SciELO - Scientific Electronic Library Online

 
 Intradialytic resistance training: an effective and easy-to-execute strategyAcute Kidney Injury Epidemiology in pediatrics author indexsubject indexarticles search
Home Pagealphabetic serial listing  

Services on Demand

Journal

Article

Indicators

Related links

Share


Brazilian Journal of Nephrology

Print version ISSN 0101-2800On-line version ISSN 2175-8239

J. Bras. Nefrol., ahead of print  Epub Nov 08, 2018

http://dx.doi.org/10.1590/2175-8239-jbn-2018-0155 

Articles

Hypertension in patients on dialysis: diagnosis, mechanisms, and management

Sérgio Gardano Elias Bucharles1  2 
http://orcid.org/0000-0002-9051-5045

Krissia K.S. Wallbach1 

Thyago Proença de Moraes3 

Roberto Pecoits-Filho3 

1Universidade Federal do Paraná, Hospital de Clínicas, Curitiba, PR, Brasil.

2Fundação Pró Renal, Curitiba, PR, Brasil.

3Pontifícia Universidade Católica do Paraná, Faculdade de Medicina, Curitiba, PR, Brasil.

Abstract

Hypertension (blood pressure > 140/90 mm Hg) is very common in patients undergoing regular dialysis, with a prevalence of 70-80%, and only the minority has adequate blood pressure (BP) control. In contrast to the unclear association of predialytic BP recordings with cardiovascular mortality, prospective studies showed that interdialytic BP, recorded as home BP or by ambulatory blood pressure monitoring in hemodialysis patients, associates more closely with mortality and cardiovascular events. Although BP is measured frequently in the dialysis treatment environment, aspects related to the measurement technique traditionally employed may be unsatisfactory. Several other tools are now available and being used in clinical trials and in clinical practice to evaluate and treat elevated BP in chronic kidney disease (CKD) patients. While we wait for the ongoing review of the CKD Blood Pressure KIDGO guidelines, there is no guideline for the dialysis population addressing this important issue. Thus, the objective of this review is to provide a critical analysis of the information available on the epidemiology, pathogenic mechanisms, and the main pillars involved in the management of blood pressure in stage 5-D CKD, based on current knowledge.

Keywords: Hypertension; Renal Dialysis; Peritoneal Dialysis

Introduction

Understanding the mechanisms, evaluating, and defining the best management of blood pressure (BP) in patients receiving renal replacement therapies through hemodialysis (HD) or peritoneal dialysis (PD), is a significant challenge for healthcare professionals. Although BP is measured frequently in the dialysis treatment environment, aspects related to the measurement technique employed may be unsatisfactory. Several other tools are now available and being used in clinical trials and clinical practice to evaluate and treat elevated BP in chronic kidney disease (CKD) patients.1,2 Different levels of BP may be observed in the same patient under distinct situations, which include evaluations before, during, or after the dialysis session, and at home using ambulatory BP measurements (ABPM), being frequently and substantially lower than during dialysis measurements.3

In patients with end-stage renal disease (ESRD) receiving dialysis, elevated blood pressure is common and poorly controlled in general.4 Although volume overload and sodium retention appear to be the main pathogenic mechanism of hypertension in this population, other factors such as increased arterial stiffness, activation of renin-angiotensin-aldosterone system, sleep apnea, activation of sympathetic nervous system, and use of recombinant erythropoietin may be also involved.5

The association between hypertension and cardiovascular disease risk has been well documented in the general population but in dialysis patients the associated risk is poorly understood, and still present paradoxical and unexpected reports.6 The presence of stage 5-D CKD is associated with a several-fold increased risk of cardiovascular mortality, compared to age- and sex-matched controls without CKD.7 Epidemiological studies have shown that systolic blood pressure (SBP), diastolic blood pressure (DBP) along with traditional risk factors for cardiovascular disease are associated with end-organ damage, including vascular stiffness and poor outcomes in dialysis patients. Indeed, increased and decreased SBP are both associated to cardiovascular disease (CVD) events and decreased SBP following previous hypertension (HTN) is also associated with adverse outcomes.8 While we wait for the ongoing review of the CKD Blood Pressure KIDGO guidelines, so far there is no guideline for the dialysis population addressing this important issue. Thus, the objective of this review is to provide a critical analysis of the information available on the epidemiology, pathogenic mechanisms, and the main pillars involved in the management of blood pressure in stage 5-D CKD, based on current knowledge.

Epidemiology of hypertension in stage 5 CKD dialysis patients

Hypertension (blood pressure > 140/90 mm Hg) is common in patients undergoing regular dialysis, with a prevalence of 70-80% among regular hemodialysis patients9 and only the minority has adequate blood pressure control. The scenario for peritoneal dialysis (PD) patients is not different, and the variability reported for the prevalence of hypertension is even higher ranging from approximately 30 to more than 90%.10 This variability is mostly related to differences in the definitions used to diagnose hypertension and the tools applied in various studies.5 Epidemiological studies in hemodialysis patients in USA, using different ways to define hypertension, revealed that 72 to 88% of all patients studied had elevated BP.4,11,12 However, in those studies, a high proportion of patients with elevated blood pressure was taking antihypertensive agents and the number of patients with controlled BP was low, between 30-50%.4,11

In contrast to the unclear association between predialytic BP recordings and cardiovascular mortality, prospective studies showed that interdialytic BP, recorded as home BP or by ambulatory blood pressure monitoring in hemodialysis patients, has a clearer association with mortality and cardiovascular events.13), (14 In a cross sectional study conducted in Italy with patients on peritoneal dialysis using the WHO/ISH definition, the prevalence of elevated BP was 88%. 15 In other studies, the average 24-hour BP was not different between patients on automated peritoneal dialysis and continuous ambulatory peritoneal dialysis12,16 and there were positive correlations of left ventricular mass index with BP measurements and BP load.16 Elevated blood pressure diagnosed outside the dialysis unit with home or ambulatory BP monitoring is closely related to mortality.3,13 Additionally, dialysis patients often do not have the normal decrease in BP at nighttime,17 increasing their risk for the development of left ventricular hypertrophy and cardiovascular mortality.18 Indeed, Foley et al.19 observed that each 10 mmHg rise in mean BP was independently associated with a progressive increased prevalence of concentric left ventricular hypertrophy, development of "de novo" cardiac failure, and "de novo" ischemic heart disease. Indeed, the degree of cerebral atrophy and predialytic BP as well as cerebral atrophy and duration of hypertension exhibit very high correlation.20 These data suggest that long-term hypertension is frequently, not well controlled, and a significant risk factor for cardiovascular events in CKD hemodialysis patients.

