Hypertension in patients on dialysis

INTRODUCTION — Hypertension is common among patients on dialysis [1]. This topic reviews the epidemiology, pathogenesis, and treatment of hypertension in patients on dialysis.

Hypertension among patients with acute or chronic kidney disease who are not on dialysis is discussed elsewhere.

●(See "Overview of hypertension in acute and chronic kidney disease".)

●(See "Antihypertensive therapy and progression of nondiabetic chronic kidney disease in adults".)

Hypertension in the general adult population is discussed elsewhere.

●(See "Overview of hypertension in adults".)

●(See "Choice of drug therapy in primary (essential) hypertension".)

●(See "Goal blood pressure in adults with hypertension".)

EPIDEMIOLOGY

●Prevalence – Hypertension is a common finding in patients on dialysis. Prevalence estimates vary widely among studies because of differences in the definition of hypertension and in methods of measuring blood pressure (BP; ie, either before and after hemodialysis or using ambulatory BP recordings). Based upon multiple studies, over 50 to 60 percent of patients on hemodialysis (up to 85 percent in some reports) and nearly 30 percent of patients on peritoneal dialysis are hypertensive [2-6]. In one multicenter trial that included 2535 adult patients on hemodialysis, the prevalence of hypertension, defined as one-week average predialysis systolic BP measurements of 150 mmHg or diastolic BP of 85 mmHg or the use of antihypertensive medications, was 86 percent [5,6].

Hypertension is more common among patients who are just initiating dialysis (greater than 80 percent) because almost all such patients are volume overloaded [7]. Persistent hypertension often reflects inadequate volume control despite the initiation of dialysis [4,8]. (See 'Pathogenesis' below.)

●BP and mortality – Multiple large observational studies have demonstrated a U-shaped relationship between BP and mortality among patients on dialysis [9-22]. This U-shaped relationship suggests that both low and high BPs are associated with a higher mortality compared with mid-range BPs. However, much of the BP and mortality data in patients on hemodialysis are complicated by the use of in-center dialysis unit pre- and postdialysis BP values; BPs recorded on an interdialytic day are monotonically associated with mortality [23].

PATHOGENESIS — Volume expansion is the major cause of hypertension in patients on dialysis [24,25]. Volume overload leads to an elevation in blood pressure (BP) via the combination of a rise in cardiac output and high systemic vascular resistance [7,26]. The role of volume expansion is supported by studies that have shown improvement in BP with volume reduction [27-29].

The removal of the excess sodium and reduction in target dry weight can result in the normalization of BP in >60 percent of patients on hemodialysis and in many patients on peritoneal dialysis [7,27,30-35].

Sympathetic overactivity, activation of the renin-angiotensin system, and arteriosclerosis also contribute to hypertension in patients on hemodialysis [36-38].

Other potential contributors include changes in endothelium-derived vasoactive peptides [39-42], increases in intracellular calcium [43,44], and decreases in renalase [45]. Renalase is a catecholamine-metabolizing enzyme released by the kidney in response to catecholamine surge.

Elevated BP may also be associated with use of erythropoiesis-stimulating agents, over-the counter drugs such as nasal decongestants and nonsteroidal anti-inflammatory drugs (NSAIDs), illicit drugs such as cocaine, and herbal remedies such as ma huang and St. John's wort [7,26,46,47]. (See "Overview of hypertension in adults", section on 'Primary hypertension'.)

MONITORING AND DIAGNOSIS — Ambulatory blood pressure monitoring (ABPM) is considered the gold standard for the diagnosis of hypertension [48]. Although ABPM provides reproducible readings and correlates with outcomes among patients on dialysis [49-51], ABPM is generally not used clinically, as it is cumbersome and poorly suited to day-to-day management of hypertension.

