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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Flowchart of patient selection&#46; Of the total number of patients observed in an outpatient hypertension clinic &#40;n&#61;318&#41;&#44; 253 were excluded for various reasons &#40;see main text&#41; and 65 underwent renal denervation&#46; Of these 65&#44; complete 12-month follow-up with ambulatory blood pressure monitoring and transthoracic echocardiographic data were available in 31 patients&#46; ABPM&#58; 24-h ambulatory blood pressure monitoring&#59; ACR&#58; albumin-to-creatinine ratio&#59; BP&#58; blood pressure&#59; eGFR&#58; estimated glomerular filtration rate&#59; RDN&#58; renal denervation&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Cardiovascular disease is the leading cause of morbidity and mortality in developed countries and hypertension is one of its most important risk factors&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">1</span></a> Some hypertensive patients have drug-resistant hypertension and are at a higher risk of events&#46;<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">2&#44;3</span></a> Besides clinical events&#44; assessment of target organ damage can provide earlier insights into the biological impact of hypertension&#46; For several years&#44; albuminuria has been recognized as an indicator of cardiovascular risk&#44; although the pathophysiology behind this association is still not fully understood&#46;<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">4&#8211;6</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">In recent years sympathetic renal denervation &#40;RDN&#41; has been developed as a treatment for the management of patients with resistant hypertension<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">7&#44;8</span></a> and it may have a positive impact on hypertension-related target organ damage&#46; An example is recently published reports of reductions in left ventricular hypertrophy after RDN&#46;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">9&#8211;11</span></a> The kidney is also an important organ in this context&#44; but evidence on the effect of RDN on proteinuria is still limited and results are conflicting&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">12&#44;13</span></a> The aim of the present study was to assess the impact of RDN on the albumin-to-creatinine ratio &#40;ACR&#41; at 12-month follow-up&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Study design and patient population</span><p id="par0015" class="elsevierStylePara elsevierViewall">From a single-center prospective registry including 318 patients with resistant hypertension referred for RDN between July 2011 and April 2015&#44; we included for the purpose of the present study 31 patients with complete information on blood pressure &#40;BP&#41; measurements &#40;both office and 24-h ambulatory blood pressure monitoring &#91;ABPM&#93;&#41; at baseline and 12 months&#44; transthoracic echocardiogram and renal function &#40;creatinine clearance and ACR&#41;&#44; out of 65 patients who were considered good candidates and underwent RDN &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">The details of this patient population have been previously described&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">11&#44;14</span></a> Briefly&#44; all patients who underwent RDN were aged over 18 years&#44; with persistent office systolic blood pressure &#40;SBP&#41; above 160 mmHg even after optimal antihypertensive therapy &#40;at least three drugs&#44; including a diuretic&#41;&#46; Before RDN all patients were studied for secondary causes of hypertension and visited regularly &#40;for at least six weeks&#41; in order to ensure drug regime optimization and full compliance with medical treatment&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Demographic&#44; clinical&#44; anthropometric&#44; laboratory and procedural data were recorded and stored in a dedicated database and written informed consent was obtained from all patients&#46; The study was approved by the ethics committee of Hospital de Santa Cruz and Nova Medical School&#44; Lisbon&#44; Portugal&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Blood pressure measurement and definition of responders</span><p id="par0030" class="elsevierStylePara elsevierViewall">Office BP readings were measured in a seated position&#44; after a 5 min rest &#40;in accordance with the European guidelines for the management of arterial hypertension&#41;&#44; using an Omron HEM-907 semiautomatic oscillometric sphygmomanometer &#40;Omron Healthcare&#44; USA&#41;&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">At baseline&#44; before RDN&#44; BP measurements were taken in both arms and the arm with the higher BP was selected for all subsequent readings&#46; The mean of three measurements was used for analysis&#46; An ABM monitor &#40;Spacelabs Healthcare&#44; USA&#41; was used for 24-h ABPM assessment&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Patients with a decrease of 10 mmHg or more in office SBP or of 2 mmHg or more in 24-h ABPM SBP at 12-month follow-up were considered to be BP responders to RDN&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">11&#44;15</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Renal function and albuminuria measurement</span><p id="par0045" class="elsevierStylePara elsevierViewall">Creatinine clearance was estimated using the Chronic Kidney Disease Epidemiology Collaboration &#40;CKD-EPI&#41; formula&#46; Albuminuria was obtained in spot urine and measured using the ACR&#44; expressed in mg&#47;g&#44; which is equivalent to 24-h albumin excretion in mg&#47;day&#46; ACR values were acquired before RDN &#40;at baseline&#41; and at 12-month