Diagnosis of hypertension in dialysis patients

The diagnosis of hypertension in the general population is based on different available guidelines, such as the American, Brazilian, and European guidelines, increasing the complexity and controversy of the problem.21-23 The National Kidney Foundation - Kidney Diseases Outcomes Quality Initiative guideline established that hypertension in hemodialysis patients is diagnosed when pre-dialysis BP is > 140/90 mmHg or when post-dialysis BP is > 130/80 mmHg,24 but the conventional peridialytic BP recordings may not be accurate. Pre- and post-dialysis BPs measures are obtained by the staff of the dialysis unit, often without the necessary attention to the correct measurement technique.1,2 Additionally, other factors may dictate an inaccurate pre- and post-dialysis BP reading, such as the white-coat effect, fear of incorrect arteriovenous fistula needling, fluctuations in volume status, and limited time for relaxation (patient is anxious to start dialysis).25 Furthermore, the poor diagnostic accuracy of peri-dialytic BP recordings was well stablished by a meta-analysis showing that both pre- and post-dialysis BP readings provide imprecise estimates of the mean interdialytic BP recorded by 44-hour ambulatory BP monitoring.26 Thus, an alternative could be the use of the intradialytic BP measurement average, which may provide greater sensibility and specificity in detecting interdialytic hypertension compared to pre- and post-dialysis BP evaluations.27

However, BP measurements obtained outside dialysis units are frequently needed to diagnose hypertension in dialysis patients. Home BP monitoring is widely applied and strongly recommended for diagnosis and treatment of hypertension in the general population.28 Additionally, home BP was shown to have high short-term reproducibility from one week to the next and it is strongly associated with indices of target organ damage, such as aortic stiffness and left ventricular hypertrophy (LVH).29 Currently, many authors suggest that ambulatory BP monitoring (ABPM) may be the gold standard method for diagnosing hypertension in patients receiving dialysis.2), (12 Observational studies clearly suggest that ABPM predicts all-cause and cardiovascular mortality better than peri-dialytic BP.13 ABPM has the advantage of recording BP at night, because many dialysis patients present a non-dipping nocturnal BP pattern that is associated with LVH and cardiovascular mortality.30 However, ABPM is inconvenient for many dialysis patients with a high treatment burden, high prevalence of sleep disorders and, eventually, compromised bilateral upper limbs with arteriovenous fistula. Therefore, home BP monitoring appears to be a simple and effective approach to evaluate BP and make therapeutic decisions in dialysis patients.31 Table 1 presents information for diagnosis of hypertension in dialysis patients. In contrast to the typical decline in BP during hemodialysis session, 10 to 15% of hemodialysis patients exhibits a paradoxical intradialytic BP elevation32 and although this abnormal response has been long recognized, the exact reason for is still not well known. Intradialytic hypertension may be defined as a rise of at least 15 mmHg in mean BP during dialysis or a rise of at least 10 mmHg in systolic BP during or immediately post-dialysis in a certain number of dialysis sessions (the last three or four dialysis sessions).33

Table 1 Diagnosis of hypertension in dialysis patients 

Hypertension in dialysis patients should be based on home BP or ABPM evaluation.
● Home BP in hemodialysis: an average BP ≥ 135/85 mmHg obtained over 6 non-dialysis days, during a two-week period, with the measurements made in a quiet room, with the patient in seated position, back and arms supported, after 5 minutes of rest and with 2 measurements taken 1-2 minutes apart.
● Home BP in peritoneal dialysis: an average BP ≥ 135/85 mmHg over 7 consecutive days with the above described conditions.
● ABPM in hemodialysis patients: an average BP ≥ 130/80 mmHg over 24-hour monitoring during a mid-week non-dialysis day and, if possible, extended to 44 hours.
● ABPM in peritoneal dialysis: an average BP ≥ 130/80 mmHg over 24-hour monitoring.
● For hemodialysis patients: when neither ABPM nor home BP measurements are available, the diagnosis can be made based on office BP measurements taken in a mid-week non-dialysis day, with the standard technique described above.
● For peritoneal dialysis patients: office BP ≥ 140/90 mmHg obtained with the standard technique as described above.

Adopted from Sarafidis et al.5

Mechanisms involved in blood pressure alterations in stage 5 CKD

The pathophysiology of hypertension in dialysis patients is complex and multifactorial.6,12 A selection of risk factors potentially involved in the development of hypertension in dialysis patients is listed in Figure 1. Increase in cardiac output, peripheral vascular resistance, or both result in BP elevation in dialysis patients. First, excessive intravascular volume is a major pathogenic factor of hypertension in dialysis patients and this extracellular volume expansion is most likely to be observed in hypertensive end-stage renal disease (ESRD) patients.5 Total body water is increased in hypertensive hemodialysis patients when compared to normotensive34 and when excessive body fluids are removed and "dry-weight" is achieved with slow and more frequent dialysis, BP can be ameliorated in approximately 90% of patients.35 Indeed, perturbations in vascular auto-regulation may occur in hypervolemic ESRD patients, namely the inappropriate increase in angiotensin II in relationship to volume, increased vascular reactivity to endogenous pressors, and increased cardiac output in the presence of high peripheral vascular resistance.36 In many cases, hypertension is related to weight gain during the interval between two dialysis sessions and BP may be ameliorated by correcting the extracellular volume, although the results obtained in different studies are contradictory. In fact, a few studies observed that volume status affects interdialytic BP37 while other series failed to confirm this relationship.38 Additionally, there is a correlation between loss of weight during hemodialysis and lowering SBP, 39 and volume sensitivity is higher in hypertensive compared to normotensive dialysis patients.40

Figure 1 Factors involved in the development of hypertension in dialysis patients. 

The normalization of the patient's extra-cellular volume is also reported to improve the circadian BP rhythm, which may be abnormal in the presence of volume expansion.41 In patients who remain hypertensive despite intensive ultrafiltration, sodium and volume excess may play only a secondary role. Additionally, the lack of correlation between extracellular volume and BP in these patients has been previously described.42 Interestingly, Titze et al.43 recently described an unknown sodium storage system particularly bound to glycosaminoglycans in skin that does not promote osmotic activity. This novel compartment, at sodium concentrations of 180-190 meq/L, acts as a buffer to exogenous sodium. Inappropriately, this sodium store could be released into the blood, resulting in hypervolemia and oxidative stress or inducing the activation of cellular mechanisms involved in tissue fibrosis. Indeed, in hemodialysis patients, sodium and water in skin and muscle are increased and vascular endothelial growth factor (VEGF) is reduced when compared to age-matched healthy individuals, and this phenomenon may contribute to hypertension.44

The role of excessive renin secretion in relation to volume status and sodium has been recognized as an important factor in the pathogenesis of hypertension in dialysis patients. It is well-known that activation of the renin-angiotensin-aldosterone system occurs even in ESRD patients in dialysis treatment,45 eventually resulting in dialysis refractory renin-dependent hypertension. Additionally, secondary hyperaldosteronism contributes to hypertension and it has recently become clear that apart from hypertension, aldosterone may have numerous blood-pressure-independent actions that under conditions of high salt concentration, is injurious to the kidney, heart, and vasculature.46

Increase arterial stiffness occurs frequently in dialysis patients, mainly related to calcium and phosphate disturbance metabolism resulting in vascular calcification.47 Premature vascular aging and arterial stiffening are observed with progression of CKD and in ESRD. This accelerated aging is associated with outward remodeling of large vessels, characterized by increased arterial radius that is not totally compensated for by artery wall hypertrophy. Arterial stiffening in CKD and ESRD patients is of multifactorial origin with extensive arterial calcifications representing a major covariate.48 In dialysis patients, arterial stiffness assessed by aortic pulse wave velocity (PWV) is closely related to high interdialytic BP, and increasing PWV blunts the circadian amplitude of systolic BP and pulse pressure.49

Increased activity of the sympathetic nervous system may contribute to hypertension in ESRD patients.50 Sympathetic nerve discharge was 2.5 times higher in dialysis patients than in normal subjects and this discharge was not correlated with either plasma noradrenaline concentration or plasma renin activity.51 Fluid overload of greater than 6% of body weight results in activation of the sympathetic nervous system,52 and angiotensin-converting enzyme (ACE) inhibition could result in reduction of this sympathetic hyperactivity.53 Endothelium-dependent vasodilatation is impaired in uremia, and nitric oxide (NO) deficiency occurs in ESRD patients, contributing to hypertension in hemodialysis and peritoneal dialysis patients.54 The production of NO by the vascular endothelium is inhibited by asymmetric dimethylarginine (ADMA), which accumulates in CKD patients, particularly in those with atherosclerotic complications.55 However, no significant correlation was observed between ADMA concentrations and BP in dialysis patients.34 Additionally, deficiency of renalase, an enzyme produced by the kidney that metabolizes catecholamines and catecholamines-like substances, may contribute to increased sympathetic nervous system activity in CKD.56

