PA, Krum H, Whitbourn R, Walton A, Esler MD. Renal denervation as a therapeutic approach for hypertension: novel implications for an old concept. Hypertension. 2009;54:1195-1201.
- Laurent S, Boutouyrie P, Asmar R, et al. Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients. Hypertension. 2001;37:1236-1241.
- Weber T, Auer J, O’Rourke MF, et al. Arterial stiffness, wave reflections, and the risk of coronary artery disease. Circulation. 2004;109:184-189.
- Sutton-Tyrrell K, Najjar SS, Boudreau RM, et al. Elevated aortic pulse wave velocity, a marker of arterial stiffness, predicts cardiovascular events in well-functioning older adults. Circulation. 2005;111:3384-3390.
- Safar ME, Blacher J, Pannier B, et al. Central pulse pressure and mortality in end-stage renal disease. Hypertension. 2002;39:735-738.
- Brandt MC, Reda S, Mahfoud F, Lenski M, Bohm M, Hoppe UC. Effects of renal sympathetic denervation on arterial stiffness and central hemodynamics in patients with resistant hypertension. J Am Coll Cardiol. 2012;60:1956-1965.
- Laurent S, Schlaich M, Esler M. New drugs, procedures, and devices for hypertension. Lancet. 2012;380:591-600.
- Bakris G, Nathan S. Renal denervation and left ventricular mass regression: a benefit beyond blood pressure reduction? J Am Coll Cardiol. 2014;63:1924-1925.
- Townsend RR, Chirinos JA, Parsa A, et al. Central pulse pressure in chronic kidney disease: a chronic renal insufficiency cohort ancillary study. Hypertension. 2010;56:518-524.
- Townsend RR, Wimmer NJ, Chirinos JA, et al. Aortic PWV in chronic kidney disease: a CRIC ancillary study. Am J Hypertens. 2010;23:282-289.
- Krum H, Schlaich M, Whitbourn R, et al. Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study. Lancet. 2009;373:1275-1281.
- Symplicity HTN-2 Investigators, Esler MD, Krum H, et al. Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial. Lancet. 2010;376:1903-1909.
- Hackam DG, Quinn RR, Ravani P, et al. The 2013 Canadian Hypertension Education Program recommendations for blood pressure measurement, diagnosis, assessment of risk, prevention, and treatment of hypertension. Can J Cardiol. 2013;29:528-542.
- Pauca AL, O’Rourke MF, Kon ND. Prospective evaluation of a method for estimating ascending aortic pressure from the radial artery pressure waveform. Hypertension. 2001;38:932-937.
- Chen CH, Nevo E, Fetics B, et al. Estimation of central aortic pressure waveform by mathematical transformation of radial tonometry pressure. Validation of generalized transfer function. Circulation. 1997;95:1827-1836.
- Hering D, Mahfoud F, Walton AS, et al. Renal denervation in moderate to severe CKD. J Am Soc Nephrol. 2012;23:1250-1257.
- Ott C, Mahfoud F, Schmid A, et al. Renal denervation preserves renal function in patients with chronic kidney disease and resistant hypertension. J Hypertens. 2015;33:1261-1266.
- Kiuchi MG, Chen S, Andrea BR, et al. Renal sympathetic denervation in patients with hypertension and chronic kidney disease: does improvement in renal function follow blood pressure control? J Clin Hypertens (Greenwich). 2014;16:794-800.
- Azizi M, Sapoval M, Gosse P, et al. Optimum and stepped care standardised antihypertensive treatment with or without renal denervation for resistant hypertension (DENERHTN): a multicentre, open-label, randomised controlled trial. Lancet. 2015;385:1957-1965.
Source: PubMed