Predictive Factors Affecting the Success of Nephrectomy for the Treatment of Nephrogenic Hypertension: Multicenter Study.

INTRODUCTION: The aim of our study is to evaluate the predictive factors affecting the success of treatment with nephrectomy in patients with poorly functioning kidney and nephrogenic hypertension. METHODS: Data for patients who underwent nephrectomy with a diagnosis of nephrogenic hypertension in 3 centers between May 2010 and January 2020 were analyzed. In the postoperative period, if the blood pressure (BP) was below 140/90 mm Hg without medical treatment, it was accepted as complete response; if the arterial BP was below 140/90 mm Hg with medical treatment or less medication, it was accepted as partial response; and if BP did not decrease to normal values, it was accepted as unresponsive. Demographic characteristics, duration of hypertension, preoperative and postoperative BP values, and presence of metabolic syndrome were statistically evaluated. RESULTS: Our study consisted of 91 patients with a mean preoperative hypertension duration of 23.3 ± 12.1 months. Among patients, 42 (46.2%) had complete response, 18 (19.8%) had partial response, and 31 (34.0%) had no response. Preoperative systolic and diastolic BP values were not effective on treatment success (p = 0.071, p = 0.973, respectively), but the increase in age and hypertension duration (p = 0.030 and p < 0.001, respectively) and the presence of metabolic syndrome (p = 0.002) significantly decreased the complete response rates. CONCLUSIONS: Preoperative hypertension duration, advanced age, and presence of metabolic syndrome are predictive factors affecting the response to treatment in patients who undergo nephrectomy due to nephrogenic hypertension.

Increase in Bioavailability of Nitric Oxide After Renal Denervation Improves Kidney Function in Sheep With Hypertensive Kidney Disease.

[Figure: see text].

Activated double-negative T cells (CD3+CD4-CD8-HLA-DR+) define response to renal denervation for resistant hypertension.

PURPOSE: To explore the cellular immune response of patients with resistant hypertension treated with renal denervation (RDN). METHODS AND RESULTS: Twenty-three patients were included and blood samples were obtained in six timings, pre and post procedure. Response was evaluated at six-months and one year and was observed in 69.6% and 82.6% of patients, respectively. Absolute values of HLA-DR+ double negative (DN) T cells were significantly lower in the group of 'responders' at one year, and interaction between the timings were found in three T cell subsets (T CD4, T CD8 and naïve T CD8 cells), with the 'responders' tending to present with lower absolute values and little inter-timing variation. CONCLUSIONS: 'Responders' significantly present with lower absolute values of activated DN T cells and have lower and more stable values of total T CD8+, CD4+, and naïve T CD8+ cells. These cell types may be able to predict response to RDN.

Renal sympathetic denervation for resistant hypertension: where do we stand after more than a decade / Denervação simpática renal para hipertensão resistente: situação depois de mais de uma década

Abstract Despite the current availability of safe and efficient drugs for treating hypertension, a substantial number of patients are drug-resistant hypertensives. Aiming this condition, a relatively new approach named catheter-based renal denervation was developed. We have now a clinically relevant time window to review the efficacy of renal denervation for treating this form of hypertension. This short review addresses the physiological contribution of renal sympathetic nerves for blood pressure control and discusses the pros and cons of renal denervation procedure for the treatment of resistant hypertension.

Resumo Em que pese a atual disponibilidade de medicamentos seguros e eficientes para o tratamento da hipertensão, um número significativo de pacientes sofre de hipertensão arterial resistente a tratamento medicamentoso. Em vista dessa condição, foi desenvolvida uma abordagem relativamente nova, denominada denervação renal por cateter. Dispomos atualmente de uma janela de tempo clinicamente relevante para analisar a eficácia da denervação renal no tratamento dessa modalidade de hipertensão. A presente revisão aborda a contribuição fisiológica dos nervos renais simpáticos no controle da pressão arterial e discute os prós e contras do procedimento de denervação renal no tratamento da hipertensão resistente.

Renal sympathetic denervation for resistant hypertension: where do we stand after more than a decade.

Despite the current availability of safe and efficient drugs for treating hypertension, a substantial number of patients are drug-resistant hypertensives. Aiming this condition, a relatively new approach named catheter-based renal denervation was developed. We have now a clinically relevant time window to review the efficacy of renal denervation for treating this form of hypertension. This short review addresses the physiological contribution of renal sympathetic nerves for blood pressure control and discusses the pros and cons of renal denervation procedure for the treatment of resistant hypertension.