Our approach to monitoring blood pressure (BP) in patients with end-stage kidney disease varies according to dialysis modality:

Hemodialysis

●Preferred BP measurement strategy – For patients on hemodialysis, we use self-recorded home BPs to monitor BP and diagnose hypertension. To preserve dialysis access, we instruct patients with an upper extremity arteriovenous fistula or graft to obtain home BPs from the contralateral arm. We instruct patients on conventional thrice weekly hemodialysis to check home BP readings twice daily for four days after the midweek dialysis treatment and to provide the measurements for averaging and review. Ideally, home BPs should not be checked in the immediate peridialytic period; for example, a patient dialyzed Wednesday morning should start checking home BPs Wednesday late afternoon or evening, whereas a patient dialyzed Wednesday afternoon or evening should start checking home BPs Thursday morning. Although the optimal frequency of monitoring is not known, we suggest home BP monitoring at monthly intervals [52-54]. Self-recorded home BP readings are efficient, accurate, and correlate with ABPM [49,52,55,56] and with outcomes [9,10,23,57]. The preferred technique of self-measured BP measurement is detailed elsewhere. (See "Out-of-office blood pressure measurement: Ambulatory and self-measured blood pressure monitoring", section on 'Self-measured blood pressure (SMBP)'.)

If ABPM is used to confirm home-recorded BP readings, it is started after the midweek dialysis treatment and continued over the 44-hour interdialytic period to account for volume-related increases in BP [49,55]. ABPM generally shows a linear increase in BP as volume accrues.

We do not use in-center dialysis unit pre- and postdialysis BP measurements to diagnose hypertension or titrate antihypertensive therapy. Although BP is closely monitored throughout the dialysis treatment to assess the hemodynamic stability of the patient during the treatment, the pre- or postdialysis BP readings correlate only weakly with ABPM. They associate inversely with clinical outcomes, which is counterintuitive [11,12]. Predialysis BP readings tend to overestimate and postdialysis readings underestimate BP readings obtained by ABPM, and the degree of bias is variable. In one systematic review of studies, compared with 44-hour ABPM, predialysis systolic BP was variably 42 mmHg higher or 25 mmHg lower, and postdialysis systolic BP was 33 mmHg higher to 36 mmHg lower [58].

In contrast to in-center pre- and postdialysis readings, BP readings obtained outside the dialysis unit (either by ABPM or self-recorded home measurement) are directly related to all-cause mortality [9,10,23,57]. As an example, a 2015 study showed that a single recording of systolic BP measured outside the dialysis unit was directly related to mortality (hazard ratio [HR] 1.26, 95% CI 1.14-1.40) for every 10 mmHg increase [23].

●Alternate BP measurement strategy – If home BP monitoring is not possible or is unavailable, as a last resort, we use midweek median intradialytic systolic BP. As an example, in a patient who dialyzes Monday-Wednesday-Friday, if the median intradialytic systolic BP is 146 mmHg on Wednesday, the patient is very likely to be hypertensive. In one study, the midweek median intradialytic BP of 140 mmHg was approximately 80 percent sensitive and approximately 80 percent specific in diagnosing hypertension among patients on dialysis. For median diastolic BP of 80 mmHg, the sensitivity and specificity for diagnosing hypertension in the interdialytic period was approximately 75 percent each [59]. Furthermore, median intradialytic BP can track changes evoked by probing dry weight in these patients [60]. Nonetheless, the clinical use of median intradialytic systolic BP is suboptimal since it has wide limits of agreement with 44-hour ambulatory systolic BP, ranging from 16 to 20 mmHg.

Peritoneal dialysis — For patients on peritoneal dialysis, we use self-recorded home BPs to monitor BP and diagnose hypertension. We instruct patients to check home BP readings twice daily for a minimum of three days and to provide the measurements for averaging and review. Although the optimal frequency of monitoring is not known, we suggest home BP monitoring at monthly intervals. The preferred technique of self-measured blood pressure measurement is detailed elsewhere. (See "Out-of-office blood pressure measurement: Ambulatory and self-measured blood pressure monitoring", section on 'Self-measured blood pressure (SMBP)'.)

If home BP monitoring is not possible or is unavailable, we use office BP measurements obtained at the patient's monthly nephrology office visit. If available, we prefer automated office blood pressure measurement (AOBP), which provides multiple consecutive unattended BP readings, rather than routine office-based BP measurement. The optimal technique of office-based BP measurement is detailed elsewhere. (See "Blood pressure measurement in the diagnosis and management of hypertension in adults", section on 'Office-based blood pressure measurement'.)

In the general population and among patients with chronic kidney disease, self-recorded BP measurements correlate more closely with the results of 24-hour or daytime ABPM than with office-based measurements [61-64].

