The Impact on Central Blood Pressure and Arterial Stiffness Post Renal Denervation in Patients With Stage 3 and 4 Chronic Kidney Disease: The Prairie Renal Denervation Study

Bhanu Prasad, Jennifer Rose St Onge, Michelle C E McCarron, Kunal Goyal, Payam Dehghani, Bhanu Prasad, Jennifer Rose St Onge, Michelle C E McCarron, Kunal Goyal, Payam Dehghani

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, 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-RDN/post-RDN follow-up.

Setting: Patients are being recruited from the multidisciplinary CKD clinic.

Patients: Fifty 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 are central blood pressures, pulse wave velocity, ambulatory 24-hour blood pressure, office blood pressures on BP Tru, GFR, 24-hour urine protein and sodium, blood pressure medication, and doses.

Methods: For our primary outcome, we will compare changes in central blood pressures from baseline to 6 months post RDN using a paired t test or Mann-Whitney U test. Secondary outcomes will examine changes in central blood pressures from baseline to 3, 12, 18, and 24 months post RDN as well as changes in office pressures, GFR, 24-hour urine protein and sodium, and medications at all time points using mixed-model analyses of variance or Friedman test. Multiple regression may be used to control for potential covariates.

Limitations: Single-center study, with no sham arm.

Conclusions: Aortic blood pressure, rather than brachial blood pressure, optimally reflects the load placed on the left ventricle. Aortic blood pressure is also better associated with cardiovascular outcomes. If our study shows a preferential decrease in central blood pressures and improvements in cardiac parameters on echocardiograms post RDN, this may influence the way in which blood pressures are managed in clinics and offices.

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 no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Study flowchart. Note. CKD = chronic kidney disease; CT = computed tomography; TSH = thyroid stimulating hormone; ECHO = echocardiogram.