Selective afferent renal denervation mitigates renal and splanchnic sympathetic nerve overactivity and renal function in chronic kidney disease-induced hypertension.

BACKGROUND: Clinical and experimental evidence have shown that renal denervation, by removing both the sympathetic and afferent nerves, improves arterial hypertension and renal function in chronic kidney disease (CKD). Given the key role of renal sympathetic innervation in maintaining sodium and water homeostasis, studies have indicated that the total removal of renal nerves leads to impaired compensatory mechanisms during hemodynamic challenges. METHOD: In the present study, we hypothesized that afferent (or sensory) fibers from the diseased kidney contribute to sympathetic overactivation to the kidney and other target organ, such as the splanchnic region, contributing to hypertension in CKD. We used a method to remove selectively the afferent renal fibers (periaxonal application of 33 mmol/l capsaicin) in a rat model of CKD, the 5/6 nephrectomy. RESULTS: Three weeks after afferent renal denervation (ARD), we found a decrease in mean arterial pressure (∼15%) and normalization in renal and splanchnic sympathetic nerve hyperactivity in the CKD group. Interestingly, intrarenal renin--angiotensin system, as well as renal fibrosis and function and proteinuria were improved after ARD in CKD rats. CONCLUSION: The findings demonstrate that afferent fibers contribute to the maintenance of arterial hypertension and reduced renal function that are likely to be mediated by increased sympathetic nerve activity to the renal territory as well as to other target organs in CKD.

Resistant Hypertension and Atherosclerotic Renal Artery Stenosis: Effects of Angioplasty on Ambulatory Blood Pressure. A Retrospective Uncontrolled Single-Center Study.

The effect of renal artery angioplasty on blood pressure in patients with true resistant hypertension and atherosclerotic renal artery stenosis has not been fully investigated due to the exclusion of these patients from most trials. In this study, we assessed the benefits of renal angioplasty on daytime ambulatory blood pressure (dABP) in this subgroup of patients. Medical records of our hypertension department were retrospectively analyzed from 2000 to 2016. Seventy-two patients were identified with resistant hypertension (dABP >135 or 85 mm Hg despite at least 3 antihypertensive drugs, including a diuretic) and atherosclerotic renal artery stenosis treated by angioplasty. Atherosclerotic renal artery stenosis was unilateral in 57 patients and bilateral in 15 patients. The mean age of the patients was 67.8±11.2 years; dABP was 157±16/82±10 mm Hg despite 4.0±1.0 antihypertensive treatments; estimated glomerular filtration rate was 52 (41-63) mL/min. After renal angioplasty, dABPM decreased by 14.0±17.3/6.4±8.7 mm Hg (P<0.001 for both), and the number of antihypertensive treatments decreased to 3.6±1.4 (P=0.002) with no significant change in estimated glomerular filtration rate. A high baseline systolic dABP and a low body mass index were independent predictors of systolic dABP changes. The decrease in dABP was confirmed in a subgroup of patients at one and 3 years of follow-up (N=31 and N=18 respectively, P≤0.001 for systolic and diastolic blood pressure at both visits). In this retrospective uncontrolled single-center study, angioplasty in patients with atherosclerotic renal artery stenosis and with true resistant hypertension significantly decreased dABP, reducing the need for antihypertensive treatment with no change in estimated glomerular filtration rate.

Renal sensory nerves increase sympathetic nerve activity and blood pressure in 2-kidney 1-clip hypertensive mice.