Endothelial dysfunction may contribute to hypertension in dialysis patients through several mechanisms. Patients with CKD show reduced NO availability measured as NO-dependent vasodilatation and this phenomenon may be related to reduced NO production.57 Indeed, high circulating levels of asymmetric dimethylarginine (ADMA), an endogenous NO synthase inhibitor, are observed in CKD patients, 58 and in ESRD hemodialysis patients, ADMA is associated with cardiovascular disease and mortality. 59 Additionally, endothelin-1 may have an important role in the development of intradialytic hypertension, 60 which occurs regularly in 10-15% of hemodialysis patients.61

In 20 to 30% of CKD patients, regular administration of human recombinant erythropoietin (rHuEPO) is accompanied by "de novo" hypertension or aggravation of preexisting hypertension, and the increase in BP occurs within a few weeks to months after initiation of rHuEPO.62 Grekas et al.40 observed hypertension in 62% of rHuEPO-treated hemodialysis patients but only in 38% of those not receiving rHuEPO. An increase in red cell mass during or after correction of anemia leads to increase whole-blood viscosity and cardiac afterload63 and may contribute to hypertension in those patients, but increase in BP may occur even before hematocrit increases.64 Other factors related to rHuEPO-induced hypertension in CKD patients include endothelin release, vascular endothelial dysfunction, preexisting hypertension, elevation of cytosolic free calcium in vascular smooth muscle cells, inhibition of NO synthesis, and rapid correction of anemia.65 Additionally, higher rHuEPO doses, higher target hemoglobin levels,66 and possibly dialysis modality67 have been associated with a higher BP response.

Sleep apnea is highly prevalent and may be related to volume overload68 in dialysis patients. Nocturnal hypoxemia in sleep apnea has been associated with higher nocturnal SBP and left ventricular relative wall thickness,30 and resistant hypertension,12,69 while the obstructive apnea-hypopnea index is significantly reduced after hemodialysis with reduction of fluid overload.70

Secondary hyperparathyroidism may also result in hypertension in ESRD population by mechanisms including entry of calcium into vessel wall smooth muscle cells. However, parathyroidectomy failed to correct hypertension in patients on chronic hemodialysis.71 In contrast, activated vitamin D therapy for secondary hyperparathyroidism resulted in significant decreases in mean BP.72

In dialysis patients, plasma α-human atrial natriuretic peptide (α-ANP) levels are elevated, reflecting extracellular volume expansion. The α-ANP values decrease post-dialysis but remain elevated in patients with altered left atrial hemodynamics (65). Similar to α-ANP, the concentration of brain natriuretic peptide (BNP) is higher in hemodialysis patients than in healthy volunteers, and BNP is lowered less efficiently by dialysis procedure.73 Franz et al.74 observed that, in hemodialysis patients with moderate or severe hypertension, the levels of pro-ANP fragments and α-ANP were higher than in patients with mild hypertension. Indeed, cardiac natriuretic peptides are related to left ventricular mass and predict cardiovascular mortality in dialysis patients.6

Although it has been established that interdialytic salt restriction or intradialytic removal of salt and fluids is effective in reducing BP, success over time is very rare.75 Other studies have been performed in dialysis population to investigate the impact of salt restriction on blood pressure levels. Ozkahya et al.,76 by emphasizing sodium restriction, stopping all antihypertensive drugs, and intensifying ultrafiltration, observed not only significant reduction on BP levels, but also in left ventricle wall thickness. The same group observed, in another study, that sodium chloride restriction to < 6 g/day determined normalization of BP levels after 36 months.77

Because the sodium concentrate of the dialysate is usually higher than that of the patient's serum, it can influence post dialysis thirst, interdialytic weight gain, and BP. In addition, salt balance is positive with the habitual high dietary sodium intake and use of saline solutions to maintain plasma volume during UF and to treat hypotension episodes during dialysis treatment. Low sodium level in dialysate resulted in lower intra- and inter-dialytic plasma sodium when compared with high dialysate sodium,78 and a programmed variable sodium dialysis from 155 meq/L to 135mEq/L resulted in a reduction of antihypertensive drugs use, without alterations in predialytic BP when compared to a dialysate sodium concentration of 140 meq/L.79

Management of hypertension in stage 5 CKD

Current data from several observational studies12,80 and a prospective cohort study81 suggest a "U-shaped" association between pre-HD BP and mortality. This means that blood pressure below certain levels may be more harmful than high levels, especially when patients present with severe cardiomyopathy, that often modifies the relationship between BP and mortality, determining a very low survival in ESRD patients with SBP < 115 mmHg (82). On the other hand, post-dialysis SBP > 180 and DBP > 90 mmHg were associated with increase in cardiovascular mortality and should be treated aggressively.83 This reverse epidemiology of BP and cardiovascular mortality makes it difficult to establish a real and reliable target for BP levels in dialysis patients. Nevertheless, international guidelines for cardiovascular disease recommend BP level less than 140/90 mmHg at the beginning of the week. However, this recommendation should not be applied uniformly in the dialysis setting,12,84 because the aggressive approach to control BP can increase the risk of symptomatic intra-dialytic hypotension and its consequences.

Non-pharmacological therapy

Most patients in stage 5 CKD develop a positive sodium balance and an increase in extracellular volume (ECV), with salt and water overload playing a central role in the development of hypertension. High salt intake has been shown to be associated with high pre-dialysis SBP and cardiovascular disease.85 Normalizing sodium and fluids balance is key to control BP and to reduce cardiovascular events, as stated by the most recent guideline;6 dietary salt restriction should be below 5-6 g/day and interdialytic weight gain should not exceed 0.8 kg/day. Indeed, in peritoneal dialysis patients, salt and water excess are the most important determinants of elevated BP12,86 and many authors recommend salt restriction (< 5g/day) for all peritoneal dialysis patients unless there is evidence of volume contraction.87 Such dietary targets are particularly important in the presence of loss of residual renal function and when the patient have a high membrane transport that negatively interfere in the ultrafiltration.

Another way to regulate the fluid volume of dialysis patients, particularly in hemodialysis, is to set an appropriate dry weight (DW). In clinical practice, the DW is usually established by a progressive decline in post dialysis body weight over a 4-8-week period after initiation of maintenance hemodialysis (88). This post-dialysis DW may be defined as the post dialysis body weight at which ECV in within the normal range or the target BP value without the need for antihypertensive medications.6 These definitions, obviously, cannot be applied to those patients who are hypotensive because of cardiomyopathy. In contrast, establishing a DW for PD patients is very complicated and the motive of frequent debates. There are some attempts to monitor volume status of PD patients with multifrequency bioimpedance and the results are acceptable.12,89

The clinical history and physical examination may help in detecting more obvious ECV increases, but in general, assessment of DW using clinical parameters presents low sensitivity.90 Attempts have been made to determine DW by bioimpedance device (BIA)91 by monitoring regional resistance and resistivity in the calf, showing that the prescribed target weight can be decrease over time, improving BP control. Other BIA devices that assess whole body composition provide readouts of BP and ECV status that may be helpful in the follow-up of fluid balance and information about increased risk of mortality when overhydration is present.92 Randomized control studies have demonstrated that optimization of DW by bioimpedance methods are safe and capable of improving BP control in dialysis patients.12,93

Other methods for assessing ECV include measurement of vena cava diameter, which requires time for post dialysis equilibration and is operator-dependent.94 Lung ultrasound can detect asymptomatic pulmonary congestion in hemodialysis patients, and the resulting BL-US (B-lines ultrasound) score is a strong and independent predictor of death and cardiac events in this population.

