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    "textoCompleto" => "<p class="elsevierStylePara">Although the therapeutic management of arterial hypertension &#40;AHT&#41;&#44; which is a public health issue due to its importance in terms of patient health and socioeconomic impacts&#44; has improved somewhat in Spain&#44;<span class="elsevierStyleSup">1&#44;2</span> there are still substantial gaps in our ability to control this entity&#46;</p><p class="elsevierStylePara">Non-compliance&#44; therapeutic inertia&#44; insufficient or inadequate anti-hypertensive treatment&#44; and the characteristics inherent to each form of AHT are recognised as factors that contribute to the inadequate control of AHT&#44; and the consequent increase in vascular morbidity and mortality rates&#46;</p><p class="elsevierStylePara">One of the forms of AHT that implies the highest rates of morbidity and mortality&#44; in addition to increased direct and indirect costs derived from diagnosis and treatment&#44; is refractory or resistant AHT &#40;defined as AHT in which&#44; 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and the prescription of multiple combinations &#40;5 or more&#41; of anti-hypertensive drugs with complementary mechanisms of action at appropriate doses&#44; approximately 2&#37;-4&#37; of hypertensive patients do not have their blood pressure &#40;BP&#41; under control&#44; with values surpassing 140mm Hg&#44; and a very high risk of target organ damage and&#47;or developing vascular complications&#46;<span class="elsevierStyleSup">3&#44;4</span></p><p class="elsevierStylePara">In recent years&#44; the search for cost-effective solutions for managing these patients has expanded into non-pharmacological treatment alternatives&#58; one of these is based on radio-frequency ablation of the afferent and efferent sympathetic nerves of the renal arteries &#40;renal sympathetic denervation &#91;RSDN&#93;&#41;&#44;<span class="elsevierStyleSup">6</span> and another one is based on parasympathetic activation of the carotid baroreceptors through electrical stimulation &#40;Rheos<span class="elsevierStyleSup">&#174;</span> system&#41;&#46;<span class="elsevierStyleSup">7</span> In conjunction with anti-hypertensive medication&#44; both techniques appear to produce positive results&#44; reaching a significantly better control of BP in these cases of severe refractory hypertension&#59; however&#44; the ease of technical application makes RSDN the most commonly used technique with the greatest basis in clinical evidence&#46;<span class="elsevierStyleSup">8</span></p><p class="elsevierStylePara">What are the rational bases for using RSDN as a treatment alternative in severe refractory hypertension patients&#63; The fundamental basis of this treatment strategy is the central role that sympathetic hyperactivity plays in the development and maintenance of AHT&#44; as well as in contributing to structural vascular and organ damage&#44; along with altered carbohydrate and lipid metabolism&#46;<span class="elsevierStyleSup">9</span> In addition&#44; the afferent and efferent renal sympathetic nerves contribute to the increase in sympathetic activity&#46; Through the sympathetic nervous system&#44; the kidneys actively participate in modulating sympathetic activity&#44; both in the development of AHT and its cardiovascular complications&#46;<span class="elsevierStyleSup">10&#44;11</span> Finally&#44; the cost-effectiveness and the usefulness of RSDN as a coadjuvant therapy along with anti-hypertensive medication for refractory AHT is evidenced by the clinical benefits &#40;better control of BP&#41; derived from the application of this treatment to more than 5000 patients to date&#46;<span class="elsevierStyleSup">12</span></p><p class="elsevierStylePara">Data from the clinical trials Simplicity HTN-1<span class="elsevierStyleSup">13&#44;14</span> and Simplicity HTN-2<span class="elsevierStyleSup">15</span> show the short-term and long-term &#40;up to 36 months&#41;<span class="elsevierStyleSup">16</span> anti-hypertensive effects and safety of this therapeutic approach&#46;</p><p class="elsevierStylePara">The results from the Simplicity HTN-1&#44; the first non-randomised clinical trial that initially included only 45 patients with refractory hypertension&#44; showed a mean decrease in systolic and diastolic BP of -25mm Hg and -12mm Hg&#44; respectively&#44; after 6 months on the treatment protocol&#46; When the sample size of this study was amplified to 153 patients&#44;<span class="elsevierStyleSup">14</span> the mean decreases in systolic and diastolic BP were -32mm Hg and -14mm Hg&#44; respectively&#44; after 2 years of follow-up&#44; and BP control &#40;&#60;140&#47;90mm HG&#41; at 39&#37; after 12 months&#44; which remained unchanged 2 years later and was even accompanied by an increase in the initial number of non-responsive patients&#46;<span class="elsevierStyleSup">14</span> These results are accompanied by an excellent safety profile&#44; with only 3&#37; of treated patients developing some kind of secondary side effect in the form of one case of renal artery dissection and another case of progression of a prior renal artery stenosis&#46;<span class="elsevierStyleSup">13</span></p><p class="elsevierStylePara">Equally significant results were obtained by the Simplicity HTN-2&#44;<span class="elsevierStyleSup">14</span> which was a 1&#58;1 randomised study &#40;test group&#58; control group&#41; including 106 hypertensive patients that were refractory to treatment with 5 or more anti-hypertensive drugs at high doses&#46; As compared to the control group&#44; which did not significantly vary in its BP values&#44; the patients that underwent RSDN had progressive decreases in BP until reaching a mean decrease of systolic and diastolic BP of -32mm Hg and -12mm HG&#44; respectively&#44; after 12 months&#46; After only 6 months&#44; 39&#37; of test patients already had a systolic BP&#60;140mm Hg&#44; and 20&#37; required a decrease in anti-hypertensive medication dosage&#46;<span class="elsevierStyleSup">15</span> However&#44; 10&#37; of patients received no benefit from RSDB&#44; with the mean decrease in systolic BP lower than 10mm Hg&#46;<span class="elsevierStyleSup">15</span> Along this same topic&#44; the current issue of <span class="elsevierStyleItalic">Nefrolog&#237;a </span>presents a clinical case of refractory AHT that was resistant to multiple anti-hypertensive drugs and that&#44; after undergoing RSDN&#44; an additional reduction in systolic and diastolic BP of -22mm Hg was achieved&#44; which without a doubt contributes to the mid-term and long-term decrease in the vascular risk of the patient&#46;</p><p class="elsevierStylePara">As regards the technique&#44; the application of the endovascular procedure is not complex&#58; a femoral approach is used to access both renal arteries&#44; and radiofrequency ablation is applied to the sympathetic innervation of these arteries every 5mm circumferentially from the distal zone to the ostial zone&#46; Even though the technique is quite simple&#44; it is not without its limitations and contraindications&#44;<span class="elsevierStyleSup">8</span> requiring a prior evaluation of the anatomy of the main renal arteries&#59; the procedure is contraindicated in the case of multiple renal arteries&#44; a principal renal artery with a diameter &#60;4mm or a length &#60;20mm&#44; and in cases of a previous stent or stenosis&#46; In addition&#44; this procedure is contraindicated in patients with type 1 diabetes&#44; an estimated glomerular filtration rate &#60;45ml&#47;min&#47;1&#46;73m<span class="elsevierStyleSup">2</span>&#44; unstable angina&#44; acute myocardial infarction&#44; or stroke within the last 3-6 months&#46;<span class="elsevierStyleSup">8</span></p><p class="elsevierStylePara">In addition to its anti-hypertensive effects&#44; preliminary studies show that RSDN appears to provide cardiovascular and metabolic benefits that go beyond its anti-hypertensive effects in sub-groups of hypertensive patients with sympathetic hyperactivity&#44; such as those with altered carbohydrate metabolism&#44; sleep apnoea syndrome&#44; heart failure&#44; chronic renal failure&#44; and hepatorenal syndrome&#46;<span class="elsevierStyleSup">8&#44;16-18</span> This is certainly a field open to investigation&#44; necessitating larger randomised studies to ascertain the possible mid-term and long-term benefits of this procedure&#46;</p><p class="elsevierStylePara">Apart from its limitations and contraindications&#44; a series of criteria for patient eligibility exists&#44; although these criteria are not completely well-defined&#44; for administering RSDN to patients with refractory hypertension&#46;</p><p class="elsevierStylePara">Without a doubt&#44; the first criteria is to rule out the existence of pseudo-resistance&#44; which requires a complete evaluation of the patient&#44; including confirming the resistance to standard treatment with an ambulatory BP measurement for 24 hours&#44; correcting exogenous factors that could maintain an elevated BP&#44; and certifying that the possibilities for controlling BP using combinations of multiple complementary anti-hypertensive drugs at high doses have been exhausted&#44;<span class="elsevierStyleSup">8</span> rather than being satisfied with a systolic BP &#8805;160mm Hg &#40;or &#8805;150mm Hg