Dihydropyridine and non-dihydropyridine calcium channel blockers can also be used for BP control in hemodialysis patient. A small prospective study showed a trend toward lower cardiovascular mortality in patients treated with amlodipine and a reduction in composite of all-cause mortality and cardiovascular events.(Tepel et al. 2008) Amlodipine was effective in reducing systolic BP in the treated group.

Beta blockers have an important role in the management of hemodialysis patients with cardiovascular comorbidities, including systolic heart failure and coronary artery disease. Among patients on hemodialysis with LVH, atenolol administered three times a week after dialysis was shown to be more effective in lowering BP, decreasing risk of serious cardiovascular events and all cause hospitalizations when compared to lisinopril dosed three times a week (Agarwal et al. 2014). It is again important to consider pharmacokinetics of various b-blockers. Atenolol for example is primarily removed by the kidney itself and actually requires dose reduction in hemodialysis patients (Table 2). Given its longer half-life in hemodialysis patients, it may be a good option to use in patients with poor compliance since it can be dosed three times a week after dialysis. On the other hand, carvedilol does not require dose adjustment in hemodialysis patients and its alpha 1-adrenergic blocking activity may improve BP control beyond other b-blockers, but could also potentiate symptoms of postural hypotension.

Hydralazine and clonidine can be used for BP control in hemodialysis patients but both medications require multiple dosing during the day and may lead to reduced compliance especially in hemodialysis patients who already have large pill burden. An alternative option is transdermal clonidine patch which requires dosing once a week. Minoxidil is another potent vasodilator that can be dosed once a day but should be combined with beta blocker to prevent reflex tachycardia.

Poor adherence to medications in hemodialysis patients is well recognized and likely contributes to uncontrolled BP. One study reported that only 48 % of hemodialysis patients were adherent to their treatment.(Neri et al. 2011) Multiple strategies have been suggested to help improve compliance with antihypertensives in hemodialysis patients, but the most important is to simplify the medication regimen. For example, use of longer acting formulations such as transdermal clonidine patch reduces pill burden. Directly observed therapy using other long acting antihypertensive such as atenolol and certain ACE inhibitors have also been utilized with some success.(Zheng et al. 2007) Other strategies include counseling, education and the exploration of social, financial and mental health issues that may be limiting compliance with medications.

Increase in BP during dialysis, or intradialytic hypertension, does not have a standard definition. Some studies defined it as increase in SBP > 10 mmHg from pre to post dialysis (Inrig et al. 2009). Intradialytic hypertension has been observed in 13 % of hemodialysis patients and has been associated with a higher risk of hospitalization and death than if BP decreases (Inrig et al. 2007b). In incident hemodialysis patients, intradialytic hypertension was associated with decreased 2 year survival in patients with predialysis SBP < 120 mmHg (Inrig et al. 2009). The pathogenesis of this phenomena is not well understood but some of the suggested mechanisms include altered balance of nitric oxide and endothelin-1, (Chou et al. 2006) removal of certain antihypertensives and administration of erythropoietin stimulating agents (Inrig 2010b). Treatment of this condition remains a challenge because its pathophysiology is not well understood. Any treatment strategy should include review of patient’s interdialytic BP control, dialysis sodium prescription, and dry weight. Additionally, a thorough review of the pharmacokinetics and timing of medications in relation to dialysis is needed. Carvedilol may have modest improvement in intradialytic and interdialytic BP control (Inrig et al. 2012). Another strategy is to use dialysate sodium concentration that is 5 mEq/L lower than serum sodium (Inrig et al. 2015).

In summary, hypertension is common among hemodialysis patients and its control is complicated by the limitations of various blood pressure measurement methods. The only published guidelines that include exact blood pressure goal is K/DOQI clinical practice guidelines, which recommend pre-dialysis BP < 140/90 mmHg and post dialysis < 130/80 mmHg (K/DOQI Workgroup 2005). However, given the evidence of U shape relationship between blood pressure and outcomes in hemodialysis patients, we recommend individualizing BP goals and relying on combination of average home readings, in-center readings and ambulatory blood pressure monitoring. When treating blood pressure in hemodialysis patients, non-pharmacological approach including sodium restriction, probing dry weight and lowering dialysate sodium, and pharmacological approach utilizing ACEI/ARB as first line therapy especially in patients with residual kidney function should be utilized. Intradialytic hypertension remains a challenging area to manage and require review of dialysis prescription and patient medications.