follow-up&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Renal denervation procedure</span><p id="par0050" class="elsevierStylePara elsevierViewall">RDN procedures were performed using mild anesthesia &#40;propofol and remifentanil&#41; for sedation and pain control&#46; An activated clotting time of 250-300 s was obtained with unfractionated heparin&#46; After femoral artery access&#44; abdominal aortography and selective renal artery angiography were performed to confirm anatomic eligibility&#46; In all cases&#44; the femoral access site was closed using a sealing device &#40;Angio-Seal<span class="elsevierStyleSup">&#174;</span>&#44; St&#46; Jude Medical&#44; USA&#41;&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Denervation was performed using the following radiofrequency systems&#58; Symplicity<span class="elsevierStyleSup">&#174;</span> &#40;n&#61;25&#41;&#44; EnligHTN<span class="elsevierStyleSup">&#174;</span> &#40;n&#61;4&#41; and OneShot<span class="elsevierStyleSup">&#174;</span> &#40;n&#61;2&#41;&#44; in accordance with standard techniques&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Statistical analysis</span><p id="par0060" class="elsevierStylePara elsevierViewall">Continuous variables are reported as mean &#177; standard deviation&#46; Normality was tested with the Kolmogorov-Smirnov test and&#47;or visual assessment of a Q-Q plot&#46; Normally distributed variables were compared between baseline and 12-month follow-up using a paired Student&#39;s t test&#44; or a Wilcoxon matched-pairs test if not normally distributed&#46; Discrete variables are expressed as frequencies and percentages&#46; Statistical comparisons of characteristics at baseline and at follow-up were performed using the chi-square test or Fisher&#39;s exact test&#44; as appropriate&#44; for categorical variables and the paired Student&#39;s t test for continuous variables&#46; A two-tailed p value &#60;0&#46;05 was considered as statistically significant&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">SPSS<span class="elsevierStyleSup">&#174;</span> version 21&#46;0 &#40;IBM SPSS Inc&#44; Chicago&#44; IL&#41; was used for data processing and statistical analysis&#46;</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Results</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Patient characteristics</span><p id="par0070" class="elsevierStylePara elsevierViewall">A total of 318 patients were observed in an outpatient hypertension clinic between 2011 and 2015&#46; Of these&#44; 253 were excluded due to&#58; &#40;a&#41; BP control being achieved after dose and&#47;or drug changes &#40;n&#61;139&#41;&#59; &#40;b&#41; a secondary cause of hypertension &#40;n&#61;31&#41;&#59; &#40;c&#41; renal anatomy considered unsuitable for RDN on computed tomography angiography&#59; &#40;d&#41; estimated glomerular filtration rate &#40;eGFR&#41; &#60;30 ml&#47;min&#47;1&#46;73 m<span class="elsevierStyleSup">2</span>&#59; &#40;e&#41; patient refusal after discussion of the expected benefits and risks&#46; A total of 65 patients were considered good candidates and underwent RDN&#46; Of these&#44; the first 31 with complete data on blood and urine samples&#44; office BP and 24-h ABPM&#44; and transthoracic echocardiogram at both baseline and 12-month follow-up were included in the present analysis &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>&#41;&#46; Data on left ventricular mass and function have been reported elsewhere&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">11</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Mean age was 65&#177;7 years&#44; all patients were Caucasian and 48&#37; &#40;n&#61;14&#41; were male&#46; Regarding cardiovascular risk factors&#44; 71&#37; had type 2 diabetes&#44; 68&#37; were obese &#40;mean body mass index 32&#177;6 kg&#47;m<span class="elsevierStyleSup">2</span>&#41;&#44; 68&#37; had dyslipidemia and only one patient was an active smoker&#46; Ten patients &#40;33&#37;&#41; had manifestations of vascular disease &#40;mainly coronary artery disease&#41;&#46; Mean eGFR was 76&#46;4&#177;24&#46;7 ml&#47;min&#47;1&#46;73 m<span class="elsevierStyleSup">2</span> and five patients had chronic kidney disease &#40;eGFR &#60;60 ml&#47;min&#47;1&#46;73 m<span class="elsevierStyleSup">2</span>&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; At baseline&#44; median ACR was 25&#46;8 &#40;interquartile range &#91;IQR&#93; 9&#46;0-574&#46;0&#41; and 15 &#40;48&#37;&#41; patients had ACR &#62;30 mg&#47;g&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">Most patients &#40;90&#37;&#41; had known hypertension for at least 10 years and were treated at baseline with a mean of 5&#46;8 anti-hypertensive drugs&#44; corresponding to a mean of 5&#46;5 different drug classes&#46; Of note&#44; 74&#37; were treated with spironolactone&#46; Details on antihypertensive medication at baseline and follow-up are presented in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Blood pressure control</span><p id="par0085" class="elsevierStylePara elsevierViewall">Mean office SBP and diastolic BP &#40;DBP&#41; at baseline were 176&#177;24 mmHg and 90&#177;14 mmHg&#44; respectively&#44; and mean heart rate was 73&#177;11 bpm&#46; On 24-h ABPM&#44; mean SBP and DBP were 150&#177;20 mmHg and 83&#177;10 mmHg&#44; respectively &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">At 12-month follow-up mean SBP had decreased from 176&#177;24 to 149&#177;13 mmHg &#40;p&#60;0&#46;001&#41; and DBP from 90&#177;14 to 79&#177;11 mmHg &#40;p&#60;0&#46;001&#41;&#46; These changes were consistent with the results of 24-h ABPM&#44; in which mean SBP decreased from 150&#177;20 to 132&#177;14 mmHg &#40;p&#60;0&#46;001&#41; and mean DBP from 83&#177;10 to 74&#177;9 mmHg &#40;p&#61;0&#46;001&#41;&#46; At 12-month follow-up&#44; 71&#37; of patients were considered office