BENEFITS OF TREATING HYPERTENSION — Multiple studies and meta-analyses of randomized, controlled trials in patients on dialysis have suggested a benefit of using antihypertensive agents to lower blood pressure (BP) on cardiovascular (CV) events and CV mortality [13,65-69]. The best data are from two meta-analyses:

●A 2009 systematic review and meta-analysis of eight randomized, controlled trials that enrolled 1679 patients on dialysis found that lowering BP with antihypertensive therapy was associated with decreased risks of CV events (relative risk [RR] 0.71, 95% CI 0.55-0.92), all-cause mortality (RR 0.80, 95% CI 0.66-0.96), and CV mortality (RR 0.71, 95% CI 0.50-0.99) [68].

●A second 2009 meta-analysis including five randomized trials with 1202 patients on hemodialysis showed that, compared with placebo or control therapy, BP lowering with antihypertensive therapy resulted in a 31 percent reduction in the risk of CV events (pooled hazard ratio [HR] 0.69, 95% CI 0.56-0.84) [69].

TREATMENT — The optimal blood pressure (BP) goal and the interventions that are available to treat hypertension in patients on dialysis are discussed here.

Blood pressure target — The threshold BP that should be treated is unknown; BP target ranges for patients on dialysis have been extrapolated from studies in the nondialysis patient population. In addition, BP targets may need to be individualized based on patient frailty, expected survival, and symptoms such as dizziness or light-headedness. BP targets for patients on hemodialysis and for patients on peritoneal dialysis are discussed below:

●Patients on hemodialysis – In patients on hemodialysis, we target an interdialytic BP of <140/80 using home BPs. We preferably use self-measured home BP to achieve this target for reasons discussed above. (See 'Monitoring and diagnosis' above.)

If interdialytic self-measured home BP is not available, targeting a midweek median intradialytic BP of <140/80 mmHg appears to be a reasonable alternative strategy. We calculate the midweek median BP from all the BPs measured during a midweek dialysis session (eg, on Wednesday for a patient receiving dialysis on Mondays, Wednesdays, and Fridays).

We do not use a predialysis BP target to control hypertension. Targeting predialysis BPs is not helpful. As an example, one pilot trial evaluated the target predialysis BP in patients receiving dialysis [70]. The trial randomly assigned 126 long-term hemodialysis patients to one of two BP goals: an intensive arm (predialysis systolic BP of 110 to 140 mmHg) and a standard arm (predialysis systolic BP of 155 to 165 mmHg). Compared with patients in the standard arm, those in the intensive arm had a higher risk of recurrent hospitalization, vascular access thrombosis, and intradialytic hypotension.

●Patients on peritoneal dialysis – In patients on peritoneal dialysis, we target a BP of <130/80 mmHg using home BPs or automated office blood pressure measurement (AOBP), or a target of <140/90 mmHg using routine office-based measurements. We preferably use home BP for reasons discussed above (see 'Monitoring and diagnosis' above). The target of <140/90 mmHg is consistent with guidelines from the International Society of Peritoneal Dialysis [71].

There are no large-scale trials that define optimal BP targets among patients on hemodialysis or peritoneal dialysis. Our assessment of the best target BP is based upon findings reported in observational studies combined with our clinical experience managing patients on dialysis.

Interventions — The two main treatment interventions to control BP are as follows:

●Reducing the target dry weight to achieve euvolemia

●Antihypertensive medications

If possible, the target dry weight should be adjusted before antihypertensive agents are added. However, patients are often on multiple antihypertensive agents when they start maintenance dialysis. Among such patients, the approach will vary depending on severity of hypertension and hemodynamic stability during dialysis. As an example, in some patients on dialysis, ultrafiltration is limited because of hypotension; such patients may benefit from tapering antihypertensive agents. In other patients who have severe hypertension, antihypertensive agents may need to be continued while the target dry weight is gradually reduced.

Achieving optimal dry weight — Reducing the target dry weight gradually can normalize the BP or make the hypertension easier to control in a vast majority of patients on dialysis [33,72]. The exact definition of target dry weight remains uncertain, but multiple definitions have been suggested [73-75]. We believe that the best definition of dry weight is the lowest tolerated weight at which there are minimal signs or symptoms of either hypovolemia or hypervolemia [76].

Assessment of volume status — A careful clinical assessment of volume status is necessary to achieve an optimal dry weight.