Increasing the dialysate sodium concentration above the pre-dialysis values may help reduce episodes of intradialytic hypotension but may lead to increased weight gain by enhanced thirst.6 It may be best to adjust sodium dialysate concentration to match the patient's pre-dialysis plasma sodium and not use higher dialysate sodium. Use of hypertonic dextrose rather than saline in the management of intradialytic hypotension and cramps also increases the potential for a neutral sodium balance. Dietary salt restriction is useful for DW optimization and blood pressure control in dialysis patients. Several studies have consistently reported a decrease in interdialytic weight gain, associated reduction in BP levels, and more significant reduction in left ventricular mass.12,96

More frequent dialysis sessions

Conventional hemodialysis is frequently associated with high ultrafiltration (UF) rates, which enhance the risk of muscle cramps and hypotensive episodes. The symptoms are treated by saline intravenous infusion, which favors an expanded ECV, hypertension, and risk of developing LVH. The prescription of longer or more frequent dialysis sessions allows the decrease in UF rates and reduces the risk of intradialytic complications,97 improving LVH98 and cardiac function.99 More frequent hemodialysis sessions than the conventional three times weekly regimen reduces BP more consistently and requires fewer anti-hypertensive medications to achieve the same BP control.12,100 The European Best Practice guidelines recommend that the length of the hemodialysis session should not be determined only by an optimal KT/V result, but by stablishing at least three dialysis sessions of 4 hours each to ensure optimal volume status.101

Additionally, in the FREEDOM trial,102 a prospective cohort study of short daily HD, the mean number of prescribed antihypertensive agents decreased from 1.7 to 1.0 in 1 year, whereas the percentage of patients not prescribed antihypertensive agents increased from 21 to 47%. Kotanko et al.103 analyzed the effects of more frequent hemodialysis sessions on BP control in a randomized controlled trial, including patients on daily diurnal and nocturnal HD treatment versus conventional three weekly HD sessions and observed after twelve months a sustained and significant reduction in both diastolic and systolic BP, as well in the number of prescribe antihypertensive medications. Nocturnal HD appears to markedly reduce total peripheral resistance and plasma norepinephrine and restore endothelium-dependent vasodilation. In conclusion, the above information indicate that intensive HD, in general, reduces BP and the need for antihypertensive medications.

Pharmacological therapy

When prescribing antihypertensive drugs to stage 5 CKD patients on dialysis one must be aware that pharmacokinetics may be altered by the impaired kidney excretion and the drug dialyzability. In addition, reduced compliance, side effects, and financial costs can have an impact in treatment effectiveness. Other problems related to this special population are the occurrence of intradialytic hypotension and vascular access thrombosis.104 Moreover, some antihypertensive effects drugs are also cardioprotective, decreasing the risk of death by cardiovascular disease. Examples of drugs in this category are the renin-angiotensin-aldosterone system (RAAS) inhibitors, β-adrenergic blockers, calcium channel blockers (CCBs), and aldosterone inhibitors (for patients not on dialysis). Angiotensin II has been implicated in endothelial dysfunction, smooth muscle proliferation, atherosclerotic plaque rupture, and LVH, the latter occurring even when BP is controlled.6 In the general population, the use of RAAS decreases cardiovascular events105 in patients with left ventricular dysfunction and in stable coronary artery disease. Similarly, in the non-ESRD population, the clinical use of β-blockers confer cardiovascular protection106 and CCBs decrease intracellular calcium levels produced by secondary hyperparathyroidism and alter lipid profile, which may reduce cardiovascular risk107.

Studies of antihypertensive drugs in CKD dialysis patients have shown limited results and two meta-analysis of randomized trials conclude that the real merit of these drugs (RAAS, CCBs, β-adrenergic blockers) are not well established.108,109 The two meta-analyses confirmed that treatment with antihypertensive agents was associated with reduction on cardiovascular events, but when normotensive patients were included in the analysis, the beneficial effects of the drugs were markedly diminished, becoming non-significant. Most importantly, none of the trials included in these meta-analyses specifically targeted BP levels. According to these data, BP control by anti-hypertensive drugs leads to better cardiovascular outcomes, however, an optimal regimen to control BP and reduce mortality has not yet been stablished.

As for hemodialysis, there is a lack of studies to define the ideal target for blood pressure to reduce cardiovascular events. However, one recent study deserves some comments. A randomized controlled trial described a significant benefit in the cardiac function of peritoneal dialysis patients with the use spironolactone in addition to a RAAS inhibitor without any additional risk of hyperkalemia.110 Finally, there are not enough studies comparing the benefits of one class of antihypertensive over another for PD patients. Nevertheless, the positive impact of the RAAS inhibitors on the residual renal function and in the preservation of the peritoneal membrane found in some studies gave some popularity to these classes of antihypertensive drugs.111,112

Recommendations on antihypertensive drugs in CKD dialysis patients are based on their effects in BP reduction, side effects, and protective cardiovascular effects. The use of RAAS inhibitors, β-adrenergic blockers, and CCBs is desirable in dialysis patients because of their effects on plasma renin activity, in reducing sympathetic activity, and in decreasing intracellular calcium levels, respectively.6 Beyond any individual preference, there is no strong evidence to recommend one specific class of antihypertensive drug over another in CKD dialysis population and only few clinical trials have demonstrated some beneficial cardiovascular effects of RAAS inhibition and β-adrenergic blockers in those patients.113,114 RAAS inhibitors should be used in CKD-VD patients because these agents are particularly beneficial for cardiac disease frequently observed in dialysis patients and are effective in reducing left ventricular mass and mortality.115,116 Specifically related to this topic of interest, there is an ongoing phase 3 trial evaluating Spironolactone 25 mg (Aldosterone bloCkade for Health Improvement EValuation in End-stage Renal Disease (ACHIEVE) - https://clinicaltrials.gov/ct2/show/NCT03020303) and its purpose is to determine if spironolactone reduces death or hospitalization for heart failure and if the drug is well tolerated in patients that require dialysis.

Hypertension and heart failure (HF) are conditions frequently seen in the CKD population and sympathetic overactivity plays an important role in this scenario, making β-blockers suitable for treating both conditions (117). A meta-analysis concluded that treatment with β-blockers improved all-cause mortality in patients with CKD and heart failure (118). Additionally, some prospective studies demonstrated that the use of β-blockers are associated with reduce risk of mortality in hemodialysis patients.114,119 More recent, another therapeutic agent, sacubitril-valsartan, was approved for use in patients with HF and this dual-acting agent enhances the functions of natriuretic peptides and inhibits the renin-angiotensin system,120 with potential benefit for CKD patients.

Finally, the removal of an antihypertensive drug during dialysis sessions (for example β-blockers) may predispose patients to uncontrolled BP121 and the pharmacokinetic of ACE inhibitors are quite different among each other, determining the post-dialysis supplementation of drugs in some cases. Some drugs with long-acting antihypertensive effects (Atenolol and Lisinopril) can be administered thrice weekly, thus enhancing pharmaco-adherence.12,122

Conclusions

Hypertension is frequently diagnosed in the dialysis population, difficult to manage, and associated with an increased risk of cardiovascular disease. The complex pathophysiology of this condition explains the great difficulty of its treatment. At present, the superiority of home self-measured blood pressure over pre-hemodialysis is convincing and other investigation tools, like ambulatory blood pressure monitoring, are becoming more applied in CKD populations. In general, all antihypertensive drugs can be used in dialysis population, with the adequate dose adjustment determined by clearance during dialysis sessions. The use of combined non-pharmacologic, particularly dietary sodium restriction, dialysate sodium adjustment and use of antihypertensive drugs (preferentially cardioprotective ones) may be the best practice to optimize blood pressure control. Randomized clinical trials with anti-hypertensive drugs aiming to reduce mortality are still needed, as well as a definitive guideline of BP control in dialysis population. In addition, non-pharmacological interventions with different dialysis modalities or schemes and sodium restriction should be adequately tested in this high-risk population.