SBP responders and 84&#37; were considered ABPM SBP responders &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; During this period there was also a reduction in the number of antihypertensive drugs and classes taken&#59; the number of drugs decreased from 5&#46;8&#177;1&#46;1 to 5&#46;0&#177;1&#46;2 &#40;p&#61;0&#46;002&#41; and drug classes from 5&#46;5&#177;0&#46;9 to 4&#46;9&#177;1&#46;1 &#40;p&#61;0&#46;02&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Changes in albumin-to-creatinine ratio after renal denervation and relation with blood pressure control</span><p id="par0095" class="elsevierStylePara elsevierViewall">At baseline&#44; median ACR was 25&#46;8 mg&#47;g &#40;IQR 9&#46;0-574&#46;0 mg&#47;g&#41; and 48&#46;4&#37; of patients &#40;n&#61;15&#41; had an ACR &#62;30 mg&#47;g&#46; We found a significant reduction at 12-month follow-up to a median of 14&#46;8 mg&#47;g &#40;IQR 4&#46;5-61&#46;0 mg&#47;g&#44; p&#61;0&#46;007&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Interestingly&#44; we also found a significant reduction in the percentage of patients with ACR &#62;30 mg&#47;g between baseline and 12-month follow-up &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a>&#41;&#46; Considering patients with any ACR reduction as ACR responders&#44; 77&#46;4&#37; &#40;n&#61;24&#41; of patients were ACR responders&#46; The distribution of patients across the different classes of urinary albumin excretion also demonstrated a favorable effect &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Figure 3</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0105" class="elsevierStylePara elsevierViewall">When the results were split according to ABPM SBP responder status&#44; we found a significant reduction in responders &#40;from 25&#46;6 mg&#47;g &#91;IQR 8&#46;7-382&#46;8 mg&#47;g&#93; to 15&#46;9 mg&#47;g &#91;IQR 4&#46;4-55&#46;0 mg&#47;g&#93;&#44; p&#61;0&#46;009&#41;&#44; and a numerical decrease in non-responders &#40;from 165&#46;0 mg&#47;g &#91;IQR 8&#46;8-1423&#46;5 mg&#47;g&#93; to 13&#46;6 mg&#47;dl &#91;IQR 5&#46;7-1417&#46;0 mg&#47;g&#93;&#44; p&#61;0&#46;345&#41;&#44; probably due to the small number of patients in this subgroup &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> and <a class="elsevierStyleCrossRef" href="#fig0020">Figure 4</a>&#41;&#46; The same analysis was performed according to dipper status and the results were similar&#44; with a significant reduction in patients with dipper status on baseline ABPM &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> and <a class="elsevierStyleCrossRef" href="#fig0025">Figure 5</a>&#41;&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><elsevierMultimedia ident="fig0025"></elsevierMultimedia><p id="par0110" class="elsevierStylePara elsevierViewall">With regard to diabetic status&#44; patients with diabetes had a higher median baseline ACR and showed a statistically significant decrease &#40;from 48&#46;9 mg&#47;g &#91;IQR 9&#46;1-1116&#46;3 mg&#47;g&#93; to 23&#46;1 mg&#47;g &#91;IQR 4&#46;3-123&#46;8 mg&#47;g&#93;&#44; p&#61;0&#46;028&#41;&#59; there was also a numerical decrease in ACR in non-diabetic patients &#40;from 25&#46;4 mg&#47;g &#40;IQR 5&#46;3-68&#46;6 mg&#47;g&#41; to 10&#46;9 mg&#47;dl &#40;IQR 3&#46;4-20&#46;8 mg&#47;g&#41;&#44; p&#61;0&#46;066&#41;&#44; probably also due to the small patient sample in this subgroup &#40;n&#61;9&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> and <a class="elsevierStyleCrossRef" href="#fig0030">Figure 6</a>&#41;&#46;</p><elsevierMultimedia ident="fig0030"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Safety</span><p id="par0115" class="elsevierStylePara elsevierViewall">There were four vascular access complications&#58; three hematomas and one femoral pseudoaneurysm&#46; No significant changes in eGFR were seen &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> and <a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a>&#41;&#46;</p></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Discussion</span><p id="par0120" class="elsevierStylePara elsevierViewall">The main findings of our study are&#58; &#40;1&#41; RDN was associated with a significant BP reduction at 12-month follow-up&#59; &#40;2&#41; there was a significant decrease in median ACR&#44; without significant changes in eGFR&#44; and a significant reduction in the percentage of patients with ACR &#62;30 mg&#47;g between baseline and 12-month follow-up&#59; &#40;3&#41; the reduction in ACR was observed in both BP responders and non-responders&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Although the initial results with catheter-based RDN were very promising&#44;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">7&#44;8&#44;16</span></a> the most recent and largest randomized trial&#44; SYMPLICITY HTN-3&#44;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">15</span></a> failed to meet its primary efficacy endpoint&#44; raising doubts about the real biological effect of this treatment&#46; The unexpected negative results of HTN-3 have been extensively discussed and many possible reasons have been put forward&#44; both clinical &#40;mainly related to patient selection&#41; and technical &#40;procedure-related&#44; particularly the number and pattern of radiofrequency applications&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">17</span></a> Another possible factor is how the efficacy of RDN is currently measured&#44; and examining target organ damage may provide a better assessment than BP values&#46; In line with this are the recent results in LV mass and function after RDN&#44; for which several groups have published positive results at six-month follow-up based on both transthoracic echocardiography<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">11&#44;18</span></a> and cardiac magnetic