for diabetics&#41; and the use of 3 or more anti-hypertensive drugs&#44; as was initially proposed by certain authors&#46;<span class="elsevierStyleSup">4&#44;8</span> We also believe that in candidates for RSDN&#44; we must monitor damage indicators in affected organs that corroborate with the severity of AHT&#44;<span class="elsevierStyleSup">19</span> and that the cost-efficacy and cost-effectiveness of the procedure must be evaluated on an individual patient basis&#46;</p><p class="elsevierStylePara">It goes without saying that the procedure must be carried out in hospitals by personnel with sufficient experience in the management of these patients and these endovascular techniques&#46;<span class="elsevierStyleSup">8</span></p><p class="elsevierStylePara">Finally&#44; although the RSDN technique appears to be quite promising&#44; there are still unanswered questions referring to certain aspects such as the identification of direct predictors for treatment success&#44; testing the effectiveness of RSDN mid-procedure&#44; methods for evaluating a possible process of re-innervation&#44; evaluation of effects on target organs&#44; and the efficacy of other procedures that might produce denervation &#40;ultrasound&#44; micro-wave&#44; laser&#44; cryotherapy&#44; etc&#46;&#41;&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Conflicts of interest</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The authors have no conflicts of interest to declare&#46;</p>"
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Renal sympathetic denervation: a new treatment strategy in the management of refractory arterial hypertension
Denervación simpática de arterias renales: una nueva estrategia terapéutica en el manejo de la hipertensión arterial refractaria
Pedro Aranda-Laraa, M. Dolores Martínez-Estebana, José J. Muñozb, Domingo Hernández-Marreroa
a Unidad de HTA y Riesgo Vascular. Servicio de Nefrología, Hospital Regional Universitario Carlos Haya, Málaga,
b Servicio de Radiología Vascular Intervencionista, Hospital Regional Universitario Carlos Haya, Málaga,
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    "textoCompleto" => "<p class="elsevierStylePara">Although the therapeutic management of arterial hypertension &#40;AHT&#41;&#44; which is a public health issue due to its importance in terms of patient health and socioeconomic impacts&#44; has improved somewhat in Spain&#44;<span class="elsevierStyleSup">1&#44;2</span> there are still substantial gaps in our ability to control this entity&#46;</p><p class="elsevierStylePara">Non-compliance&#44; therapeutic inertia&#44; insufficient or inadequate anti-hypertensive treatment&#44; and the characteristics inherent to each form of AHT are recognised as factors that contribute to the inadequate control of AHT&#44; and the consequent increase in vascular morbidity and mortality rates&#46;</p><p class="elsevierStylePara">One of the forms of AHT that implies the highest rates of morbidity and mortality&#44; in addition to increased direct and indirect costs derived from diagnosis and treatment&#44; is refractory or resistant AHT &#40;defined as AHT in which&#44; despite a treatment based on the application of a series of diet restrictions and lifestyle changes along with the adequate use of at least 3 anti-hypertensive drugs &#8211;one of which must be a diuretic-&#44; blood pressure remains uncontrolled&#41;&#46;<span class="elsevierStyleSup">3&#44;4</span> Although no studies have been specifically designed to measure the prevalence of AHT in hypertensive patients&#44; the estimated prevalence is 10&#37;-15&#37;&#44;<span class="elsevierStyleSup">3&#44;5</span> with rates 2 times higher in certain sub-groups of hypertensive subjects&#44; such as obese patients&#44; diabetics&#44; chronic renal failure patients&#44; and sleep apnoea syndrome patients&#46;<span class="elsevierStyleSup">3&#44;4</span> Adequate treatment of these patients reduces significantly the percentage of cases of hypertension that are truly refractory to treatment&#46; Even so&#44; in spite of protocols involving detailed anamnesis and diagnostic measures&#44; the application of a gamut of hygienic&#47;dietetic methods for making heart-healthy changes in patient lifestyles&#44; and the prescription of multiple combinations &#40;5 or more&#41; of anti-hypertensive drugs with complementary mechanisms of action at appropriate doses&#44; approximately 2&#37;-4&#37; of hypertensive patients do not have their blood pressure &#40;BP&#41; under control&#44; with values surpassing 140mm Hg&#44; and a very high risk of target organ damage and&#47;or developing vascular complications&#46;<span class="elsevierStyleSup">3&#44;4</span></p><p