●History and physical examination – Patient history and physical examination are essential components of the volume status assessment. The patient should be questioned about missing dialysis treatments or cutting them short, since underdialysis commonly leads to volume overload. A recent hospitalization may suggest loss of lean body mass, especially after a catabolic illness such as pneumonia or long bone fracture. Symptoms that suggest orthostatic hypotension (such as lightheadedness) and, for patients on hemodialysis, intradialytic symptoms such as muscle cramps may indicate that the dry weight is below desired. However, muscle cramps may not be a reliable indicator of hypovolemia, especially when they do not improve despite an increase in dry weight.

A physical examination includes an assessment for presence of increased jugular venous pulse, peripheral or pulmonary edema, and ascites (suggesting volume overload) at a given weight and BP.

●Other methods – If used, other methods of assessing volume status should function as adjuncts, rather than as alternatives, to the clinical assessment of the patient.

Bioimpedance analysis [77,78], relative plasma volume (RPV) monitoring [79,80], measurement of the inferior cava diameter [81-83], and plasma natriuretic peptides (particularly atrial and B-type) concentrations [84,85] have been used to assess dry weight. These methods are not commonly used clinically, although studies have suggested utility, particularly of bioimpedance analysis and RPV monitoring [77,79,80]. None of these methods for determining dry weight have demonstrated superiority over clinical assessment alone [80,84,86-88].

An emerging strategy to assess volume excess is lung ultrasound, which can be used to measure lung water as a marker of lung congestion. One trial compared lung ultrasound-guided dry weight reduction versus usual care on BP improvement among 71 hemodialysis patients [89-91]. At 12 months, lung ultrasound-guided dry weight reduction was greater in the ultrasound group (-2 versus +0.5 kg), and accompanied by a greater decline in 44-hour ambulatory systolic (6 versus 0.5 mmHg) and diastolic (4 versus 1 mmHg) BP, ultrasound B lines (metric of lung water, -5 lines versus +6 lines), and rate of intradialytic hypotension. However, this was a small trial, and these findings need to be replicated in larger, more diverse populations before it can be introduced into routine clinical care.

Subclinical volume excess — In many patients with hypertension, volume excess may be present despite the clinical appearance of euvolemia (see 'Assessment of volume status' above). Therefore, we attempt to reduce dry weight without clinical evidence of volume expansion in the following scenarios:

●Patients just initiating maintenance dialysis who are either hypertensive (as defined above) or who are taking antihypertensive agents

●Patients on dialysis with worsening BP control of unknown cause

●Patients on dialysis requiring additional antihypertensive medications, or dose escalations of existing medications, to maintain adequate BP control

How to reduce target dry weight — The reduction in dry weight is best done gradually; we reduce the target dry weight over days to weeks [7,27,30,31,66,92-96]. An important component of successfully attaining a lower dry weight is to minimize fluid accumulation, which, for patients on hemodialysis, predominantly occurs in the interdialytic period.

●Limit salt intake for all patients – Limiting dietary salt is the best way to limit fluid intake because salt intake drives thirst. It is not helpful to restrict fluid without restricting salt.

All patients should adhere to a restricted salt diet (1500 to 2000 mg of sodium/day) [66,97,98]. However, patient adherence to a low-sodium diet is often suboptimal.

●Patients on hemodialysis – We reduce the target dry weight by approximately 0.5 kg per dialysis session. In patients who are unable to tolerate this, we attempt 0.2 kg per session.

Patients should minimize interdialytic weight gain in order to limit the amount of fluid that needs to be removed in an individual session. Patients with greater weight gain in between dialysis sessions (eg, >2 to 3 kg) often have difficulty achieving the previous target dry weight, especially at optimal rates of ultrafiltration. (See "Prescribing and assessing adequate hemodialysis", section on 'Patient-specific parameters'.)

In patients who have clinical evidence of volume excess but in whom it is difficult to reduce the target dry weight, we use the following approach:

•Increase dialysis time – Increasing the length or frequency of sessions is often effective in reducing target dry weight [99].

