improvement of renal function after renal sympathetic denervation vs deterioration of renal function in ckd patients with uncontrolled hypertension

IJC Metabolic & Endocrine 14 (2017) 38–39 Contents lists available at ScienceDirect IJC Metabolic & Endocrine journal homepage: http://www.journals.elsevier.com/ijc-metabolic-and-endocrine Letter to the Editor Improvement of renal function after renal sympathetic denervation vs deterioration of renal function in CKD patients with uncontrolled hypertension Twenty-four hour ambulatory blood pressure measurements (ABPM) play an important role in hypertension management [1] Hypertension is defined as mean systolic BP levels ≥ 130 mm Hg and/ or diastolic BP ≥ 80 mm Hg in 24-hour ABPM [1] Sympathetic hyperactivity is well known to increase cardiovascular risk in chronic kidney disease (CKD) patients and is a hallmark of an essential hypertensive state that occurs early in the clinical course of the disease [2–4] The interruption of sympathetic hyperactivity and feedback of the renin–angiotensin–aldosterone system cycle can at least partly be beneficial for this population Recently, Hering and colleagues reported that renal sympathetic denervation (RSD) slows further progression of renal function irrespective of BP lowering effects in patients with CKD The improvement in eGFR post-procedure may be associated with alterations of intrarenal and glomerular haemodynamics achieved with RSD via inhibition of sympathetic outflow to the renal vasculature [5] Based on these pathophysiological mechanisms, RSD in CKD patients with hypertension may improve renal function The aim of this prospective study was to compare the magnitude of the variations in renal function in CKD patients with uncontrolled hypertension (UHT) who did not undergo RSD vs patients underwent RSD We conducted a prospective, longitudinal study of 120 CKD UHT patients, being 72 did not undergo RSD and 48 underwent RSD The study was conducted in accordance with the Helsinki Declaration and approved by the local ethics committee All patients gave written informed consent before inclusion This study was conducted in the state of Rio de Janeiro, Brazil in the Hospital e Clớnica Sóo Gonỗalo Patients were recruited from June 2013 to January 2015 and were derived from the hospital and the public health network of the state county Patients who had the combination of the following criteria were consecutively enrolled: (i) UHT: mean 24-hour ABPM ≥130/≥80 mm Hg despite treatment with non-pharmacological measures and use of at least three antihypertensive drugs (including a diuretic) on maximally tolerated doses or confirmed intolerance to medications; (ii) glomerular filtration rate estimated by the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation, eGFR [6], N60 mL/min/1.73 m2 between 15 and 89 mL/min/1.73 m2 (patients with eGFR N 60 mL/min/1.73 m2 were required to have microalbuminuria); (iv) age from 18 to 80 years.; and (v) able to read, understand and sign the informed consent form, and attend clinic visits and exams Patients with any of the following criteria were excluded: (i) pregnancy; (ii) valvular heart disease with significant adverse sequelae; (iii) myocardial infarction, unstable angina, stroke or transient ischemic attack within the previous six months; (iv) renovascular abnormalities; (v) psychiatric disease; (vi) allergy to ionic contrast; (vii) inability to be followed clinically after the procedure; and (viii) serious disease, which in the opinion of the investigator, may adversely affect the safety and/or efficacy of the participant or the study The 24-hour ABPM [7] and the renal sympathetic denervation are previously described [8] by our group The results were expressed as the mean and standard deviation (mean ± SD) of the mean in the case of normal distribution and as the median with inter-quartile range otherwise Statistical tests were all two-sided Comparisons between two paired values were performed by the paired t-test in case of Gaussian distribution or, alternatively, by the Wilcoxon test Comparisons between more than two paired values were performed by ANOVA for repeated measures or with Kruskal–Wallis ANOVA as appropriate complemented by a post hoc test Frequencies were compared with Fisher's Exact Test P-values b0.05 were considered significant Correlations between two variables were performed by Pearson in the case of Gaussian distribution or, alternatively, with the Spearman correlation test All statistical analysis was performed using the program GraphPad Prism v 7.0 (GraphPad Software, La Jolla, CA, USA) The general features of the 108 CKD hypertensive patients, divided into 72 did not undergo RSD, and 48 underwent RSD are listed in Table General features of patients at baseline Parameters CKD UHT CKD UHT RSD P-value N Age, years Body mass index, kg/m2 Male sex (%) White ethnicity (%) Atrial fibrillation Hypertension Type diabetes mellitus Hyperlipidemia Chronic kidney disease Stage Stage Stage Creatinine, mg/dL eGFR, mL/min/1.73 m2 Albumin:creatinine ratio, mg/g Antihypertensive ACE-inhibitors/ARB Diuretics DHP Ca++ channel blockers β-blockers α-Blockers Spironolactone 72 59.0 ± 8.6 29.0 ± 7.0 38 (53%) 50 (69%) 30 (42%) 72 (100%) 31 (43%) 50 (69%) 72 (100%) 38 (53%) 18 (25%) 16 (22%) 1.32 ± 1.09 62.0 ± 31.3 103.8 ± 15.6 4.36 ± 0.50 72 (100%) 72 (100%) 72 (100%) 43 (60%) 42 (58%) 60 (83%) 48 57.5 ± 10.2 26.8 ± 5.4 31 (65%) 30 (63%) 14 (29%) 48 (100%) 22 (46%) 30 (63%) 48 (100%) 20 (42%) 14 (29%) 14 (29%) 1.42 ± 0.97 55.7 ± 33.0 97.5 ± 30.6 4.50 ± 0.36 48 (100%) 48 (100%) 48 (100%) 31 (65%) 23 (48%) 39 (81%) – 0.3870 0.0680 0.2584 0.4374 0.1810 1.0000 0.8517 0.4374 1.0000 0.2662 0.6756 0.3988 0.6081 0.2927 0.1406 0.0973 1.0000 1.0000 1.0000 0.7021 0.2699 0.8093 Mean 24-hour ABPM, mm Hg Systolic Diastolic 156.4 ± 8.1 112.4 ± 7.8 158.6 ± 9.6 110.6 ± 6.5 0.1788 0.1889 Values are expressed as mean ± SD; ABPM, ambulatory blood pressure measurements; ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; CKD, chronic kidney disease; CHT, controlled hypertension; DHP, dihydropyridine; eGFR, estimated glomerular filtration rate; RSD, renal sympathetic denervation; UHT, uncontrolled hypertension http://dx.doi.org/10.1016/j.ijcme.2016.11.008 2214-7624/© 2016 The Authors Published by Elsevier Ireland Ltd This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) Letter to the Editor 39 Table Parameters at baseline vs 18th month of follow-up Variable CKD UHT Baseline (n = 72) Mean 24-hour ABPM, mm Hg Creatinine, mg/dL eGFR, mL/min/1.73 m2 ACR, mg/g Δ eGFR, mL/min/1.73 m2 156.4 ± 8.1/112.4 ± 7.8 155.3 ± 10.0/110.3 ± 9.4 0.4695/0.1468 158.6 ± 9.6/110.6 ± 6.5 134.3 ± 12.5⁎/86.3 ± 11.2⁎ 1.32 ± 1.09 62.0 ± 31.3 103.8 ± 15.6 – CKD UHT 18th month (n = 72) 1.65 ± 0.86 53.0 ± 20.5 98.5 ± 21.3 −9.0 ± 4.4 P-value CKD UHT 0.0456 0.0431 0.0907 – CKD UHT RSD Baseline (n = 48) 1.42 ± 0.97 55.7 ± 33.0 97.5 ± 30.6 – CKD UHT RSD 18th month (n = 48) 0.86 ± 0.24⁎ 94.3 ± 16.1⁎ 33.8 ± 21.0⁎ +38.6 ± 5.3⁎ P-value CKD UHT RSD b0.0001/b0.0001 0.0002 b0.0001 b0.0001 – Values are presented as mean ± SD; ABPM, ambulatory blood pressure measurements; ACR, albumin:creatinine ratio; CKD, chronic kidney disease; CHT, controlled hypertension; eGFR, estimated glomerular filtration rate; UHT, uncontrolled hypertension; variation (Δ) of eGFR, mL/min/1.73 m2 ⁎ P b 0.0001 for mean systolic and diastolic 24-hour ABPM, creatinine, eGFR, ACR, and Δ eGFR comparisons between both groups at 18th month of follow-up Table During the 18 months of follow-up, the