resonance imaging &#40;MRI&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">10</span></a> Our group recently reported a significant reduction in left ventricular mass at 12-month follow-up&#44; without correlation with changes in systolic ABPM&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">11</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">Another approach to monitoring hypertension-related target organ damage is to calculate ACR&#44; a recognized marker which has been linked to cardiovascular outcomes in several studies on hypertension&#46;<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">4&#8211;6</span></a> Ott et al&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">19</span></a> found a significant reduction in ACR at six-month follow-up in 59 patients with resistant hypertension &#40;mean 24-h ABPM SBP 156 mmHg&#44; treated with a mean of 5&#46;5 antihypertensive drugs&#41;&#46; In contrast with the latter study&#44; we also included patients with normal &#40;&#60;30 mg&#47;g&#41; baseline ACR and therefore our median values are lower that those reported by Ott et al&#46; Of note&#44; even among this mixed population of different ACR baseline profiles&#44; half of whom had normal urinary albumin excretion &#40;51&#46;6&#37; with ACR &#60;30 mg&#47;dl&#41;&#44; the mean age &#40;65 years&#41;&#44; baseline ABPM SBP &#40;150 mmHg&#41; and mean number of drugs &#40;5&#46;8&#41; were very similar to the study by Ott et al&#46; Our study also included a higher percentage of patients with type 2 diabetes &#40;71&#37;&#44; compared to 51&#37; in Ott et al&#46;&#8217;s study&#41;&#46; In another recently published single-center study&#44; Verloop et al&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">13</span></a> failed to demonstrate any significant decrease in either LV mass &#40;by cardiac MRI&#41; or urinary albumin excretion&#44; and found only a modest impact on blood pressure&#46; These results are in contrast with previous studies and our results&#44; and may have been due to differences in patient populations&#46; In the study by Verloop et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">13</span></a> the mean age was lower &#40;58 years&#41; and so was the mean number of drugs &#40;4&#44; as opposed to 5&#46;5 in Ott et al&#46; and 5&#46;8 in our study&#41;&#46; Other important differences are the much lower prevalence of diabetes &#40;only 15&#37;&#41; and the fact that the authors did not exclude patients with eGFR &#60;45 ml&#47;min&#47;1&#46;73 m<span class="elsevierStyleSup">2</span>&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">One interesting observation in our study is the fact that the reduction in ACR was also found in BP non-responders&#44; although this did not reach statistical significance&#44; probably due to the small size of this patient subgroup&#46; This raises the question of whether RDN&#44; by reducing sympathetic hyperactivity&#44; might have a positive direct effect on glomerular endothelial function independent of the hemodynamic effect derived from blood pressure reduction&#44; since there is a close association between urinary albumin excretion and glomerular endothelium dysfunction and glycocalyx loss&#46;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">5&#44;20</span></a> These two factors may be modulated by autonomic nervous system tone and&#44; in theory&#44; this positive impact on endothelial physiology could be linked to the expected decrease in overall cardiovascular risk that is the ultimate goal of RDN&#46; On the other hand&#44; endothelial dysfunction is only one of several effects of increased sympathetic activity&#44; a common denominator in cardiovascular and renal pathophysiology&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">21</span></a> Finally&#44; the ACR reduction seen in our study should be interpreted in the context of the high cardiovascular risk of patients with resistant hypertension&#44;<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">2&#44;3</span></a> and this reduction is expected to help to lower this risk&#44; although no prospective studies have been published on the prognostic impact of RDN on clinical outcomes&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Limitations</span><p id="par0140" class="elsevierStylePara elsevierViewall">The present study has some limitations that should be mentioned&#58; &#40;1&#41; it is a single-center prospective registry with a small sample size&#59; &#40;2&#41; the physicians following patients after RDN were not blinded&#44; although the most important outcome measurements &#40;24-h ABPM and ACR&#41; were performed by cardiac and laboratory technicians unaware of treatment status&#59; &#40;3&#41; there was no control group or sham procedure&#59; &#40;4&#41; changes were made in antihypertensive therapy during follow-up&#44; which could have influenced reductions in blood pressure and ACR &#40;but the mean number of drugs actually decreased during follow-up&#44; which could lead to underestimation of the benefit of RDN in this daily practice setting&#41;&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Conclusions</span><p id="par0145" class="elsevierStylePara elsevierViewall">In this single-center unblinded study of patients with resistant hypertension undergoing RDN&#44; we found a significant reduction in both office BP and 24-h ABPM which was associated with a significant decrease in median ACR&#44; without significant changes in eGFR&#46; At 12-month follow-up&#44; there was a reduction in the percentage of patients with pathological urinary albumin excretion&#44; and this reduction was independent of BP responder status&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Ethical disclosures</span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Protection of human and animal subjects</span><p id="par0150" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this study&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Confidentiality of data</span><p id="par0155" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article&#46;</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Right to privacy and informed consent</span><p id="par0160" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article&#46;</p></span></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Conflicts of interest</span><p id="par0165" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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              "titulo" => "Conclus&#227;o"