The utility of lengthier dialysis sessions was demonstrated in a large dialysis center in Tassin, France, where a standard regimen is eight hours, three times per week [31,100-102]. This regimen was associated with the maintenance of normotension without medications in almost all patients [31,100-102]. The improved BP was largely attributed to optimal volume control, although other factors may contribute, such as decreased afferent renal nerve activity and efferent sympathetic activation [36]. However, this regimen is not widely used in in-center hemodialysis. (See "Patient survival and maintenance dialysis", section on 'Adequacy of dialysis'.)

The efficacy of more frequent dialysis in achieving BP control is demonstrated by nocturnal hemodialysis, in which dialysis is performed six or seven nights a week during sleep (usually 6 to 12 hours in total) [103]. Almost all patients become normotensive without medications. (See "Technical aspects of nocturnal hemodialysis".)

Short daily hemodialysis may also be associated with better BP control. (See "Short daily hemodialysis".)

•Reduce dialysate sodium – If increasing the dialysis time is ineffective, we reduce the dialysate sodium concentration.

The use of standard sodium prescriptions leads to decreased sodium loss during dialysis and mild increases in serum sodium values postdialysis [104]. This results in increased thirst, large interdialytic weight gains, and corresponding difficulty achieving an optimal dry weight. A lower dialysate sodium concentration may result in lower antihypertensive medication requirements and decreased BP [105]. The dialysate sodium should be reduced gradually (ie, 1 mEq/L every three to four weeks) to approximately 135 mEq/L. Because lower dialysate sodium concentrations may be associated with a greater risk of intradialytic hypotension [106], patients should be encouraged to report symptoms of lightheadedness, muscle cramps, and nausea that occur during dialysis.

The dialysate sodium may be reduced in a fixed or variable fashion.

The effect of a variable reduction in dialysate sodium (also known as sodium modeling) on BP was evaluated in one randomized, crossover study [107]. A programmed decrease in sodium dialysate concentration from 155 to 135 mEq/L was compared with the standard stable sodium dialysate concentration of 140 mEq/L [107]. Postdialysis BP and antihypertensive use were reduced when patients were dialyzed with a variable sodium prescription.

A fixed lower dialysate sodium concentration in combination with sodium restriction was evaluated in a small, uncontrolled study [108]. Eight hypertensive hemodialysis patients were dialyzed against a gradually lowered sodium dialysate concentration (140 to 135 mEq/L at a rate of 1 mEq/L every three to four weeks) and were encouraged to limit salt intake to <6 g/day [108]. At study end, the mean arterial pressure was lower, and antihypertensive medications were no longer required in four patients. However, adherence to the diet was difficult, and the frequency of muscle cramps during dialysis was increased. This regimen engenders the risk of episodic hypotension and should be instituted cautiously (ie, with close observation).

●Patients on peritoneal dialysis – For patients on peritoneal dialysis who do not have clinical evidence of volume expansion but in whom we attempt to reduce target dry weight (see 'Subclinical volume excess' above), we challenge the dry weight by 0.5 to 1.0 kg per week. In patients who have clinical evidence of volume expansion, we reduce the target dry weight more rapidly. The approach to volume control for patients on peritoneal dialysis is detailed separately. (See "Management of hypervolemia in patients on peritoneal dialysis".)

Antihypertensive medications — Many patients on dialysis will require antihypertensive agents to control BP despite achieving optimal dry weight. The optimal antihypertensive regimen for patients on dialysis is not known. Our approach to managing hypertension among patients on dialysis who require medications after optimization of volume status (see 'Achieving optimal dry weight' above) is as follows:

●Our first-choice antihypertensive agent is a beta blocker (BB), even among patients previously controlled with another agent. Among the available BBs, we prefer atenolol, but other BBs are acceptable alternatives. Dosing varies by modality of dialysis:

•Among patients receiving hemodialysis, we dose atenolol postdialysis thrice weekly. We typically start it at 25 or 50 mg depending upon the severity of hypertension. The maximum dose that we use among patients on hemodialysis is 100 mg thrice weekly.

•Among patients receiving peritoneal dialysis, we dose atenolol once daily. We typically start it at 25 or 50 mg once daily depending upon the severity of hypertension. The maximum daily dose that we use among patients on peritoneal dialysis is 50 mg once daily.