changes in mean 24-hour ABPM, serum creatinine, eGFR and ACR are displayed in Table The variation (Δ) in the eGFR at the 18th month of follow-up after RSD showed a decrease of − 9.0 ± 4.4 mL/min/1.73 m2 and an increase of + 38.6 ± 5.3 mL/min/1.73 m2, in UHT CKD patients who did not undergo RSD and patients who underwent RSD, respectively (P b 0.0001), as shown in Table In this study, we reported that RSD is an effective tool to be used in CKD patients with UHT, corroborating the results presented by Hering and colleagues Funding This study was funded by Pacemed (US 400,000) Conflict of interest None declared Acknowledgements The authors thank all the participants in this study, especially, to Pacemed by stimulating the development of research and for the technical support References [1] G Mancia, R Fagard, K Narkiewicz, J Redon, A Zanchetti, M Böhm, T Christiaens, R Cifkova, G De Backer, A Dominiczak, M Galderisi, D.E Grobbee, T Jaarsma, P Kirchhof, S.E Kjeldsen, S Laurent, A.J Manolis, P.M Nilsson, L.M Ruilope, R.E Schmieder, P.A Sirnes, P Sleight, M Viigimaa, B Waeber, F Zannad, Task force for the management of arterial hypertension of the European Society of Hypertension [2] [3] [4] [5] [6] [7] [8] and the European Society of Cardiology 2013 ESH/ESC practice guidelines for the management of arterial hypertension, Eur Heart J 34 (2013) 2159–2219 G Grassi, Sympathetic neural activity in hypertension and related diseases, Am J Hypertens 23 (2010) 1052–1060 G Grassi, Assessment of sympathetic cardiovascular drive in human hypertension: achievements and perspectives, Hypertension 54 (2009) 690–697 J.F Paton, M.K Raizada, Neurogenic hypertension, Exp Physiol 95 (2010) 569–571 D Hering, P Marusic, J Duval, Y Sata, M Esler, A Walton, M Schlaich, Os 19-01 blood pressure independent effects of renal denervation on the decline of kidney function in patients with chronic kidney disease, J Hypertens 34 (Suppl 1) (2016 Sep) e228 A.S Levey, L.A Stevens, C.H Schmid, Y.L Zhang, A.F Castro III, H.I Feldman, J.W Kusek, P Eggers, F Van Lente, T Greene, J Coresh, CKD-EPI (chronic kidney disease epidemiology collaboration) A new equation to estimate glomerular filtration rate, Ann Intern Med 150 (2009) 604–612 M.G Kiuchi, E Silva GR, L.M Paz, S Chen, G.L Souto, Proof of concept study: renal sympathetic denervation for treatment of polymorphic premature ventricular complexes, J Interv Card Electrophysiol 30 (2016 May) (Epub ahead of print) M.G Kiuchi, D Mion Jr., M.L Graciano, M.A de Queiroz Carreira, T Kiuchi, S Chen, J.R Lugon, Proof of concept study: improvement of echocardiographic parameters after renal sympathetic denervation in CKD refractory hypertensive patients, Int J Cardiol 207 (2016) 6–12 Márcio Galindo Kiuchi⁎ Division of Cardiac Surgery and Artificial Cardiac Stimulation, Department of Medicine, Hospital e Clớnica Sóo Gonỗalo, Sóo Gonỗalo, RJ, Brazil Corresponding author at: Rua Cel Moreira César, 138 - Centro, Sóo Gonỗalo, Rio de Janeiro 24440400, Brazil E-mail address: marciokiuchi@gmail.com Shaojie Chen Department of Cardiology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China 19 October 2016 Available online xxxx ... Lugon, Proof of concept study: improvement of echocardiographic parameters after renal sympathetic denervation in CKD refractory hypertensive patients, Int J Cardiol 207 (2016) 6–12 Márcio Galindo... displayed in Table The variation (Δ) in the eGFR at the 18th month of follow-up after RSD showed a decrease of − 9.0 ± 4.4 mL/min/1.73 m2 and an increase of + 38.6 ± 5.3 mL/min/1.73 m2, in UHT CKD patients. .. Esler, A Walton, M Schlaich, Os 19-01 blood pressure independent effects of renal denervation on the decline of kidney function in patients with chronic kidney disease, J Hypertens 34 (Suppl 1)