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          "titulo" => "Palavras-chave"
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          "titulo" => "Introduction"
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        5 => array:3 [
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          "titulo" => "Methods"
          "secciones" => array:5 [
            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Study design and patient population"
            ]
            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Blood pressure measurement and definition of responders"
            ]
            2 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Renal function and albuminuria measurement"
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            3 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Renal denervation procedure"
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              "titulo" => "Statistical analysis"
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          "titulo" => "Results"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "sec0045"
              "titulo" => "Patient characteristics"
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            1 => array:2 [
              "identificador" => "sec0050"
              "titulo" => "Blood pressure control"
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            2 => array:2 [
              "identificador" => "sec0055"
              "titulo" => "Changes in albumin-to-creatinine ratio after renal denervation and relation with blood pressure control"
            ]
            3 => array:2 [
              "identificador" => "sec0060"
              "titulo" => "Safety"
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          ]
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          "titulo" => "Discussion"
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          "identificador" => "sec0070"
          "titulo" => "Limitations"
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          "titulo" => "Conclusions"
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          "titulo" => "Ethical disclosures"
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            0 => array:2 [
              "identificador" => "sec0085"
              "titulo" => "Protection of human and animal subjects"
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            1 => array:2 [
              "identificador" => "sec0090"
              "titulo" => "Confidentiality of data"
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              "identificador" => "sec0095"
              "titulo" => "Right to privacy and informed consent"
            ]
          ]
        ]
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          "identificador" => "sec0100"
          "titulo" => "Conflicts of interest"
        ]
        12 => array:1 [
          "titulo" => "References"
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    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2016-07-22"
    "fechaAceptado" => "2016-09-26"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec839110"
          "palabras" => array:4 [
            0 => "Resistant hypertension"
            1 => "Renal denervation"
            2 => "Albuminuria"
            3 => "Blood pressure"
          ]
        ]
      ]
      "pt" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palavras-chave"
          "identificador" => "xpalclavsec839111"
          "palabras" => array:4 [
            0 => "Hipertens&#227;o arterial resistente"
            1 => "Desnerva&#231;&#227;o renal"
            2 => "Albumin&#250;ria"
            3 => "Press&#227;o arterial"
          ]
        ]
      ]
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    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Sympathetic renal denervation &#40;RDN&#41; was developed as a treatment for the management of patients with resistant hypertension&#46; This procedure may have a positive impact on hypertension-related target organ damage&#44; particularly renal disease&#44; but the evidence is still limited&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objective</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">To assess the impact of RDN on the albumin-to-creatinine ratio &#40;ACR&#41; at 12-month follow-up&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Methods and Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">From a single-center prospective registry including 65 patients with resistant hypertension undergoing renal denervation&#44; 31 patients with complete baseline and 12-month follow-up blood pressure &#40;BP&#41; measurements &#40;both office and 24-h ambulatory blood pressure monitoring &#91;ABPM&#93;&#41; and ACR were included in the present study&#46; Mean age was 65&#177;7 years&#44; 52&#37; were female&#44; most &#40;90&#37;&#41; had been diagnosed with hypertension for more than 10 years&#44; 71&#37; had type 2 diabetes and 33&#37; had vascular disease in at least one territory&#46; Mean estimated glomerular