class="elsevierStylePara">In recent years&#44; the search for cost-effective solutions for managing these patients has expanded into non-pharmacological treatment alternatives&#58; one of these is based on radio-frequency ablation of the afferent and efferent sympathetic nerves of the renal arteries &#40;renal sympathetic denervation &#91;RSDN&#93;&#41;&#44;<span class="elsevierStyleSup">6</span> and another one is based on parasympathetic activation of the carotid baroreceptors through electrical stimulation &#40;Rheos<span class="elsevierStyleSup">&#174;</span> system&#41;&#46;<span class="elsevierStyleSup">7</span> In conjunction with anti-hypertensive medication&#44; both techniques appear to produce positive results&#44; reaching a significantly better control of BP in these cases of severe refractory hypertension&#59; however&#44; the ease of technical application makes RSDN the most commonly used technique with the greatest basis in clinical evidence&#46;<span class="elsevierStyleSup">8</span></p><p class="elsevierStylePara">What are the rational bases for using RSDN as a treatment alternative in severe refractory hypertension patients&#63; The fundamental basis of this treatment strategy is the central role that sympathetic hyperactivity plays in the development and maintenance of AHT&#44; as well as in contributing to structural vascular and organ damage&#44; along with altered carbohydrate and lipid metabolism&#46;<span class="elsevierStyleSup">9</span> In addition&#44; the afferent and efferent renal sympathetic nerves contribute to the increase in sympathetic activity&#46; Through the sympathetic nervous system&#44; the kidneys actively participate in modulating sympathetic activity&#44; both in the development of AHT and its cardiovascular complications&#46;<span class="elsevierStyleSup">10&#44;11</span> Finally&#44; the cost-effectiveness and the usefulness of RSDN as a coadjuvant therapy along with anti-hypertensive medication for refractory AHT is evidenced by the clinical benefits &#40;better control of BP&#41; derived from the application of this treatment to more than 5000 patients to date&#46;<span class="elsevierStyleSup">12</span></p><p class="elsevierStylePara">Data from the clinical trials Simplicity HTN-1<span class="elsevierStyleSup">13&#44;14</span> and Simplicity HTN-2<span class="elsevierStyleSup">15</span> show the short-term and long-term &#40;up to 36 months&#41;<span class="elsevierStyleSup">16</span> anti-hypertensive effects and safety of this therapeutic approach&#46;</p><p class="elsevierStylePara">The results from the Simplicity HTN-1&#44; the first non-randomised clinical trial that initially included only 45 patients with refractory hypertension&#44; showed a mean decrease in systolic and diastolic BP of -25mm Hg and -12mm Hg&#44; respectively&#44; after 6 months on the treatment protocol&#46; When the sample size of this study was amplified to 153 patients&#44;<span class="elsevierStyleSup">14</span> the mean decreases in systolic and diastolic BP were -32mm Hg and -14mm Hg&#44; respectively&#44; after 2 years of follow-up&#44; and BP control &#40;&#60;140&#47;90mm HG&#41; at 39&#37; after 12 months&#44; which remained unchanged 2 years later and was even accompanied by an increase in the initial number of non-responsive patients&#46;<span class="elsevierStyleSup">14</span> These results are accompanied by an excellent safety profile&#44; with only 3&#37; of treated patients developing some kind of secondary side effect in the form of one case of renal artery dissection and another case of progression of a prior renal artery stenosis&#46;<span class="elsevierStyleSup">13</span></p><p class="elsevierStylePara">Equally significant results were obtained by the Simplicity HTN-2&#44;<span class="elsevierStyleSup">14</span> which was a 1&#58;1 randomised study &#40;test group&#58; control group&#41; including 106 hypertensive patients that were refractory to treatment with 5 or more anti-hypertensive drugs at high doses&#46; As compared to the control group&#44; which did not significantly vary in its BP values&#44; the patients that underwent RSDN had progressive decreases in BP until reaching a mean decrease of systolic and diastolic BP of -32mm Hg and -12mm HG&#44; respectively&#44; after 12 months&#46; After only 6 months&#44; 39&#37; of test patients already had a systolic BP&#60;140mm Hg&#44; and 20&#37; required a decrease in anti-hypertensive medication dosage&#46;<span class="elsevierStyleSup">15</span> However&#44; 10&#37; of patients received no benefit from RSDB&#44; with the mean decrease in systolic BP lower than 10mm Hg&#46;<span class="elsevierStyleSup">15</span> Along this same