Letter to the EditorImprovement of renal function after renal sympathetic denervation vs.. deterioration of renal function in CKD patients with uncontrolled hypertension Twenty-four hour
Trang 1Letter 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
lower-ing effects in patients with CKD The improvement in eGFR
post-pro-cedure 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
hyper-tension may improve renal function The aim of this prospective
study was to compare the magnitude of the variations in renal
func-tion 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
pa-tients, 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
in-formed consent before inclusion This study was conducted in the
state of Rio de Janeiro, Brazil in the Hospital e Clínica São Gonçalo
Pa-tients were recruited from June 2013 to January 2015 and were derived
from the hospital and the public health network of the state county
Pa-tients who had the combination of the following criteria were
consecu-tively 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 eGFRN 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 be-tween two paired values were performed by the paired t-test in case
of Gaussian distribution or, alternatively, by the Wilcoxon test Compar-isons 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-valuesb0.05 were considered significant Correla-tions 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
IJC Metabolic & Endocrine 14 (2017) 38–39
Table 1 General features of patients at baseline.
Parameters CKD UHT CKD UHT RSD P-value
Age, years 59.0 ± 8.6 57.5 ± 10.2 0.3870 Body mass index, kg/m 2
29.0 ± 7.0 26.8 ± 5.4 0.0680
White ethnicity (%) 50 (69%) 30 (63%) 0.4374 Atrial fibrillation 30 (42%) 14 (29%) 0.1810 Hypertension 72 (100%) 48 (100%) 1.0000 Type 2 diabetes mellitus 31 (43%) 22 (46%) 0.8517 Hyperlipidemia 50 (69%) 30 (63%) 0.4374 Chronic kidney disease 72 (100%) 48 (100%) 1.0000
Creatinine, mg/dL 1.32 ± 1.09 1.42 ± 0.97 0.6081 eGFR, mL/min/1.73 m 2
62.0 ± 31.3 55.7 ± 33.0 0.2927 Albumin:creatinine ratio, mg/g 103.8 ± 15.6 97.5 ± 30.6 0.1406 Antihypertensive 4.36 ± 0.50 4.50 ± 0.36 0.0973 ACE-inhibitors/ARB 72 (100%) 48 (100%) 1.0000
DHP Ca ++
channel blockers 72 (100%) 48 (100%) 1.0000
Spironolactone 60 (83%) 39 (81%) 0.8093 Mean 24-hour ABPM, mm Hg
Systolic 156.4 ± 8.1 158.6 ± 9.6 0.1788 Diastolic 112.4 ± 7.8 110.6 ± 6.5 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 glo-merular 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/ ).
Contents lists available atScienceDirect
IJC Metabolic & Endocrine
j o u r n a l h o m e p a g e :h t t p : / / w w w j o u r n a l s e l s e v i e r c o m / i j c - m e t a b o l i c - a n d - e n d o c r i n e
Trang 2Table 1 During the 18 months of follow-up, the changes in mean
24-hour ABPM, serum creatinine, eGFR and ACR are displayed in
Table 2 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 m2and 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
(Pb 0.0001), as shown inTable 2 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
tech-nical support
References
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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
and the European Society of Cardiology 2013 ESH/ESC practice guidelines for the management of arterial hypertension, Eur Heart J 34 (2013) 2159–2219.
[2] G Grassi, Sympathetic neural activity in hypertension and related diseases, Am J Hypertens 23 (2010) 1052–1060.
[3] G Grassi, Assessment of sympathetic cardiovascular drive in human hypertension: achievements and perspectives, Hypertension 54 (2009) 690–697.
[4] J.F Paton, M.K Raizada, Neurogenic hypertension, Exp Physiol 95 (2010) 569–571.
[5] 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.
[6] 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.
[7] 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 com-plexes, J Interv Card Electrophysiol 30 (2016 May) (Epub ahead of print).
[8] 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 Clínica São Gonçalo, São Gonçalo, RJ, Brazil Corresponding author at: Rua Cel Moreira César, 138 - Centro, São
Gonçalo, Rio de Janeiro 24440–400, 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
Table 2
Parameters at baseline vs 18th month of follow-up.
Variable CKD UHT Baseline
(n = 72)
CKD UHT 18th month (n = 72)
P-value CKD UHT
CKD UHT RSD Baseline (n = 48)
CKD UHT RSD 18th month (n = 48)
P-value CKD UHT RSD
Mean 24-hour ABPM,
mm Hg
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⁎ b0.0001/b0.0001
Creatinine, mg/dL 1.32 ± 1.09 1.65 ± 0.86 0.0456 1.42 ± 0.97 0.86 ± 0.24 ⁎ 0.0002
eGFR, mL/min/1.73 m 2 62.0 ± 31.3 53.0 ± 20.5 0.0431 55.7 ± 33.0 94.3 ± 16.1 ⁎ 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 m 2
⁎ 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.
39 Letter to the Editor