filtration rate was 73&#46;6&#177;25&#46;1 ml&#47;min&#47;1&#46;73 m<span class="elsevierStyleSup">2</span> and 15 patients &#40;48&#37;&#41; had an ACR &#62;30 mg&#47;g&#46; After 12 months&#44; 22 patients were considered BP responders &#40;73&#37;&#41;&#46; ACR decreased significantly from a median of 25&#46;8 mg&#47;g &#40;interquartile range &#91;IQR&#93; 9&#46;0-574&#46;0 mg&#47;g&#41; to 14&#46;8 mg&#47;g &#40;IQR 4&#46;5-61&#46;0 mg&#47;g&#44; p&#61;0&#46;007&#41;&#46; When the results were split according to systolic BP responder status on ABPM&#44; we found a significant reduction in responders &#40;from 25&#46;6 mg&#47;g &#91;IQR 8&#46;7-382&#46;8 mg&#47;g&#93; to 15&#46;9 mg&#47;g &#91;IQR 4&#46;4-55&#46;0 mg&#47;g&#93;&#44; p&#61;0&#46;009&#41;&#44; and a numerical decrease in the non-responder subgroup &#40;from 165&#46;0 mg&#47;g &#91;IQR 8&#46;8-1423&#46;5 mg&#47;g&#93; to 13&#46;6 mg&#47;dl &#91;IQR 5&#46;7-1417&#46;0 mg&#47;g&#93;&#44; p&#61;0&#46;345&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Besides significant reductions in blood pressure &#40;both office and 24-h ABPM&#41;&#44; renal denervation was associated with a significant reduction in ACR&#44; a recognized marker of target organ damage&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Introduction"
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          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Objective"
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          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Methods and Results"
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            "identificador" => "abst0020"
            "titulo" => "Conclusions"
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      ]
      "pt" => array:3 [
        "titulo" => "Resumo"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introdu&#231;&#227;o</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">A desnerva&#231;&#227;o simp&#225;tica renal &#40;RDN&#41; foi desenvolvida como uma forma de tratamento para os doentes com hipertens&#227;o arterial resistente &#40;R-HTN&#41;&#46; Este procedimento poder&#225; ter um impacto favor&#225;vel nas les&#245;es de &#243;rg&#227;o alvo relacionadas com a hipertens&#227;o&#44; nomeadamente a doen&#231;a renal&#44; no entanto&#44; a evid&#234;ncia dispon&#237;vel ainda &#233; escassa&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Objetivo</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Avaliar o impacto da RDN no r&#225;cio albumina-creatinina &#40;ACR&#41; aos 12 meses de seguimento ap&#243;s RDN&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">M&#233;todos e resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Registo prospetivo de centro &#250;nico incluindo 65 doentes com R-HTN submetidos a RDN&#44; dos quais 31 doentes com avalia&#231;&#227;o basal e a um ano completa da press&#227;o arterial &#40;na consulta e na monitoriza&#231;&#227;o ambulat&#243;ria &#91;ABPM&#93;&#41; e da ACR foram inclu&#237;dos no presente estudo&#46; A idade m&#233;dia foi de 65&#177;7 anos&#44; 52&#37; do sexo feminino&#46; A maioria da popula&#231;&#227;o tinha diagn&#243;stico de HTN h&#225; &#62;10 anos&#44; 71&#37; tinha diabetes tipo 2 e 33&#37; tinham doen&#231;a vascular em pelo menos um territ&#243;rio&#46; A taxa de filtra&#231;&#227;o glomerular estimada foi de 73&#44;6&#177;25&#44;1 ml&#47;min&#47;1&#44;73 m<span class="elsevierStyleSup">2</span> e 48&#37; &#40;15 doentes&#41; tinham uma ACR&#62;30 mg&#47;g&#46; Aos 12 meses de seguimento&#44; 22 doentes foram considerados respondedores na press&#227;o arterial &#40;73&#37;&#41;&#46; A ACR teve uma descida significativa de uma mediana de 25&#44;8 mg&#47;g &#40;IQR 9&#44;0-574&#44;0 mg&#47;g&#41; para 14&#44;8 mg&#47;g &#40;IQR 4&#44;5-61&#44;0 mg&#47;g&#44; p&#61;0&#44;007&#41;&#46; Quando os resultados foram divididos em subgrupos&#44; de acordo com o estado de respondedor &#224; press&#227;o arterial na ABPM&#44; verificou-se uma redu&#231;&#227;o significativa nos respondedores &#40;de 25&#44;6 mg&#47;g &#91;IQR 8&#44;7-382&#44;8 mg&#47;g&#93; para 15&#44;9 mg&#47;g &#91;IQR 4&#44;4-55&#44;0 mg&#47;g&#93;&#44; p&#61;0&#44;009&#41;&#44; e uma tend&#234;ncia no subgrupo de n&#227;o respondedores &#40;de 165&#44;0 mg&#47;g &#91;IQR 8&#44;8-1423&#44;5 mg&#47;g&#93; para 13&#44;6 mg&#47;dl &#91;IQR 5&#44;7-1417&#44;0 mg&#47;g&#93;&#44; p&#61;0&#44;345&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclus&#227;o</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Para al&#233;m da descida significativa da press&#227;o arterial &#40;quer na consulta quer na monitoriza&#231;&#227;o ambulat&#243;ria de 24 h&#41;&#44; a desnerva&#231;&#227;o renal associou-se a uma redu&#231;&#227;o significativa da ACR&#44; um reconhecido marcador de les&#227;o de &#243;rg&#227;o alvo na hipertens&#227;o arterial&#46;</p></span>"
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            "titulo" => "Introdu&#231;&#227;o"
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            "titulo" => "Objetivo"
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            "titulo" => "M&#233;todos e resultados"
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            "titulo" => "Conclus&#227;o"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Flowchart of patient selection&#46; Of the total number of patients observed in an outpatient hypertension clinic &#40;n&#61;318&#41;&#44; 253 were excluded for various reasons &#40;see main text&#41; and 65 underwent renal denervation&#46; Of these 65&#44; complete 12-month follow-up with ambulatory blood pressure monitoring and transthoracic echocardiographic data were available in 31 patients&#46; ABPM&#58; 24-h ambulatory blood pressure monitoring&#59; ACR&#58; albumin-to-creatinine ratio&#59; BP&#58; blood pressure&#59; eGFR&#58; estimated glomerular filtration rate&#59; RDN&#58; renal denervation&#46;</p>"