A dose-limiting side effect of BBs is bradycardia. Among patients with symptomatic bradycardia from BBs (eg, lightheadedness, presyncope or syncope, exercise intolerance), we reduce the dose of the BB. Among patients with asymptomatic bradycardia, we avoid increasing the BB dose once the heart rate is 50 beats per minute or below and reduce the dose when the heart rate is 40 beats per minute or below. Side effects of BBs are discussed at length elsewhere. (See "Major side effects of beta blockers".)

●Our second-choice agent is a dihydropyridine calcium channel blocker (CCB), such as amlodipine 10 mg dosed daily. We add amlodipine among patients who have BPs that are not adequately controlled with the maximum dose BB or among patients who develop intolerable side effects (eg, bradycardia) to the BB. CCBs are not cleared by dialysis and, therefore, do not need to be supplemented or dosed postdialysis. Side effects of CCBs are discussed at length elsewhere. (See "Major side effects and safety of calcium channel blockers".)

●Our third-choice agent is an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB). We add an ACE inhibitor or ARB among patients with BPs that are inadequately controlled with a BB and a CCB and among patients who have inadequately controlled BP with one and intolerance to another. However, for patients on dialysis who still make urine, some experts prefer to use an ACE inhibitor or ARB as first-line antihypertensive therapy because of the potential benefit of preserving residual kidney function. (See "Residual kidney function in kidney failure", section on 'Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers'.)

Side effects of ACE inhibitors and ARBs are discussed below and at length elsewhere. (See "Major side effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers".)

The management of patients who remain hypertensive despite maximally tolerated doses of BB, CCB, and either ACE inhibitor or ARB is discussed below. (See 'Resistant hypertension' below.)

Our preference for BBs as the first-line agent is based upon findings from the Hypertension in Hemodialysis Patients Treated with Atenolol or Lisinopril trial in which 200 patients were randomly assigned to receive either drug [55]. At 12 months, compared with lisinopril, atenolol led to a numerically greater reduction in BP using the 44-hour interdialytic ambulatory BP monitoring (mean reduction -21/-13 versus -18/-10 mmHg) and the self-measured home BPs (mean reduction -25/-12 versus -19/-10 mmHg); these differences were not statistically significant. Over the course of the trial, compared with patients in the lisinopril group, those in the atenolol group required fewer antihypertensive medications despite a lesser degree of reduction in their dry weight. Additionally, there were fewer serious cardiovascular (CV) events including CV death, myocardial infarction, stroke, and hospitalization for heart failure in the atenolol group compared with the lisinopril group (20 events among 16 patients versus 43 events among 28 patients), leading to early termination of the trial.

Our next preference for CCBs is based upon their efficacy and tolerance in addition to their beneficial effect on CV outcomes in dialysis patients [109-111]. In one trial, compared with patients randomly assigned to placebo, those assigned to amlodipine had a reduction in the composite of all-cause mortality and CV events (hazard ratio [HR] 0.53, 95% CI 0.31-0.93). Amlodipine led to a clinically meaningful but statistically nonsignificant reduction in all-cause mortality (12 percent with amlodipine and 17 percent with placebo) [111].

We do not use nondihydropyridine CCBs (such as verapamil or diltiazem) because drug interactions with these agents are common and bradycardia can occur if dosed concomitantly with a BB.

We offer ACE inhibitors and ARBs only to patients who have an elevated BP despite maximally tolerated doses of BBs and CCBs. This is because ACE inhibitors or ARBs lead to modest reduction in BPs and no reduction in fatal and nonfatal CV events. As examples, in a 2010 meta-analysis of trial data including 837 patients on hemodialysis, there was no significant reduction in BP or fatal and nonfatal CV events among patients treated with ACE inhibitors or ARBs compared with those in the standard care group [112]. In a subsequent trial of 469 hemodialysis patients, compared with standard care, patients randomly assigned to olmesartan had no significant reduction in BP (mean difference in BP of 0.9 mmHg) or in the incidence of fatal and nonfatal CV events (HR 1.00, 95% CI 0.62-1.52) [113]. Another smaller trial reported similar findings [114].

In addition, ACE inhibitors and ARBs can cause hyperkalemia [55], hypotension [55,114], reduction in the effect of erythropoiesis-stimulating agents, and anaphylactoid reaction in patients dialyzed with an AN69 dialyzer [115], thereby lowering the overall appeal of these agents. (See "Major side effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers".)