References

    1. De Caterina AR, Leone AM. Why beta-blockers should not be used as first choice in uncomplicated hypertension. Am J Cardiol. 2010;105(10):1433-1438.
    1. O’Rourke M. Mechanical principles in arterial disease. Hypertension. 1995;26(1):2-9.
    1. Mitchell GF, Lacourciere Y, Ouellet JP, et al. Determinants of elevated pulse pressure in middle-aged and older subjects with uncomplicated systolic hypertension: the role of proximal aortic diameter and the aortic pressure-flow relationship. Circulation. 2003;108(13):1592-1598.
    1. Izzo JL., Jr. Arterial stiffness and the systolic hypertension syndrome. Curr Opin Cardiol. 2004;19(4):341-352.
    1. Roman MJ, Devereux RB, Kizer JR, et al. Central pressure more strongly relates to vascular disease and outcome than does brachial pressure: the strong heart study. Hypertension. 2007;50(1):197-203.
    1. Safar ME, Blacher J, Pannier B, et al. Central pulse pressure and mortality in end-stage renal disease. Hypertension. 2002;39(3):735-738.
    1. Vlachopoulos C, Aznaouridis K, O’Rourke MF, Safar ME, Baou K, Stefanadis C. Prediction of cardiovascular events and all-cause mortality with central haemodynamics: a systematic review and meta-analysis. Eur Heart J. 2010;31(15):1865-1871.
    1. Williams B, Lacy PS, Thom SM, et al. Differential impact of blood pressure-lowering drugs on central aortic pressure and clinical outcomes: principal results of the Conduit Artery Function Evaluation (CAFE) study. Circulation. 2006;113(9):1213-1225.
    1. Townsend RR. Arterial stiffness and chronic kidney disease: lessons from the Chronic Renal Insufficiency Cohort study. Curr Opin Nephrol Hypertens. 2015;24(1):47-53.
    1. Guerin AP, Blacher J, Pannier B, Marchais SJ, Safar ME, London GM. Impact of aortic stiffness attenuation on survival of patients in end-stage renal failure. Circulation. 2001;103(7):987-992.
    1. Blacher J, Guerin AP, Pannier B, Marchais SJ, Safar ME, London GM. Impact of aortic stiffness on survival in end-stage renal disease. Circulation. 1999;99(18):2434-2439.
    1. London GM, Blacher J, Pannier B, Guerin AP, Marchais SJ, Safar ME. Arterial wave reflections and survival in end-stage renal failure. Hypertension. 2001;38(3):434-438.
    1. Schlaich MP, Lambert E, Kaye DM, et al. Sympathetic augmentation in hypertension: role of nerve firing, norepinephrine reuptake, and angiotensin neuromodulation. Hypertension. 2004;43(2):169-175.
    1. Grassi G, Seravalle G, Colombo M, et al. Body weight reduction, sympathetic nerve traffic, and arterial baroreflex in obese normotensive humans. Circulation. 1998;97(20):2037-2042.
    1. Narkiewicz K. Obesity and hypertension—the issue is more complex than we thought. Nephrol Dial Transplant. 2006;21(2):264-267.
    1. Converse RL, Jr, Jacobsen TN, Toto RD, et al. Sympathetic overactivity in patients with chronic renal failure. N Engl J Med. 1992;327(27):1912-1918.
    1. Hausberg M, Kosch M, Harmelink P, et al. Sympathetic nerve activity in end-stage renal disease. Circulation. 2002;106(15):1974-1979.
    1. Schlaich MP, Socratous F, Hennebry S, et al. Sympathetic activation in chronic renal failure. J Am Soc Nephrol. 2009;20(5):933-939.
    1. Laurent S, Schlaich M, Esler M. New drugs, procedures, and devices for hypertension. Lancet. 2012;380(9841):591-600.
    1. Bakris G, Nathan S. Renal denervation and left ventricular mass regression: a benefit beyond blood pressure reduction? J Am Coll Cardiol. 2014;63(18):1924-1925.
    1. Hering D, Mahfoud F, Walton AS, et al. Renal denervation in moderate to severe CKD. J Am Soc Nephrol. 2012;23(7):1250-1257.
    1. 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(6):1261-1266.
    1. 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(4):932-937.
    1. 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(7):1827-1836.
    1. 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(4):344-352.
    1. Peet MM. Hypertension and its surgical treatment by bilateral supradiaphragmatic splanchnicectomy. Am J Surg. 1948;75(1):48-68.
    1. 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(9671):1275-1281.
    1. Esler MD, Krum H, Sobotka PA, et al. ; for Symplicity HTN-2 investigators. Renal sympathetic denervation in patients with treatment-resistant hypertension (the Symplicity HTN-2 trial): a randomised controlled trial. Lancet. 2010;376:1903-1909.
    1. Bhatt DL, Kandzari DE, O’Neill WW, et al. A controlled trial of renal denervation for resistant hypertension. N Engl J Med. 2014;370(15):1393-1401.
    1. Fadl Elmula FE, Hoffmann P, Larstorp AC, et al. Adjusted drug treatment is superior to renal sympathetic denervation in patients with true treatment-resistant hypertension. Hypertension. 2014;63(5):991-999.
    1. Hering D, Mahfoud F, Walton AS, et al. Renal denervation in moderate to severe CKD. J Am Soc Nephrol. 2012;23(7):1250-1257.
    1. Holland DJ, Sacre JW, McFarlane SJ, Coombes JS, Sharman JE. Pulse wave analysis is a reproducible technique for measuring central blood pressure during hemodynamic perturbations induced by exercise. Am J Hypertens. 2008;21(10):1100-1106.
    1. Laurent S, Cockcroft J, Van Bortel L, et al. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J. 2006;27(21):2588-2605.
    1. Climie RE, Schultz MG, Nikolic SB, Ahuja KD, Fell JW, Sharman JE. Validity and reliability of central blood pressure estimated by upper arm oscillometric cuff pressure. Am J Hypertens. 2012;25(4):414-420.
    1. Roman MJ, Devereux RB, Kizer JR, et al. Central pressure more strongly relates to vascular disease and outcome than does brachial pressure: the strong heart study. Hypertension. 2007;50(1):197-203.
    1. Wang KL, Cheng HM, Chuang SY, et al. Central or peripheral systolic or pulse pressure: which best relates to target organs and future mortality? J Hypertens. 2009;27(3):461-467.
    1. Jankowski P, Kawecka-Jaszcz K, Czarnecka D, et al. Pulsatile but not steady component of blood pressure predicts cardiovascular events in coronary patients. Hypertension. 2008;51(4):848-855.
    1. Redfield MM, Jacobsen SJ, Burnett JC, Jr, Mahoney DW, Bailey KR, Rodeheffer RJ. Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic. JAMA. 2003;289(2):194-202.
    1. Bombelli M, Facchetti R, Carugo S, et al. Left ventricular hypertrophy increases cardiovascular risk independently of in-office and out-of-office blood pressure values. J Hypertens. 2009;27(12):2458-2464.
    1. Dhingra R, Gaziano JM, Djousse L. Chronic kidney disease and the risk of heart failure in men. Circ Heart Fail. 2011;4(2):138-144.
    1. Taddei S, Nami R, Bruno RM, Quatrini I, Nuti R. Hypertension, left ventricular hypertrophy and chronic kidney disease. Heart Fail Rev. 2011;16(6):615-620.
    1. Okin PM, Devereux RB, Jern S, et al. Regression of electrocardiographic left ventricular hypertrophy during antihypertensive treatment and the prediction of major cardiovascular events. JAMA. 2004;292(19):2343-2349.

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