References

1 Parati G, Ochoa JE, Bilo G, Agarwal R, Covic A, Dekker FW, et al.; European Renal and Cardiovascular Medicine (EURECA-m) working group of the European Renal Association-European Dialysis Transplantation Association (ERA-EDTA). Hypertension in Chronic Kidney Disease Part 2: Role of Ambulatory and Home Blood Pressure Monitoring for Assessing Alterations in Blood Pressure Variability and Blood Pressure Profiles. Hypertension 2016;67:1102-10. [ Links ]

2 Parati G, Ochoa JE, Bilo G, Agarwal R, Covic A, Dekker FW, et al.; European Renal and Cardiovascular Medicine (EURECA-m) working group of the European Renal Association-European Dialysis Transplantation Association (ERA-EDTA). Hypertension in Chronic Kidney Disease Part 1: Out-of-Office Blood Pressure Monitoring: Methods, Thresholds, and Patterns. Hypertension 2016;67:1093-101. [ Links ]

3 Alborzi P, Patel N, Agarwal R. Home blood pressures are of greater prognostic value than hemodialysis unit recordings. Clin J Am Soc Nephrol 2007;2:1228-34. [ Links ]

4 Agarwal R, Nissenson AR, Batlle D, Coyne DW, Trout JR, Warnock DG. Prevalence, treatment, and control of hypertension in chronic hemodialysis patients in the United States. Am J Med 2003;115:291-7. [ Links ]

5 Sarafidis PA, Persu A, Agarwal R, Burnier M, de Leeuw P, Ferro CJ, et al. Hypertension in dialysis patients: a consensus document by the European Renal and Cardiovascular Medicine (EURECA-m) working group of the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) and the Hypertension and the Kidney working group of the European Society of Hypertension (ESH). Nephrol Dial Transplant 2017;32:620-40. [ Links ]

6 Levin NW, Kotanko P, Eckardt KU, Kasiske BL, Chazot C, Cheung AK, et al. Blood pressure in chronic kidney disease stage 5D-report from a Kidney Disease: Improving Global Outcomes controversies conference. Kidney Int 2010;77:273-84. [ Links ]

7 Foley RN, Collins AJ. End-stage renal disease in the United States: an update from the United States Renal Data System. J Am Soc Nephrol 2007;18:2644-8. [ Links ]

8 Li Z, Lacson E Jr, Lowrie EG, Ofsthun NJ, Kuhlmann MK, Lazarus JM, et al. The epidemiology of systolic blood pressure and death risk in hemodialysis patients. Am J Kidney Dis 2006;48:606-15. [ Links ]

9 Cheigh JS, Milite C, Sullivan JF, Rubin AL, Stenzel KH. Hypertension is not adequately controlled in hemodialysis patients. Am J Kidney Dis 1992;19:453-9. [ Links ]

10 Ortega LM, Materson BJ. Hypertension in peritoneal dialysis patients: epidemiology, pathogenesis, and treatment. J Am Soc Hypertens 2011;5:128-36. [ Links ]

11 Salem MM. Hypertension in the hemodialysis population: a survey of 649 patients. Am J Kidney Dis 1995;26(3):461-8. [ Links ]

12 Agarwal R. Supervised atenolol therapy in the management of hemodialysis hypertension. Kidney Int 1999;55:1528-35. [ Links ]

13 Amar J, Vernier I, Rossignol E, Bongard V, Arnaud C, Conte JJ, et al. Nocturnal blood pressure and 24-hour pulse pressure are potent indicators of mortality in hemodialysis patients. Kidney Int 2000;57:2485-91. [ Links ]

14 Tripepi G, Fagugli RM, Dattolo P, Parlongo G, Mallamaci F, Buoncristiani U, et al. Prognostic value of 24-hour ambulatory blood pressure monitoring and of night/day ratio in nondiabetic, cardiovascular events-free hemodialysis patients. Kidney Int 2005;68:1294-302. [ Links ]

15 Cocchi R, Degli Esposti E, Fabbri A, Lucatello A, Sturani A, Quarello F, et al. Prevalence of hypertension in patients on peritoneal dialysis: results of an Italian multicentre study. Nephrol Dial Transplant 1999;14:1536-40. [ Links ]

16 Atas N, Erten Y, Okyay GU, Inal S, Topal S, Öneç K, et al. Left ventricular hypertrophy and blood pressure control in automated and continuous ambulatory peritoneal dialysis patients. Ther Apher Dial 2014;18:297-304. [ Links ]

17 Baumgart P, Walger P, Gemen S, von Eiff M, Raidt H, Rahn KH. Blood pressure elevation during the night in chronic renal failure, hemodialysis and after renal transplantation. Nephron 1991;57:293-8. [ Links ]

18 Foley RN, Parfrey PS, Harnett JD, Kent GM, Martin CJ, Murray DC, et al. Clinical and echocardiographic disease in patients starting end-stage renal disease therapy. Kidney Int 1995;47:186-92. [ Links ]

19 Foley RN, Parfrey PS, Harnett JD, Kent GM, Murray DC, Barre PE. Impact of hypertension on cardiomyopathy, morbidity and mortality in end-stage renal disease. Kidney Int 1996;49:1379-85. [ Links ]

20 Savazzi GM, Cusmano F, Bergamaschi E, Vinci S, Allegri L, Garini G. Hypertension as an etiopathological factor in the development of cerebral atrophy in hemodialyzed patients. Nephron 1999;81:17-24. [ Links ]

21 Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison Himmelfarb C, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2018;71:e127-248. [ Links ]

22 Mancia G, Fagard R, Narkiewicz K, Redón J, Zanchetti A, Böhm M, et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens 2013;31:1281-357. [ Links ]

23 Malachias MVB, Gomes MAM, Nobre F, Alessi A, Feitosa AD, Coelho EB. 7th Brazilian Guideline of Arterial Hypertension: Chapter 2 - Diagnosis and Classification. Arq Bras Cardiol 2016;107:7-13. [ Links ]

24 Kidney Disease Outcomes Quality Initiative (K/DOQI). K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kidney Dis 2004;43:S1-290. [ Links ]

25 Rohrscheib MR, Myers OB, Servilla KS, Adams CD, Miskulin D, Bedrick EJ, et al. Age-related blood pressure patterns and blood pressure variability among hemodialysis patients. Clin J Am Soc Nephrol 2008;3:1407-14. [ Links ]

26 Agarwal R, Peixoto AJ, Santos SF, Zoccali C. Pre- and postdialysis blood pressures are imprecise estimates of interdialytic ambulatory blood pressure. Clin J Am Soc Nephrol 2006;1:389-98. [ Links ]

27 Agarwal R, Metiku T, Tegegne GG, Light RP, Bunaye Z, Bekele DM, et al. Diagnosing hypertension by intradialytic blood pressure recordings. Clin J Am Soc Nephrol 2008;3:1364-72. [ Links ]

28 Parati G, Stergiou GS, Asmar R, Bilo G, de Leeuw P, Imai Y, et al.; ESH Working Group on Blood Pressure Monitoring. European Society of Hypertension guidelines for blood pressure monitoring at home: a summary report of the Second International Consensus Conference on Home Blood Pressure Monitoring. J Hypertens 2008;26:1505-26. [ Links ]

29 Moriya H, Ohtake T, Kobayashi S. Aortic stiffness, left ventricular hypertrophy and weekly averaged blood pressure (WAB) in patients on haemodialysis. Nephrol Dial Transplant 2007;22:1198-204. [ Links ]

30 Zoccali C, Benedetto FA, Tripepi G, Cambareri F, Panuccio V, Candela V, et al. Nocturnal hypoxemia, night-day arterial pressure changes and left ventricular geometry in dialysis patients. Kidney Int 1998;53:1078-84. [ Links ]

