Current Hypertension Reviews - Volume 8, Issue 4, 2012

Increased arterial stiffness is emerging as a useful marker of cardiovascular damage. A growing body of evidence suggests that the stiffening of the conduit arteries is linearly associated with poor survival in the general population and high-risk population such as Chronic Kidney Disease (CKD) patients. Indeed, the loss of the elastic properties of conduit arteries induces an increase in the central pulse pressure and cardiac workload leading to left ventricular hypertrophy and reduced coronary and capillary perfusion. Notably, all these changes are independent of mean blood pressure and other established cardiovascular risk factors. Though, evidence is still inconclusive, some preliminary data suggest that arterial stiffness and central blood pressure evaluation can be of use for risk stratification and treatment individualization. We herein summarize the current evidence supporting the usefulness of arterial stiffness assessment for CKD patients' management.

Sympathetic neural mechanisms are involved in the development and progression of hypertension. In the last few years the role of renal nerves as regulators of kidney function, volume homeostasis and blood pressure control and as potential target of therapeutic intervention has received renewed interest. Data obtained by the radiofrequency catheterbased procedure for renal denervation have provided evidence for a prolonged sympathoinhibitory and blood pressure lowering effect but also for a positive effect on metabolism and on target organ damage.

There is a global ESRD pandemic. Despite all therapeutic maneuvers and advances in dialysis care over the last two decades, ESRD patients on hemodialysis continue to experience high all-cause and cardiovascular mortality, with annual mortality rates exceeding 20%. There have been attempts to show that combination angiotensin converting enzyme inhibition and angiotensin receptor blockade therapy will help resolve this overwhelming cardiovascular mortality among hemodialysis patients. We present here, a balanced review of current knowledge on the benefits and pitfalls of the use of combination angiotensin converting enzyme inhibition and angiotensin receptor blockade in this vulnerable patient population. We conclude that there is no quick simple fix to the high cardiovascular mortality in hemodialysis patients. Combination angiotensin converting enzyme inhibition and angiotensin receptor blockade has not and will not solve the quagmire. Cardiovascular mortality among hemodialysis patients, clearly very high, is under the influence of just too many confounding factors and variables. Thus, in our mind, only through a concerted multifaceted approach, targeting all the variables discussed in this review, and more, and most importantly, with significant flexibility to individualize and tailor therapies as they are applicable and tolerated by specific individual patients, would we even begin to dent the high cardiovascular mortality among hemodialysis patients. A simple randomized placebo-controlled trial, just targeting one plausible etiologic factor, in our opinion, will hardly prove any more useful than previous such trials have demonstrated in the past.

Mineralocorticoid receptor (MR) blockade has proven efficacy in the treatment of hypertension and in improving morbidity and mortality in patients with heart failure. The potential importance of mineralocorticoid receptor blockade has grown recently amid the observation that angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers do not effectively reduce aldosterone levels in all patients over the long term. To date, research on the role of MR blockade has primarily focused on resistant hypertension, decreasing proteinuria, and potentially preventing disease progression in early stages of chronic kidney disease (CKD). Given the prevalence of co-morbid resistant hypertension and cardiovascular disease in patients with end-stage renal disease (ESRD), however, interest in the role of MR blockade in this patient population has arisen. In this paper, we review the current evidence for using MR blockade in mild-tomoderate and resistant hypertension in patients with normal renal function, CKD, and ESRD. We discuss recent animal and human studies on the role of aldosterone in mediating hypertension as well as vascular and tissue damage. We then review clinical studies on the use of MR blockade in ameliorating aldosterone’s deleterious end organ effects and its applicability to patients with ESRD. Finally, we summarize the evidence to date supporting the safety of MR blockade in patients with ESRD.

Blood pressure (BP) measurement is a simple, and reproducible methool and is easily accepted by patients. It is well known that in a single subject BP may change during the day; this fact is considered physiological by many physicians and does not influence the final estimated value of BP. However, it's reasonable to suppose that blood pressure variability (BPV) has clinical consequences and that exists a cardiovascular risk related to it. In fact, recent observations indicate that BP variations could be responsible for organ damage associated with hypertension more than the systolic and diastolic BP. In this study, we aim to analyze and compare published data in literature concerning the presumable correlations between BP variability and outcomes, both in Chronic Kidney Disease (CKD) and End stage Renal Disease (ESRD). We conclude that BPV represents an important cardiovascular risk factor for both patients with CKD and for those in dialysis. No correlations were found between BPV and the progression of CKD. However, this is a retrospective study and more (RCTS) are needed on this topic.