RESISTANT HYPERTENSION — Some dialysis patients are resistant to both volume control and initial antihypertensive medications. Factors that can contribute to resistant hypertension include (see "Definition, risk factors, and evaluation of resistant hypertension" and "Treatment of resistant hypertension"):

●Nonadherence to the antihypertensive regimen (see "Patient adherence and the treatment of hypertension")

●Concurrent use of a medication that can raise blood pressure (BP; such as nonsteroidal anti-inflammatory drugs [NSAIDs] or erythropoietin-stimulating agents) (see 'Pathogenesis' above)

●Inadequate dialysis (less than four hours per session, thrice weekly) (see "Prescribing and assessing adequate hemodialysis")

●Renovascular hypertension (see "Establishing the diagnosis of renovascular hypertension")

●Expanding cyst size among patients with polycystic kidney disease (see "Autosomal dominant polycystic kidney disease (ADPKD): Evaluation and management of hypertension")

Nonadherence with medications is a common cause of resistant hypertension. Chronically nonadherent hypertensive patients who refuse to take medications at home may benefit from the administration of long-acting antihypertensive medications in the dialysis unit [116].

If a treatable cause cannot be found, the vasodilator minoxidil may be added to the antihypertensive regimen. A central sympathetic agonist (ie, clonidine or guanfacine) is used less frequently than minoxidil because of adverse effects involving the central nervous system, and because of the possible potentiation of beta blocker (BB) mediated bradycardia. Some clinicians have found clonidine patches to be effective and well tolerated, but this is not a universal finding [115,116]. Guanfacine may be less sedating than clonidine.

We generally do not use mineralocorticoid receptor antagonists in patients on dialysis because of the potential risk of hyperkalemia [117-119]. Mineralocorticoid receptor antagonists (eg, spironolactone) are commonly used in nondialysis patients with resistant hypertension, and two trials reported very large benefits on cardiovascular (CV) mortality from spironolactone in patients receiving dialysis [120,121]. Effects of this magnitude are rarely if ever observed in rigorous CV trials; in addition, the findings have not been independently confirmed.

More data are needed before renal denervation can be recommended in patients on dialysis (see "Treatment of resistant hypertension", section on 'Renal denervation'). Renal denervation is a therapy in which sympathetic nerves innervating the kidney are ablated for BP control. This method was evaluated in a small nonrandomized trial of 24 patients on hemodialysis who had resistant hypertension despite maximal medical therapy with confirmed adherence [122]. Over a follow-up period of one year, patients treated with renal denervation in addition to medical therapy had a substantial and sustained reduction in BP compared with patients on medical therapy alone (32/18 mmHg versus 7/3 mmHg).

Bilateral nephrectomy is no longer performed ever since effective antihypertensive medications became available.

HYPERTENSION DURING HEMODIALYSIS — Some patients develop paradoxical hypertension in the later stages of the hemodialysis treatment, a time at which most of the excess fluid has already been removed. Limited observational evidence suggests that this increase in blood pressure (BP) is associated with adverse outcomes [123]. The pathogenesis is unclear, although evidence suggests that contributing factors include volume excess [124], interdialytic hypertension [125], and altered nitric oxide/endothelin-1 balance and/or endothelial dysfunction [126,127].

The optimal approach to intradialytic hypertension is not known. The following interventions, which may be used in combination but should be initiated or adjusted singly, may be effective:

●Challenging the dry weight [79].

●Switching atenolol to carvedilol, which blocks endothelin-1 release. In a 12-week pilot study, the initiation of carvedilol titrated to 50 mg twice daily was associated with a decrease in the frequency of intradialytic hypertensive episodes from 77 to 28 percent of hemodialysis sessions.

●Using a dialysate sodium concentration that is lower than the patient's serum sodium. The efficacy of this intervention was suggested by a three-week randomized, crossover trial that compared the effect of high- and low-dialysate sodium concentrations on systolic BP among 16 patients with intradialytic hypertension [128].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Dialysis".)

SUMMARY AND RECOMMENDATIONS

●Epidemiology and pathogenesis – Hypertension is a common finding in patients on dialysis, particularly at initiation. Volume expansion is the major cause of hypertension in patients on dialysis, although sympathetic overactivity, activation of the renin-angiotensin system, and arteriosclerosis also contribute. (See 'Epidemiology' above and 'Pathogenesis' above.)