31 Zoccali C, Tripepi R, Torino C, Tripepi G, Mallamaci F. Moderator's view: Ambulatory blood pressure monitoring and home blood pressure for the prognosis, diagnosis and treatment of hypertension in dialysis patients. Nephrol Dial Transplant 2015;30:1443-8. [ Links ]

32 Georgianos PI, Sarafidis PA, Zoccali C. Intradialysis Hypertension in End-Stage Renal Disease Patients: Clinical Epidemiology, Pathogenesis, and Treatment. Hypertension 2015;66:456-63. [ Links ]

33 Inrig JK. Intradialytic hypertension: a less-recognized cardiovascular complication of hemodialysis. Am J Kidney Dis 2010;55:580-9. [ Links ]

34 Anderstam B, Katzarski K, Bergström J. Serum levels of NG, NG-dimethyl-L-arginine, a potential endogenous nitric oxide inhibitor in dialysis patients. J Am Soc Nephrol 1997;8:1437-42. [ Links ]

35 Chazot C, Charra B, Laurent G, Didier C, Vo Van C, Terrat JC, et al. Interdialysis blood pressure control by long haemodialysis sessions. Nephrol Dial Transplant 1995;10:831-7. [ Links ]

36 Mailloux LU. Hypertension in chronic renal failure and ESRD: prevalence, pathophysiology, and outcomes. Semin Nephrol 2001;21:146-56. [ Links ]

37 Rahman M, Dixit A, Donley V, Gupta S, Hanslik T, Lacson E, et al. Factors associated with inadequate blood pressure control in hypertensive hemodialysis patients. Am J Kidney Dis 1999;33:498-506. [ Links ]

38 Savage T, Fabbian F, Giles M, Tomson CR, Raine AE. Interdialytic weight gain and 48-h blood pressure in haemodialysis patients. Nephrol Dial Transplant 1997;12:2308-11. [ Links ]

39 Mittal SK, Kowalski E, Trenkle J, McDonough B, Halinski D, Devlin K, et al. Prevalence of hypertension in a hemodialysis population. Clin Nephrol 1999;51:77-82. [ Links ]

40 Grekas D, Bamichas G, Bacharaki D, Goutzaridis N, Kasimatis E, Tourkantonis A. Hypertension in chronic hemodialysis patients: current view on pathophysiology and treatment. Clin Nephrol 2000;53:164-8. [ Links ]

41 Zucchelli P, Santoro A. Dry weight in hemodialysis: volemic control. Semin Nephrol 2001;21:286-90. [ Links ]

42 Schultze G, Piefke S, Molzahn M. Blood pressure in terminal renal failure. Fluid spaces and the renin-angiotensin-system. Nephron 1980;25:15-24. [ Links ]

43 Titze J, Ritz E. Salt and its effect on blood pressure and target organ damage: new pieces in an old puzzle. J Nephrol 2009;22:177-89. [ Links ]

44 Dahlmann A, Dörfelt K, Eicher F, Linz P, Kopp C, Mössinger I, et al. Magnetic resonance-determined sodium removal from tissue stores in hemodialysis patients. Kidney Int 2015;87:434-41. [ Links ]

45 Kornerup HJ, Schmitz O, Danielsen H, Pedersen EB, Giese J. Significance of the renin-angiotensin system for blood pressure regulation in end-stage renal disease. Contrib Nephrol 1984;41:123-7. [ Links ]

46 Ritz E, Koleganova N. Aldosterone in uremia - beyond blood pressure. Blood Purif 2010;29:111-3. [ Links ]

47 Georgianos PI, Sarafidis PA, Lasaridis AN. Arterial stiffness: a novel cardiovascular risk factor in kidney disease patients. Curr Vasc Pharmacol 2015;13:229-38. [ Links ]

48 Briet M, Boutouyrie P, Laurent S, London GM. Arterial stiffness and pulse pressure in CKD and ESRD. Kidney Int 2012;82:388-400. [ Links ]

49 Agarwal R, Light RP. Arterial stiffness and interdialytic weight gain influence ambulatory blood pressure patterns in hemodialysis patients. Am J Physiol Renal Physiol 2008;294:F303-8. [ Links ]

50 Campese VM, Romoff MS, Levitan D, Lane K, Massry SG. Mechanisms of autonomic nervous system dysfunction in uremia. Kidney Int 1981;20:246-53. [ Links ]

51 Converse RL Jr, Jacobsen TN, Toto RD, Jost CM, Cosentino F, Fouad-Tarazi F, et al. Sympathetic overactivity in patients with chronic renal failure. N Engl J Med 1992;327:1912-8. [ Links ]

52 Odar-Cederlöf I, Ericsson F, Theodorsson E, Kjellstrand CM. Is neuropeptide Y a contributor to volume-induced hypertension? Am J Kidney Dis 1998;31:803-8. [ Links ]

53 Ligtenberg G, Blankestijn PJ, Oey PL, Klein IH, Dijkhorst-Oei LT, Boomsma F, et al. Reduction of sympathetic hyperactivity by enalapril in patients with chronic renal failure. N Engl J Med 1999;340:1321-8. [ Links ]

54 Schmidt RJ, Domico J, Samsell LS, Yokota S, Tracy TS, Sorkin MI, et al. Indices of activity of the nitric oxide system in hemodialysis patients. Am J Kidney Dis 1999;34:228-34. [ Links ]

55 Kielstein JT, Böger RH, Bode-Böger SM, Schäffer J, Barbey M, Koch KM, et al. Asymmetric dimethylarginine plasma concentrations differ in patients with end-stage renal disease: relationship to treatment method and atherosclerotic disease. J Am Soc Nephrol 1999;10:594-600. [ Links ]

56 Desir GV. Regulation of blood pressure and cardiovascular function by renalase. Kidney Int 2009;76:366-70. [ Links ]

57 Wever R, Boer P, Hijmering M, Stroes E, Verhaar M, Kastelein J, et al. Nitric oxide production is reduced in patients with chronic renal failure. Arterioscler Thromb Vasc Biol 1999;19:1168-72. [ Links ]

58 Vallance P, Leone A, Calver A, Collier J, Moncada S. Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure. Lancet 1992;339:572-5. [ Links ]

59 Boger RH, Zoccali C. ADMA: a novel risk factor that explains excess cardiovascular event rate in patients with end-stage renal disease. Atheroscler Suppl 2003;4:23-8. [ Links ]

60 Gutiérrez-Adrianzén OA, Moraes ME, Almeida AP, Lima JW, Marinho MF, Marques AL, et al. Pathophysiological, cardiovascular and neuroendocrine changes in hypertensive patients during the hemodialysis session. J Hum Hypertens 2015;29:366-72. [ Links ]

61 Van Buren PN. Pathophysiology and implications of intradialytic hypertension. Curr Opin Nephrol Hypertens 2017;26:303-10. [ Links ]

62 Abraham PA, Macres MG. Blood pressure in hemodialysis patients during amelioration of anemia with erythropoietin. J Am Soc Nephrol 1991;2:927-36. [ Links ]

63 Mayer G, Hörl WH. Cardiovascular effects of increasing hemoglobin in chronic renal failure. Am J Nephrol 1996;16:263-7. [ Links ]

64 Lebel M, Kingma I, Grose JH, Langlois S. Hemodynamic and hormonal changes during erythropoietin therapy in hemodialysis patients. J Am Soc Nephrol 1998;9:97-104. [ Links ]

65 Hörl MP, Hörl WH. Hemodialysis-associated hypertension: pathophysiology and therapy. Am J Kidney Dis 2002;39:227-44. [ Links ]