Hypertension occurring during the course of dialysis is an increasingly recognized finding in ESRD patients treated with hemodialysis. In this review, we will describe the epidemiologic, observational, and experimental studies that have increased our understanding of the natural history, health consequences, pathophysiology, and potential prevention and treatment strategies for intradialytic hypertension. The observational evidence has led to the development of definitions of intradialytic hypertension that are validated in longitudinal cohort studies and are predictive of future health consequences from untreated intradialytic hypertension. The epidemiologic studies have demonstrated that intradialytic hypertension occurs much more commonly in ESRD patients treated with hemodialysis than previously appreciated. A number of lines of evidence support the view that intradialytic hypertension is an important independent risk factor for cardiovascular disease and for premature death. This body of evidence is discussed in the context Hill criteria for causation where intradialytic hypertension might be considered a harmful exposure causally linked to the development of cardiovascular disease. The majority of the Hill criteria are met supporting the view of a causal link. A number of laboratories using experimental and translational models have begun to elucidate the mechanisms that may mediate the intradialytic hypertension observed in a subset of hemodialysis patients. We shall review the emerging understanding of the epidemiology and pathophysiology that has led to the identification and validation of biomarkers of vascular dysfunction and/or dysregulation in patients exhibiting intradialytic hypertension. We shall review the evidence from short-term experimental trials evaluating potential interventions to treat or prevent this condition. To date, these studies have evaluated the effects of interventions on biomarkers of vascular dysfunction, on hormonal mediators of endothelial tone, and on intra- and interdialytic blood pressures in the short term. We shall review recommendations that can be justified by this new evidence and the limitations of this evidence in informing treatment. The lack of long-term RCT patient-centered outcome studies is particularly problematic when attempting to estimate the long-term benefits from treatment. Current recommendations which remain largely empiric include those for more robust surveillance for intradialytic hypertension and for its treatment, more focus on avoidance of volume overload and on avoidance of significant electrolyte imbalances during hemodialysis where these fluid and electrolyte imbalances may cause intradialytic hypertension, and more selectivity in medication choice for the pharmacologic management of hypertension in dialysis patients.

Hemodialysis patients have a high cardiovascular mortality and hypertension is the most prevalent treatable risk factor. Hemodialysis is an unphysiological therapy respect to daily renal function, and the approach to avoid the related may be to increase dialysis frequency using a daily dialysis therapy. We analyze as the effect of more long or frequent weekly dialysis can improve the hypertension in hemodialysis patients.

Cardiovascular disease is one major cause of mortality and morbidity after renal transplantation. Management of arterial hypertension as one important risk factor is a complex problem in the ambulatory care for these patients. Offical therapeutical recommendations are vague and due to the lack of randomized controlled and prospective studies generally based on experiences in nontransplanted patient populations. New insights into different pathogenetic mechanisms have increased the awareness of transplant researchers for alternate therapeutical strategies in this patient cohort.

The survival rates of children with advanced chronic kidney disease (CKD) are significantly lower when compared with general pediatric population. As in adults, cardiovascular disease, infectious risks, uremia-related complications, and metabolic derangements contribute to increased morbidity and mortality. The last 30 years have brought significant advances in our understanding of pediatric chronic kidney disease. However, many approaches to management are still based upon findings described in the adult population. In order to optimize our approach to management and treatment, it is necessary to recognize pediatric CKD as an entity separate from adult CKD in its etiology, pathophysiology, and long-term consequences.

The control of sodium intake, and the implementation of low sodium diet in nephrology clinical practice is very low, is difficult when salt have been implicated as targets for manipulation to limit progression of kidney disease. It is well recognized that better control of blood pressure is important in mitigating the progression of CKD. We describe the effects of Very Low protein Diet on intake of Sodium, and, consequently, on proteinuria and blood pressure.

Despite large sensitization, excess weight, hypertension and cardiovascular risk factors in children and adolescents are extending more and more, as a real new ‘epidemic’. Always more attention has been paid on epidemiology, causes, consequences and factors related to increase blood pressure values among young people. For the first time during 2009, the recommendations of the European Society of Hypertension for the management of high blood pressure in children and adolescents were published, remarking that the most important condition related to paediatric hypertension is the excess weight. The negative metabolic effects of obesity on blood pressure begin early during childhood and track through adolescence into adulthood. Waist circumference and waist-to-height ratio have emerged as better adiposity indicators than body mass index and important predictors of hypertension and cardiovascular risk. Also insulin resistance and high uric acid plasma levels have been advocated as relevant risk factors in children. Moreover a correlation between adipocytokines, in particular leptin and adiponectin, and hypertension and cardiovascular damage in children has been suggested. Obesity-associated hypertension results related to heart damage ( particularly an increase of the left ventricular mass), renal involvement ( presence of microalbuminuria) and autonomic alterations. As first therapy approach in hypertensive children, fundamental is the role of lifestyle measures: reduction of excess weight, increase of physical activity and limitation of sodium in the diet represent the main aspects of this kind of intervention.