●Blood pressure (BP) assessment – For patients on dialysis, we use self-recorded home BPs to monitor BP and diagnose hypertension. Self-recorded home BP readings are efficient, accurate, and correlate with readings obtained by ambulatory blood pressure monitoring (ABPM). For patients on hemodialysis, we do not use pre- and postdialysis BP measurements to diagnose hypertension and inform antihypertensive therapy, since these measurements do not correlate with ABPM or with clinical outcomes. (See 'Monitoring and diagnosis' above.)

If home BP monitoring is not possible or feasible, our approach varies by dialysis modality:

•For patients on hemodialysis, we use the midweek median intradialytic systolic BP. (See 'Hemodialysis' above.)

•For patients on peritoneal dialysis, we use office BP measurements obtained at the patient's monthly nephrology office visit. If available, we prefer automated office blood pressure measurement (AOBP), which provides multiple consecutive unattended BP readings, rather than routine office-based BP measurement. (See 'Peritoneal dialysis' above.)

●BP target – The threshold BP that should be treated is unknown.

•For patients on hemodialysis, we suggest targeting an interdialytic BP of <140/80 mmHg using home BPs (Grade 2C). If interdialytic home BPs are not available, targeting a midweek median intradialytic BP of <140/80 mmHg is a reasonable alternative strategy. (See 'Blood pressure target' above.)

•For patients on peritoneal dialysis, we suggest targeting a BP of <130/80 mmHg using home BPs (Grade 2C). If home BPs are unavailable, we target a BP of <130/80 mmHg using AOBP, or a target of <140/90 mmHg using routine office-based measurements. (See 'Blood pressure target' above.)

●Treatment interventions – The primary strategy to improve BP in a patient on dialysis is to optimize volume status. BP treatment consists of reducing target dry weight to achieve euvolemia and pharmacologic interventions. We use the history and physical examination to assess volume status and individualize optimal target dry weight. (See 'Interventions' above and 'Assessment of volume status' above.)

●Reducing target dry weight – We reduce the target weight over days to weeks. An important component of successfully attaining a lower dry weight is to minimize fluid accumulation, which, for patients on hemodialysis, predominantly occurs in the interdialytic period. Limiting salt intake prevents thirst and is the best way to limit fluid intake. For some patients on hemodialysis, increasing the length and/or frequency of dialysis sessions is necessary to achieve an optimal dry weight. (See 'How to reduce target dry weight' above.)

●Antihypertensive medications – Many patients on dialysis require antihypertensive agents. The optimal agent is not known. Our approach is as follows (see 'Antihypertensive medications' above):

•Among patients on dialysis who need antihypertensive therapy, we suggest treatment with a beta blocker (BB) rather than another antihypertensive agent (Grade 2C). Atenolol is our usual choice, but other BBs are acceptable alternatives. Among patients on hemodialysis, we dose atenolol thrice weekly with a starting dose of 25 mg up to a maximum of 100 mg. Among patients on peritoneal dialysis, we dose atenolol daily with a starting dose of 25 mg up to a maximum dose of 50 mg. We reduce the dose of the BB for symptomatic bradycardia and if the heart rate is at or below 40 beats per minute. We stop increasing the dose of the BB if the heart rate is at or below 50 beats per minute.

•Among patients who have BPs that are not adequately controlled with the maximum dose BB or who develop intolerable side effects (eg, bradycardia) to the BB, we add calcium channel blockers (CCBs), such as amlodipine 10 mg.

•Among patients who have BPs that are inadequately controlled with a BB and a CCB and among patients who have inadequately controlled BP with one and intolerance to another, we add an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB). However, for patients on dialysis who still make urine, some experts prefer to use an ACE inhibitor or ARB as first-line antihypertensive therapy because of the potential benefit of preserving residual kidney function. (See "Residual kidney function in kidney failure", section on 'Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers'.)

●Resistant hypertension – Patients who have BPs that are uncontrolled despite use of maximally tolerated doses of a BB, CCB, and an ACE or ARB have resistant hypertension. Such patients require an evaluation for possible underlying causes and possible treatment with additional antihypertensive agents such as minoxidil. (See 'Resistant hypertension' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges William Henrich, MD, MACP and Lionel U Mailloux, MD, FACP, who contributed to earlier versions of this topic review.