66 Phrommintikul A, Haas SJ, Elsik M, Krum H. Mortality and target haemoglobin concentrations in anaemic patients with chronic kidney disease treated with erythropoietin: a meta-analysis. Lancet 2007;369:381-8. [ Links ]

67 Krapf R, Hulter HN. Arterial hypertension induced by erythropoietin and erythropoiesis-stimulating agents (ESA). Clin J Am Soc Nephrol 2009;4:470-80. [ Links ]

68 Tada T, Kusano KF, Ogawa A, Iwasaki J, Sakuragi S, Kusano I, et al. The predictors of central and obstructive sleep apnoea in haemodialysis patients. Nephrol Dial Transplant 2007;22:1190-7. [ Links ]

69 Abdel-Kader K, Dohar S, Shah N, Jhamb M, Reis SE, Strollo P, et al. Resistant hypertension and obstructive sleep apnea in the setting of kidney disease. J Hypertens 2012;30:960-6. [ Links ]

70 Ogna A, Forni Ogna V, Mihalache A, Pruijm M, Halabi G, Phan O, et al. Obstructive Sleep Apnea Severity and Overnight Body Fluid Shift before and after Hemodialysis. Clin J Am Soc Nephrol 2015;10:1002-10. [ Links ]

71 Ifudu O, Matthew JJ, Macey LJ, Hong JS, Sumrani N, Sommer BG, et al. Parathyroidectomy does not correct hypertension in patients on maintenance hemodialysis. Am J Nephrol 1998;18:28-34. [ Links ]

72 Raine AE, Bedford L, Simpson AW, Ashley CC, Brown R, Woodhead JS, et al. Hyperparathyroidism, platelet intracellular free calcium and hypertension in chronic renal failure. Kidney Int 1993;43:700-5. [ Links ]

73 Kohse KP, Feifel K, Mayer-Wehrstein R. Differential regulation of brain and atrial natriuretic peptides in hemodialysis patients. Clin Nephrol 1993;40:83-90. [ Links ]

74 Franz M, Woloszczuk W, Hörl WH. N-terminal fragments of the proatrial natriuretic peptide in patients before and after hemodialysis treatment. Kidney Int 2000;58:374-83. [ Links ]

75 Luik AJ, v d Sande FM, Weideman P, Cheriex E, Kooman JP, Leunissen KM. The influence of increasing dialysis treatment time and reducing dry weight on blood pressure control in hemodialysis patients: a prospective study. Am J Nephrol 2001;21:471-8. [ Links ]

76 Ozkahya M, Ok E, Cirit M, Aydin S, Akçiçek F, Basçi A, et al. Regression of left ventricular hypertrophy in haemodialysis patients by ultrafiltration and reduced salt intake without antihypertensive drugs. Nephrol Dial Transplant 1998;13:1489-93. [ Links ]

77 Ozkahya M, Töz H, Unsal A, Ozerkan F, Asci G, Gürgün C, et al. Treatment of hypertension in dialysis patients by ultrafiltration: role of cardiac dilatation and time factor. Am J Kidney Dis 1999;34:218-21. [ Links ]

78 De Nicola L, Bellizzi V, Minutolo R, Cioffi M, Giannattasio P, Terracciano V, et al. Effect of dialysate sodium concentration on interdialytic increase of potassium. J Am Soc Nephrol 2000;11:2337-43. [ Links ]

79 Flanigan MJ, Khairullah QT, Lim VS. Dialysate sodium delivery can alter chronic blood pressure management. Am J Kidney Dis 1997;29:383-91. [ Links ]

80 Carney EF. Dialysis: U-shaped associations between changes in blood pressure during dialysis and patient survival. Nat Rev Nephrol 2013;9:431. [ Links ]

81 Robinson BM, Tong L, Zhang J, Wolfe RA, Goodkin DA, Greenwood RN, et al. Blood pressure levels and mortality risk among hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study. Kidney Int 2012;82:570-80. [ Links ]

82 Klassen PS, Lowrie EG, Reddan DN, DeLong ER, Coladonato JA, Szczech LA, et al. Association between pulse pressure and mortality in patients undergoing maintenance hemodialysis. JAMA 2002;287:1548-55. [ Links ]

83 Zager PG, Nikolic J, Brown RH, Campbell MA, Hunt WC, Peterson D, et al. &raquo;," &reg;,(r) &sect;,§ &shy;,­ &sup1;,¹ &sup2;,² &sup3;,³ &szlig;,ß &THORN;,Þ &thorn;,þ &times;,× &Uacute;,Ú &uacute;,ú &Ucirc;,Û &ucirc;,û &Ugrave;,Ù &ugrave;,ù &uml;,¨ &Uuml;,Ü &uuml;,ü &Yacute;,Ý &yacute;,ý &yen;,¥ &yuml;,ÿ &para;,¶ U &raquo;," &reg;,(r) &sect;,§ &shy;,­ &sup1;,¹ &sup2;,² &sup3;,³ &szlig;,ß &THORN;,Þ &thorn;,þ &times;,× &Uacute;,Ú &uacute;,ú &Ucirc;,Û &ucirc;,û &Ugrave;,Ù &ugrave;,ù &uml;,¨ &Uuml;,Ü &uuml;,ü &Yacute;,Ý &yacute;,ý &yen;,¥ &yuml;,ÿ &para;,¶ curve association of blood pressure and mortality in hemodialysis patients. Medical Directors of Dialysis Clinic, Inc. Kidney Int 1998;54:561-9. [ Links ]

84 Hirakata H, Nitta K, Inaba M, Shoji T, Fujii H, Kobayashi S, et al.; Japanese Society for Dialysis Therapy. Japanese Society for Dialysis Therapy guidelines for management of cardiovascular diseases in patients on chronic hemodialysis. Ther Apher Dial 2012;16:387-435. [ Links ]

85 Mc Causland FR, Waikar SS, Brunelli SM. Increased dietary sodium is independently associated with greater mortality among prevalent hemodialysis patients. Kidney Int 2012;82:204-11. [ Links ]

86 Chen W, Cheng LT, Wang T. Salt and fluid intake in the development of hypertension in peritoneal dialysis patients. Ren Fail 2007;29:427-32. [ Links ]

87 Wang AY, Brimble KS, Brunier G, Holt SG, Jha V, Johnson DW, et al. ISPD Cardiovascular and Metabolic Guidelines in Adult Peritoneal Dialysis Patients Part I - Assessment and Management of Various Cardiovascular Risk Factors. Perit Dial Int 2015;35:379-87. [ Links ]

88 Chazot C, Charra B, Vo Van C, Jean G, Vanel T, Calemard E, et al. The Janus-faced aspect of 'dry weight'. Nephrol Dial Transplant 1999;14:121-4. [ Links ]

89 Davies SJ, Davenport A. The role of bioimpedance and biomarkers in helping to aid clinical decision-making of volume assessments in dialysis patients. Kidney Int 2014;86:489-96. [ Links ]

90 Wizemann V, Schilling M. Dilemma of assessing volume state--the use and the limitations of a clinical score. Nephrol Dial Transplant 1995;10:2114-7. [ Links ]

91 Zhu F, Kuhlmann MK, Kotanko P, Seibert E, Leonard EF, Levin NW. A method for the estimation of hydration state during hemodialysis using a calf bioimpedance technique. Physiol Meas 2008;29:S503-16. [ Links ]

92 Wizemann V, Wabel P, Chamney P, Zaluska W, Moissl U, Rode C, et al. The mortality risk of overhydration in haemodialysis patients. Nephrol Dial Transplant 2009;24:1574-9. [ Links ]

93 Moissl U, Arias-Guillén M, Wabel P, Fontseré N, Carrera M, Campistol JM, et al. Bioimpedance-guided fluid management in hemodialysis patients. Clin J Am Soc Nephrol 2013;8:1575-82. [ Links ]