Renal denervation lowers arterial blood pressure (ABP) in multiple clinical trials and some experimental models of hypertension. These antihypertensive effects have been attributed to the removal of renal afferent nerves. The purpose of the present study was to define the function, anatomy, and contribution of mouse renal sensory neurons to a renal nerve-dependent model of hypertension. First, electrical stimulation of mouse renal afferent nerves produced frequency-dependent increases in ABP that were eliminated by ganglionic blockade. Stimulus-triggered averaging revealed renal afferent stimulation significantly increased splanchnic, renal, and lumbar sympathetic nerve activity (SNA). Second, kidney injection of wheat germ agglutinin into male C57Bl6 mice (12-14 wk; Jackson Laboratories) produced ipsilateral labeling in the T11-L2 dorsal root ganglia. Next, 2-kidney 1-clip (2K1C) hypertension was produced in male C57Bl6 mice (12-14 wk; Jackson Laboratories) by placement of a 0.5-mm length of polytetrafluoroethylene tubing around the left renal artery. 2K1C mice displayed an elevated ABP measured via telemetry and a greater fall in mean ABP to ganglionic blockade at day 14 or 21 vs. day 0. Renal afferent discharge was significantly higher in 2K1C-clipped vs. 2K1C-unclipped or sham kidneys. In addition, 2K1C-clipped vs. 2K1C-unclipped or sham kidneys had lower renal mass and higher mRNA levels of several proinflammatory cytokines. Finally, both ipsilateral renal denervation (10% phenol) or selective denervation of renal afferent nerves (periaxonal application of 33 mM capsaicin) at time of clipping resulted in lower ABP of 2K1C mice at day 14 or 21. These findings suggest mouse renal sensory neurons are activated to increase SNA and ABP in 2K1C hypertension. NEW & NOTEWORTHY This study documents the function, anatomy, and contribution of mouse renal sensory nerves to neurogenic hypertension produced by renal stenosis. Activation of renal afferents increased sympathetic nerve activity and blood pressure. Renal afferent activity was elevated in hypertensive mice, and renal afferent denervation lowered blood pressure. Clinically, patients with renal stenosis have been excluded from clinical trials for renal denervation, but this study highlights the potential therapeutic efficacy to target renal nerves in these patients.

Resistant hypertension.

The publication of the first non-randomised proof-of-concept trial of renal denervation as a treatment modality in treatment- -resistant hypertension set the stage for a search for novel devices with the expectation that technology would reduce the burden of hypertension by reducing or eliminating the costly and lifelong use of blood pressure-lowering medications. As we demonstrate in this review, this idea was so attractive to manufacturers and invasive cardiologists and radiologists that they overlooked decades of careful pathophysiological research in a disease that remains enigmatic but is still a major cause of cardio-vascular mortality worldwide. To make our point, we first reviewed the prevalence and risks associated with treatment-resistant hypertension. Next, we highlighted the key points required for the diagnosis of treatment-resistant hypertension, including the recording of ambulatory blood pressure and the assessment of adherence to medication. Finally, we summarised new insights in the management of treatment-resistant hypertension by medication and devices as well as in future research. Throughout our review, we focused on new evidence that had become available since 2013. Our conclusion is that optimising medical treatment based on simple algorithms remains the state of the art in treatment-resistant hypertension.

The early outcomes of candidates with portopulmonary hypertension after liver transplantation.

BACKGROUND: Portopulmonary hypertension (PPH) was once regarded as a contraindicaton to liver transplantation (LT). However, growing evidence has indicated that PPH patients undergoing LT may show similar outcomes compared to those without PPH, and researchers have recommended it not be an absolute contraindication. Given this controversy, we aimed to identify and review the current evidence on this topic and to provide a comparison of the outcomes after LT between candidates with PPH and those without. METHODS: We systematically searched the MEDLINE, EMBASE and Cochrane Library databases for all studies that compared the outcomes of PPH patients and those without PPH after LT. All studies reporting outcomes of PPH patients versus those without PPH (Control) were further considered for inclusion in this meta-analysis. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to compare the pooled data between PPH and Control groups. RESULTS: Eleven retrospective trials and one prospective, randomized, controlled trial, involving 37,686 transplant recipients were included. The PPH patients had increased 1-year mortality with an OR of 1.59 (95% CI = 1.26-2.01, P = 0.0001) compared to the control group. There was no significant difference in graft loss and 30-day mortality after LT between the two groups. CONCLUSIONS: Patients with PPH who underwent LT had increased 1-year mortality compared to those without PPH, while graft loss and 30-day mortality were similar. Nevertheless, LT may be a reasonable therapeutic option for some patients with PPH, but further studies are needed to identify those select patients with PPH who would benefit most from LT.

Extra-adrenal Pheochromocytoma Associated With Segmental Renal Artery Compression and Pseudostenosis.