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Values of albumin-to-creatinine ratio and estimated glomerular filtration rate at 12 months after renal denervation&#46; There was a significant reduction in the median values of ACR and the percentage of patients with ACR &#62;30 mg&#47;g&#44; without significant changes in eGFR&#46; ACR&#58; albumin-to-creatinine ratio&#59; eGFR&#58; estimated glomerular filtration rate&#46;</p>"
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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Percentages of patients in the different albumin-to-creatinine ratio subgroups&#46; There was a numerical decrease in the percentage of patients with an ACR &#62;300 mg&#47;g and an increase in patients with normal urinary albumin excretion between baseline and 12-month follow-up&#46; ACR&#58; albumin-to-creatinine ratio&#46;</p>"
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          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Values of albumin-to-creatinine ratio at 12 months after renal denervation in 24-h ambulatory blood pressure monitoring responder subgroups&#46; There was a significant reduction in median ACR in the BP responder subgroup&#44; and a numerical decrease in non-responders&#46; ACR&#58; albumin-to-creatinine ratio&#59; BP&#58; blood pressure&#46;</p>"
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          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Values of albumin-to-creatinine ratio at 12 months after renal denervation according to dipper status on 24-h ambulatory blood pressure monitoring&#46; There was a significant reduction in median ACR in the dipper subgroup&#44; and a numerical decrease in non-dippers&#46; ACR&#58; albumin-to-creatinine ratio&#46;</p>"
        ]
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        "etiqueta" => "Figure 6"
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          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Values of albumin-to-creatinine ratio at 12 months after renal denervation according to diabetic status&#46; There was a significant reduction in median ACR in patients with diabetes&#44; and a numerical decrease in the smaller subgroup of patients without diabetes&#46; ACR&#58; albumin-to-creatinine ratio&#46;</p>"
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          "leyenda" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">BMI&#58; body mass index&#59; CKD&#58; chronic kidney disease &#40;eGFR &#60;60 ml&#47;min&#47;1&#46;73 m<span class="elsevierStyleSup">2</span>&#41;&#59; eGFR&#58; estimated glomerular filtration rate&#59; RDN&#58; renal denervation&#59; RF&#58; radiofrequency&#46;</p>"
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                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Demographic and clinical variables</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Age &#40;years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">65&#177;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Male &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">15 &#40;48&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Caucasian &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">31 &#40;100&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Weight &#40;kg&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Height &#40;m&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>BMI &#40;kg&#47;m<span class="elsevierStyleSup">2</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">31&#46;8&#177;5&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Obesity &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">21 &#40;67&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Atrial fibrillation &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1 &#40;3&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Previous stroke &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2 &#40;6&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Type 2 diabetes &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">22 &#40;71&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Dyslipidemia &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">21 &#40;67&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Smoking &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1 &#40;3&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Sleep apnea &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5 &#40;19&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>eGFR &#40;ml&#47;min&#47;1&#46;73 m<span class="elsevierStyleSup">2</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">76&#46;4&#177;24&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>CKD &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5 &#40;16&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Hypertension &#62;10 years &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">28 &#40;90&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Coronary artery disease &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10 &#40;32&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Any vascular disease &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">11 &#40;35&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">RDN procedure</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Mean no&#46; of RF applications&#44; right renal artery&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#46;1&#177;1&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Mean no&#46; of RF applications&#44; left renal artery&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#46;7&#177;1&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Mean no&#46; of RF applications per