Renal nerve ablation for hypertensive patients with chronic kidney disease.

Among current epidemics, chronic kidney disease (CKD) is accompanied with high morbidity and mortality rates inherently associated with the thriving comorbidities of hypertension and cardiovascular disease. In this mutually reinforcing triad, adequate control of high blood pressure emerges as extremely important for decreasing patients' complication rates and prolonging life expectancy. However, hypertension control in this particular group of patients is often proven an arduous task, presenting high rates of resistance. Sympathetic nervous system (SNS) overactivity is implicated not only in the pathophysiological basis of difficult-to-treat hypertension, but also in the development and progression of renal disease, thus rendering SNS a prime therapeutic target in CKD. As renal nerve ablation (RNA) is finding its place among other invasive procedures in the cardiovascular arena, the potential therapeutic impact of this innovative treatment modality is gradually expanding from resistant hypertension to other high blood pressure-related clinical conditions like CKD. Encouraging results of clinical trials testing efficacy and safety of renal nerve ablation in resistant hypertensives provide the opportunity to apply the procedure in other subgroups of hypertensive patients. Available data regarding renal function of study participants suggest the safe implementation of RNA in patients with renal disease, but both unexplored benefits as well as potential hazards should be taken into account and critically evaluated. While renal denervation has been tested in selected cases of patients with renal disease, the results of large, multicenter trials evaluating the effects of this procedure on large cohorts of patients with CKD are eagerly anticipated.

The role of renal nerve ablation for the management of resistant hypertension and other disease conditions: benefits and concerns.

The sympathetic nervous system is overactivated in resistant hypertension and several other disease conditions. A reciprocal association between the brain and the kidney has been described, in that sympathetic overactivity affects renal function while renal injury stimulates central sympathetic drive. Renal nerve ablation has been recently introduced as a potential alternative for the management of resistant hypertension, mainly due to current limitations in pharmacologic antihypertensive therapy. Data accumulated thus far point towards an efficacious and safe interventional method for the management of treatment resistance, with additional benefits on glucose metabolism and cardiac structure and function. Furthermore, beneficial effects have been observed in patients with chronic kidney disease, obstructive sleep apnea, polycystic ovary syndrome, and sympathetically driven tachyarrhythmias. However, as with every novel technique, several questions need to be answered and concerns need to be addressed before the wide application of this interventional approach.

Carotid baroreceptor stimulation: a promising approach for the management of resistant hypertension and heart failure.

Many difficult-to-treat clinical entities in the cardiovascular field are characterized by pronounced sympathetic overactivity, including resistant hypertension and heart failure, underlining the need to explore therapeutic options beyond pharmacotherapy. Autonomic modulation via carotid baroreceptor activation has already been evaluated in clinical trials for resistant hypertension, and relevant outcomes with regard to safety and efficacy of the technique are critically presented. The pathophysiological background of heart failure renders carotid baroreceptor stimulation a potential treatment candidate for the disease. Available data from animal models with heart failure point towards significant cardioprotective benefits of this innovative technique. Accordingly, the effects of baroreceptor activation treatment (BAT) on cardiac parameters of hypertensive patients are well-promising, setting the basis for upcoming clinical trials with baroreflex activation on patients with heart failure. However, as the potential therapeutic of BAT unfolds and new perspectives are highlighted, several concerns are raised that should be meticulously addressed before the wide application of this invasive procedure is set in the limelight.

A worldwide survey to assess the current approach to the treatment of patients with cancer and venous thromboembolism.