Classically, pheochromocytomas and paragangliomas result in hypertension secondary to an excess release of catecholamines. However, when the tumor arises near the renal hilum, hypertension may also be secondary to renal artery stenosis, which can occur via several purported mechanisms. We describe an unusual case of a hereditary, extra-adrenal pheochromocytoma causing right lower pole renal artery pseudostenosis, pertinent radiologic signs, relevant surgical findings, and subsequent resolution after extirpative surgery.

Predictive factors for successful renal denervation: should we use them in clinical trials?

Renal denervation (RDN) is facing various challenges to its initial claimed value in hypertension treatment. Major concerns are the choice of the patients and the technical efficacy of the RDN. Different factors have been described as predicting the capacity of RDN to decrease blood pressure. These factors are related to the patients, the procedure and the tools to confirm successful neural ablation. Their use in future trials should help to improve RDN trials understanding and outcomes. This review summarizes the different predictive factors available and their potential benefits in patient selection and in procedure guidance.

Blood pressure reduction in patients with accessory renal arteries and bilateral single renal arteries after catheter-based renal denervation: a prospective study with 3-year follow-up.

INTRODUCTION: Catheter­based renal denervation (RD) is an effective treatment leading to a significant reduction of systolic and diastolic blood pressure (BP) in patients with resistant hypertension. OBJECTIVES: The aim of this prospective study was to assess the BP-lowering and pulse pressure (PP)- lowering effects in patients with accessory and bilateral single renal arteries after catheter­based RD during a 3­year follow­up. PATIENTS AND METHODS: The study included 31 patients with diagnosed resistant hypertension. Patients were classified into 2 groups: group 1 included patients with accessory renal arteries, and group 2, with bilateral single renal arteries. The BP and PP reduction levels were measured before the procedure and at 6, 12, 24, and 36 months after the procedure. RESULTS: All procedures were successful. In group 1, mean systolic BP, diastolic BP, and PP at baseline were 172.7 mm Hg, 98.9 mm Hg, and 74.4 mm Hg, respectively. Systolic BP, diastolic BP, and PP reduction levels were, respectively, -26.9, 19.2, and 7.5 at 6 months; -33.3, 16.1, and 16.4 at 12 months; -29.2, 14, and 18.2 at 24 months; and -28.6, 13.6, and 13.7 at 36 months. In group 2, mean systolic BP, diastolic BP, and PP at baseline were 175.6 mm Hg, 100.1 mm Hg, and 75.5 mm Hg, respectively. Systolic BP, diastolic BP, and PP reduction levels were, respectively, -26, 10.5, and 15.5 at 6 months; -22, 8.9, and 13 at 12 months; -28, 12.4, and 15.6 at 24 months; and -24.6, 14.97, and 9.2 at 36 months. Significant reductions were observed for systolic BP in group 1 and for PP and systolic and diastolic BP in group 2. CONCLUSIONS: RD successfully reduced systolic BP in patients with resistant hypertension and accessory renal arteries. PP reduction after RD in patients with accessory renal arteries was less pronounced than in patients with bilateral single renal arteries.

Reduced blood pressure-lowering effect of catheter-based renal denervation in patients with isolated systolic hypertension: data from SYMPLICITY HTN-3 and the Global SYMPLICITY Registry.

Aims: Catheter-based renal artery denervation (RDN) has been shown to lower blood pressure (BP) in certain patients with uncontrolled hypertension. Isolated systolic hypertension (ISH) (systolic BP [SBP] ≥140 mmHg and diastolic BP <90 mmHg), characterized by increased vascular stiffness, is the predominant hypertensive phenotype in elderly patients. This study compared baseline characteristics and SBP change at 6 months between patients with ISH and combined systolic­diastolic hypertension (CH). Methods and Results: This study pooled data from 1103 patients from SYMPLICITY HTN-3 and the Global SYMPLICITY Registry. A total of 429 patients had ISH, and 674 had CH. Patients with ISH were significantly older than those with CH (66 vs. 55 years), had more type 2 diabetes mellitus (52.9 vs. 34.6%), and a lower estimated glomerular filtration rate (71.8 vs. 78.6 mL/min/1.73 m2); all P < 0.001. At 6 months, the SBP drop for CH patients was −18.7 ± 23.7 mmHg compared with a reduction of −10.9 ± 21.7 mmHg for ISH patients −7.8 mmHg, 95% confidence interval, CI, −10.5, −5.1, P < 0.001). The change in 24-h SBP at 6 months was −8.8 ± 16.2 mmHg in patients with CH vs. −5.8 ± 15.4 mmHg in ISH (−3.0 mmHg, 95% CI −5.4, −0.6, P = 0.015). Presence of ISH at baseline but not age was associated with less pronounced BP changes following the procedure. The strongest predictor of office SBP reduction at 6 months was CH, followed by aldosterone antagonist use and non-use of vasodilators. Conclusion: The reduction in BP among patients with ISH following RDN was less pronounced than the reduction in patients with CH. Clinical.trials.gov Identifiers: NCT01534299 and NCT01418261.