patient&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10&#46;8&#177;2&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "leyenda" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">ACE&#58; angiotensin-converting enzyme&#59; ARB&#58; angiotensin receptor blockers&#46;</p>"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Baseline&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">12 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mean no&#46; of antihypertensive drugs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#46;8&#177;1&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#46;0&#177;1&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;002&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mean no&#46; of drug classes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#46;5&#177;0&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#46;9&#177;1&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ACE inhibitors&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">19 &#40;61&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">17 &#40;54&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;688&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ARBs &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">19 &#40;61&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">18 &#40;58&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Beta-blockers &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">26 &#40;83&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">27 &#40;87&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Calcium channel blockers &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">30 &#40;96&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">21 &#40;67&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;012&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Diuretics &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">27 &#40;87&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">24 &#40;77&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;727&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Spironolactone &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">23 &#40;74&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">26 &#40;83&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;453&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sympatholytics &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">22 &#40;71&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">19 &#40;61&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;508&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Aliskiren&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4 &#40;12&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;046&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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      8 => array:8 [
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        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
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          "leyenda" => "<p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">ABPM&#58; 24-h ambulatory blood pressure&#59; ACR&#58; albumin to creatinine ratio&#59; BP&#58; blood pressure&#59; bpm&#58; beats per minute&#59; DBP&#58; diastolic blood pressure&#59; eGFR&#58; estimated glomerular filtration rate&#59; SBP&#58; systolic blood pressure&#46;</p>"
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            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Baseline&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">12 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Office SBP &#40;mmHg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">176&#177;24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">149&#177;13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Office DBP &#40;mmHg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">90&#177;14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">79&#177;11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Heart rate &#40;bpm&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">73&#177;11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">70&#177;11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;261&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ABPM SBP &#40;mmHg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">150&#177;20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">132&#177;14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ABPM DBP &#40;mmHg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">83&#177;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">74&#177;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ABPM pulse pressure &#40;mmHg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">67&#177;18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">58&#177;13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ABPM mean BP &#40;mmHg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">105&#177;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">95&#46;3&#177;8&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ABPM heart rate &#40;bpm&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">67&#46;6&#177;9&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">65&#46;5&#177;9&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;090&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ABPM SBP responders<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">26 &#40;83&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Office SBP responders<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">22 &#40;71&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">-&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr></tbody></table>
                  """
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