Low-molecular-weight heparin (LWMH) is recommended as the preferred anticoagulant treatment over vitamin K antagonists (VKA) for venous thromboembolism (VTE) in patients with cancer. However, there is uncertainty about the duration and dose of LMWH treatment. Therefore, we designed this multinational survey to assess the current approach to the treatment of patients with cancer and VTE. An electronic survey tool was used to disseminate a survey containing 49 questions on different aspects of the treatment of patients with cancer and VTE, among both thrombosis and non-thrombosis specialists. A total of 229 invitations were sent, and 141 completed the survey (60% of the total). Fifty-eight percent of the respondents were from Europe, 35% from the US and the remaining 7% from other countries. Respondent's specialties included haematology (23%), oncology (18%), pulmonology (15%) and general internal medicine (15%). LMWH was indicated as the first choice for the long-term treatment by 82% of the respondents, of whom 60% used full therapeutic doses and 40% chose a dose reduction. When continuing anticoagulants after the long-term treatment period, 44% of respondents preferred LMWH, 10% VKA, while the remaining 45% chose per individual patient for either LMWH or VKA. In conclusion, we observed a relatively high observance rate of the guidelines with respect to the use of LMWH for the long-term treatment of VTE in cancer. In contrast, the dose of LMWH and the type of anticoagulant chosen after the initial 3-12 months varied substantially, probably reflecting the limited available evidence.

Clinical studies of renal nerve ablation. Unanswered questions for its efficacy and safety.

Resistant hypertension is frequently encountered and remains challenging in everyday clinical practice despite the availability of numerous effective antihypertensive drugs. Existing limitations in drug therapy renders renal nerve ablation (RNA) an attractive alternative for the management of resistant hypertension. RNA has been proven so far both effective and safe in small clinical studies. However, every novel technique raises several questions that need to be answered before the wide application of this approach. Likewise, existing data with RNA leave some unanswered questions, which among others include: the heterogeneity in blood pressure response, the identification of response predictors, the extent of RNA, the association between office and ambulatory blood pressure reduction, the long-term efficacy and safety of the procedure, the time-course of blood pressure response, and the effects on renal function in the long-term. This review aims to discuss these issues since RNA represents one of the hottest topics in hypertension and research directions are urgently needed.

Loss of striatal DA innervation increases striatal trophic activity directed at DA neurons in culture.

Male rats received intraventricular infusions of the dopamine (DA) neurotoxin 6-hydroxydopamine (6-OHDA; 0, 75, 150, and 250 micrograms) in order to determine if DA neuron loss was associated with an increase in striatal trophic activity. After 4 weeks, the animals were sacrificed and perfused with normal saline, and the brains were removed, immediately frozen, and processed. Intraventricular infusions of 6-OHDA were associated with a dose-dependent reduction in striatal DA content and tyrosine hydroxylase-immunoreactive (THir) cell counts in the substantia nigra while striatal DA activity ([HVA]/[DA]) was increased. Extracts of the striatum from these animals increased the survival of E15 primary, dissociated rostral mesencphalic cultures growing at low cell density. This growth effect was positively correlated with the dose of 6-OHDA infused. THir cell counts present in high-cell-density mesencephalic cultures following 72 h of extract incubation were similarly correlated to 6-OHDA dose but inversely correlated with striatal DA content and THir cell counts in the substantia nigra. Trophic activity in the cerebellar extracts from these animals was significantly lower than that present in striatal extracts and was not influenced by 6-OHDA lesions. These data suggest that loss of DA innervation in the striatum is associated with an increase in striatal trophic activity directed at DA neurons. A compensatory response to the loss of DA neurons involving increased striatal trophic activity may result in increased DA terminal sprouting of remaining viable DA neurons that, in turn would serve to help reinstate normal DA tone.

Cerebrospinal fluid from patients with Parkinson's disease alters the survival of dopamine neurons in mesencephalic culture.

We have previously demonstrated that extracts of striatal tissue from patients with Parkinson's disease (PD) increase the survival of dopamine neurons in mesencephalic cultures relative to striatal extracts from control patients. In the present study, ventricular cerebrospinal fluid (vCSF) from patients with PD, Alzheimer's disease (AD), and age-matched controls was similarly assessed. vCSF samples were separated into > 10-kDa and < 10-kDa fractions. Cultures incubated with the > 10-kDa fractions from PD and AD patients contained 73 and 13%, respectively, more tyrosine hydroxylase immunoreactive neurons than cultures incubated with vCSF from age-matched controls. This trophic activity was positively correlated with the trophic activity present in striatal extracts from the same patients. The < 10-kDa vCSF fractions from all patient groups inhibited culture growth. These data suggest that the trophic environment in the striatum is altered in PD and can be successfully monitored in CSF.