Renal denervation in the most serious form of resistant arterial hypertension.

The aim of our observation was to establish whether or not renal sympathetic denervation (RSD) may help control blood pressure (BP) levels in patients with severe hypertension refractory to pharmacological therapy. Out of a group of 12 patients, candidates for RSD, with uncontrolled hypertension and a systolic BP over 190 mm Hg on repeated measurements despite optimal medication, four patients were excluded for multiple renal arteries and one for hyperaldosteronism. Seven patients had RSD using a Symplicity device (5M, 2 F) with a mean age of 64.9 years. While all were followed up for a minimum of 6 months, follow-up duration in the majority of them was substantially longer (12-20 months). At six months post-RSD, six of the seven patients showed a decrease in systolic BP by at least 15 mm Hg while receiving the same or fewer doses of antihypertensive agents. A similar response was seen in diastolic BP. The BP decrease was maintained throughout whole follow-up. In a small group of patients with severe hypertension, we demonstrated that renal sympathetic denervation is capable of reducing blood pressure even in patients with severe hypertension.

First report of monomicrobial Candida parapsilosis necrotizing fasciitis.

Candida parapsilosis is an emerging pathogen worldwide. It commonly causes soft tissue infection; however, to our knowledge there has been no previous report of monomicrobial necrotizing soft tissue infection (NSTI) secondary to C. parapsilosis. We report the first case of NSTI caused by C. parapsilosis in an immunocompromised renal transplant patient, with the diagnosis proven both histologically and microbiologically. Our patient required aggressive surgical intervention and antifungal therapy, with postoperative survival at 90 days.

Renal Sympathetic Denervation: Hibernation or Resurrection?

The most current versions of renal sympathetic denervation have been invented as minimally invasive approaches for the management of drug-resistant hypertension. The anatomy, physiology and pathophysiology of renal sympathetic innervation provide a strong background supporting an important role of the renal nerves in the regulation of blood pressure (BP) and volume. In addition, historical data with surgical sympathectomy and experimental data with surgical renal denervation indicate a beneficial effect on BP levels. Early clinical studies with transcatheter radiofrequency ablation demonstrated impressive BP reduction, accompanied by beneficial effects in target organ damage and other disease conditions characterized by sympathetic overactivity. However, the failure of the SYMPLICITY 3 trial to meet its primary efficacy end point raised a lot of concerns and put the field of renal denervation into hibernation. This review aims to translate basic research into clinical practice by presenting the anatomical and physiological basis for renal sympathetic denervation, critically discussing the past and present knowledge in this field, where we stand now, and also speculating about the future of the intervention and potential directions for research.

An update on renal artery denervation and its clinical impact on hypertensive disease.

Hypertension is a globally prevalent condition, with a heavy clinical and economic burden. It is the predominant risk factor for premature cardiovascular and cerebrovascular disease, and is associated with a variety of clinical disorders including stroke, congestive cardiac failure, ischaemic heart disease, chronic renal failure, and peripheral arterial disease. A significant subset of hypertensive patients have resistant hypertensive disease. In this group of patients, catheter-based renal artery denervation has emerged as a potential therapy, with favourable clinical efficacy and safety in early trials. Additional benefits of this therapy are also being identified and include effects on left ventricular remodeling, cardiac performance, and symptom status in congestive cardiac failure. Utility of renal denervation for the management of resistant hypertension, however, has become controversial since the release of the Symplicity HTN-3 trial, the first large-scale blinded randomised study investigating the efficacy and safety of renal artery denervation. The aim of this paper is to evaluate the history, utility, and clinical efficacy of renal artery denervation technology, including an in-depth appraisal of the current literature and principal trials.