topic&#44; the current issue of <span class="elsevierStyleItalic">Nefrolog&#237;a </span>presents a clinical case of refractory AHT that was resistant to multiple anti-hypertensive drugs and that&#44; after undergoing RSDN&#44; an additional reduction in systolic and diastolic BP of -22mm Hg was achieved&#44; which without a doubt contributes to the mid-term and long-term decrease in the vascular risk of the patient&#46;</p><p class="elsevierStylePara">As regards the technique&#44; the application of the endovascular procedure is not complex&#58; a femoral approach is used to access both renal arteries&#44; and radiofrequency ablation is applied to the sympathetic innervation of these arteries every 5mm circumferentially from the distal zone to the ostial zone&#46; Even though the technique is quite simple&#44; it is not without its limitations and contraindications&#44;<span class="elsevierStyleSup">8</span> requiring a prior evaluation of the anatomy of the main renal arteries&#59; the procedure is contraindicated in the case of multiple renal arteries&#44; a principal renal artery with a diameter &#60;4mm or a length &#60;20mm&#44; and in cases of a previous stent or stenosis&#46; In addition&#44; this procedure is contraindicated in patients with type 1 diabetes&#44; an estimated glomerular filtration rate &#60;45ml&#47;min&#47;1&#46;73m<span class="elsevierStyleSup">2</span>&#44; unstable angina&#44; acute myocardial infarction&#44; or stroke within the last 3-6 months&#46;<span class="elsevierStyleSup">8</span></p><p class="elsevierStylePara">In addition to its anti-hypertensive effects&#44; preliminary studies show that RSDN appears to provide cardiovascular and metabolic benefits that go beyond its anti-hypertensive effects in sub-groups of hypertensive patients with sympathetic hyperactivity&#44; such as those with altered carbohydrate metabolism&#44; sleep apnoea syndrome&#44; heart failure&#44; chronic renal failure&#44; and hepatorenal syndrome&#46;<span class="elsevierStyleSup">8&#44;16-18</span> This is certainly a field open to investigation&#44; necessitating larger randomised studies to ascertain the possible mid-term and long-term benefits of this procedure&#46;</p><p class="elsevierStylePara">Apart from its limitations and contraindications&#44; a series of criteria for patient eligibility exists&#44; although these criteria are not completely well-defined&#44; for administering RSDN to patients with refractory hypertension&#46;</p><p class="elsevierStylePara">Without a doubt&#44; the first criteria is to rule out the existence of pseudo-resistance&#44; which requires a complete evaluation of the patient&#44; including confirming the resistance to standard treatment with an ambulatory BP measurement for 24 hours&#44; correcting exogenous factors that could maintain an elevated BP&#44; and certifying that the possibilities for controlling BP using combinations of multiple complementary anti-hypertensive drugs at high doses have been exhausted&#44;<span class="elsevierStyleSup">8</span> rather than being satisfied with a systolic BP &#8805;160mm Hg &#40;or &#8805;150mm Hg for diabetics&#41; and the use of 3 or more anti-hypertensive drugs&#44; as was initially proposed by certain authors&#46;<span class="elsevierStyleSup">4&#44;8</span> We also believe that in candidates for RSDN&#44; we must monitor damage indicators in affected organs that corroborate with the severity of AHT&#44;<span class="elsevierStyleSup">19</span> and that the cost-efficacy and cost-effectiveness of the procedure must be evaluated on an individual patient basis&#46;</p><p class="elsevierStylePara">It goes without saying that the procedure must be carried out in hospitals by personnel with sufficient experience in the management of these patients and these endovascular techniques&#46;<span class="elsevierStyleSup">8</span></p><p class="elsevierStylePara">Finally&#44; although the RSDN technique appears to be quite promising&#44; there are still unanswered questions referring to certain aspects such as the identification of direct predictors for treatment success&#44; testing the effectiveness of RSDN mid-procedure&#44; methods for evaluating a possible process of re-innervation&#44; evaluation of effects on target organs&#44; and the efficacy of other procedures that might produce denervation &#40;ultrasound&#44; micro-wave&#44; laser&#44; cryotherapy&#44; etc&#46;&#41;&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Conflicts of interest</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The authors have no conflicts of interest to declare&#46;</p>"
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Idiomas
Nefrología (English Edition)