94 Brennan JM, Ronan A, Goonewardena S, Blair JE, Hammes M, Shah D, et al. Handcarried ultrasound measurement of the inferior vena cava for assessment of intravascular volume status in the outpatient hemodialysis clinic. Clin J Am Soc Nephrol 2006;1:749-53. [ Links ]

95 Zoccali C, Torino C, Tripepi R, Tripepi G, D'Arrigo G, Postorino M, et al.; Lung US in CKD Working Group. Pulmonary congestion predicts cardiac events and mortality in ESRD. J Am Soc Nephrol 2013;24:639-46. [ Links ]

96 Kayikcioglu M, Tumuklu M, Ozkahya M, Ozdogan O, Asci G, Duman S, et al. The benefit of salt restriction in the treatment of end-stage renal disease by haemodialysis. Nephrol Dial Transplant 2009;24:956-62. [ Links ]

97 Okada K, Abe M, Hagi C, Maruyama T, Maruyama N, Ito K, et al. Prolonged protective effect of short daily hemodialysis against dialysis-induced hypotension. Kidney Blood Press Res 2005;28:68-76. [ Links ]

98 Ayus JC, Mizani MR, Achinger SG, Thadhani R, Go AS, Lee S. Effects of short daily versus conventional hemodialysis on left ventricular hypertrophy and inflammatory markers: a prospective, controlled study. J Am Soc Nephrol 2005;16:2778-88. [ Links ]

99 Chan C, Floras JS, Miller JA, Pierratos A. Improvement in ejection fraction by nocturnal haemodialysis in end-stage renal failure patients with coexisting heart failure. Nephrol Dial Transplant 2002;17:1518-21. [ Links ]

100 Zimmerman DL, Ruzicka M, Hebert P, Fergusson D, Touyz RM, Burns KD. Short daily versus conventional hemodialysis for hypertensive patients: a randomized cross-over study. PLoS One 2014;9:e97135. [ Links ]

101 Tattersall J, Martin-Malo A, Pedrini L, Basci A, Canaud B, Fouque D, et al. EBPG guideline on dialysis strategies. Nephrol Dial Transplant 2007;22:ii5-21. [ Links ]

102 Jaber BL, Lee Y, Collins AJ, Hull AR, Kraus MA, McCarthy J, et al. Effect of daily hemodialysis on depressive symptoms and postdialysis recovery time: interim report from the FREEDOM (Following Rehabilitation, Economics and Everyday-Dialysis Outcome Measurements) Study. Am J Kidney Dis 2010;56:531-9. [ Links ]

103 Kotanko P, Garg AX, Depner T, Pierratos A, Chan CT, Levin NW, et al.; FHN Trial Group. Effects of frequent hemodialysis on blood pressure: Results from the randomized frequent hemodialysis network trials. Hemodial Int 2015;19:386-401. [ Links ]

104 Sulowicz W, Radziszewski A. Dialysis induced hypotension--a serious clinical problem in renal replacement therapy. Med Pregl 2007;60:14-20. [ Links ]

105 Chrysant SG, Chrysant GS. The pleiotropic effects of angiotensin receptor blockers. J Clin Hypertens (Greenwich) 2006;8:261-8. [ Links ]

106 Furgeson SB, Chonchol M. Beta-blockade in chronic dialysis patients. Semin Dial 2008;21:43-8. [ Links ]

107 Gadallah MF, el-Shahawy M, Andrews G, Ibrahim M, Ramdeen G, Hanna D, et al. Factors modulating cytosolic calcium. Role in lipid metabolism and cardiovascular morbidity and mortality in peritoneal dialysis patients. Adv Perit Dial 2001;17:29-36. [ Links ]

108 Agarwal R, Sinha AD. Cardiovascular protection with antihypertensive drugs in dialysis patients: systematic review and meta-analysis. Hypertension 2009;53:860-6. [ Links ]

109 Heerspink HJ, Ninomiya T, Zoungas S, de Zeeuw D, Grobbee DE, Jardine MJ, et al. Effect of lowering blood pressure on cardiovascular events and mortality in patients on dialysis: a systematic review and meta-analysis of randomised controlled trials. Lancet 2009;373:1009-15. [ Links ]

110 Ito Y, Mizuno M, Suzuki Y, Tamai H, Hiramatsu T, Ohashi H, et al.; Nagoya Spiro Study Group. Long-term effects of spironolactone in peritoneal dialysis patients. J Am Soc Nephrol 2014;25:1094-102. [ Links ]

111 Li PK, Chow KM, Wong TY, Leung CB, Szeto CC. Effects of an angiotensin-converting enzyme inhibitor on residual renal function in patients receiving peritoneal dialysis. A randomized, controlled study. Ann Intern Med 2003;139:105-12. [ Links ]

112 Suzuki H, Kanno Y, Sugahara S, Okada H, Nakamoto H. Effects of an angiotensin II receptor blocker, valsartan, on residual renal function in patients on CAPD. Am J Kidney Dis 2004;43:1056-64. [ Links ]

113 Suzuki H, Kanno Y, Sugahara S, Ikeda N, Shoda J, Takenaka T, et al. Effect of angiotensin receptor blockers on cardiovascular events in patients undergoing hemodialysis: an open-label randomized controlled trial. Am J Kidney Dis 2008;52:501-6. [ Links ]

114 Cice G, Ferrara L, D'Andrea A, D'Isa S, Di Benedetto A, Cittadini A, et al. Carvedilol increases two-year survivalin dialysis patients with dilated cardiomyopathy: a prospective, placebo-controlled trial. J Am Coll Cardiol 2003;41:1438-44. [ Links ]

115 Matsumoto N, Ishimitsu T, Okamura A, Seta H, Takahashi M, Matsuoka H. Effects of imidapril on left ventricular mass in chronic hemodialysis patients. Hypertens Res 2006;29:253-60. [ Links ]

116 Takahashi A, Takase H, Toriyama T, Sugiura T, Kurita Y, Ueda R, et al. Candesartan, an angiotensin II type-1 receptor blocker, reduces cardiovascular events in patients on chronic haemodialysis--a randomized study. Nephrol Dial Transplant 2006;21:2507-12. [ Links ]

117 Bakris GL, Hart P, Ritz E. Beta blockers in the management of chronic kidney disease. Kidney Int 2006;70:1905-13. [ Links ]

118 Badve SV, Roberts MA, Hawley CM, Cass A, Garg AX, Krum H, et al. Effects of beta-adrenergic antagonists in patients with chronic kidney disease: a systematic review and meta-analysis. J Am Coll Cardiol 2011;58:1152-61. [ Links ]

119 Nakao K, Makino H, Morita S, Takahashi Y, Akizawa T, Saito A, et al.; J-DOPPS Investigators Group. Beta-blocker prescription and outcomes in hemodialysis patients from the Japan Dialysis Outcomes and Practice Patterns Study. Nephron Clin Pract 2009;113:c132-9. [ Links ]

120 Gervasini G, Robles NR. Potential beneficial effects of sacubitril-valsartan in renal disease: a new field for a new drug. Expert Opin Investig Drugs 2017;26:651-9. [ Links ]

121 Weir MA, Dixon SN, Fleet JL, Roberts MA, Hackam DG, Oliver MJ, et al. ß-Blocker dialyzability and mortality in older patients receiving hemodialysis. J Am Soc Nephrol 2015;26:987-96. [ Links ]

122 Agarwal R, Lewis R, Davis JL, Becker B. Lisinopril therapy for hemodialysis hypertension: hemodynamic and endocrine responses. Am J Kidney Dis 2001;38:1245-50. [ Links ]

Received: July 16, 2018; Accepted: September 05, 2018

Correspondence to: Sérgio Gardano Elias Bucharles. E-mail: sergio_bucharles@hotmail.com

Creative Commons License This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.