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      Pharmacotherapy of Hypertension in Chronic Dialysis Patients

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          Abstract

          Among patients on dialysis, hypertension is highly prevalent and contributes to the high burden of cardiovascular morbidity and mortality. Strict volume control via sodium restriction and probing of dry weight are first-line approaches for the treatment of hypertension in this population; however, antihypertensive drug therapy is often needed to control BP. Few trials compare head-to-head the superiority of one antihypertensive drug class over another with respect to improving BP control or altering cardiovascular outcomes; accordingly, selection of the appropriate antihypertensive regimen should be individualized. To individualize therapy, consideration should be given to intra- and interdialytic pharmacokinetics, effect on cardiovascular reflexes, ability to treat comorbid illnesses, and adverse effect profile. β-Blockers followed by dihydropyridine calcium-channel blockers are our first- and second-line choices for antihypertensive drug use. Angiotensin–converting enzyme inhibitors and angiotensin receptor blockers seem to be reasonable third–line choices, because the evidence base to support their use in patients on dialysis is sparse. Add-on therapy with mineralocorticoid receptor antagonists in specific subgroups of patients on dialysis ( i.e., those with severe congestive heart failure) seems to be another promising option in anticipation of the ongoing trials evaluating their efficacy and safety. Adequately powered, multicenter, randomized trials evaluating hard cardiovascular end points are urgently warranted to elucidate the comparative effectiveness of antihypertensive drug classes in patients on dialysis. In this review, we provide an overview of the randomized evidence on pharmacotherapy of hypertension in patients on dialysis, and we conclude with suggestions for future research to address critical gaps in this important area.

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          Prevalence, treatment, and control of hypertension in chronic hemodialysis patients in the United States.

          Hypertension is common in chronic hemodialysis patients, yet there are limited data on the epidemiology of hypertension in these patients in the United States. We assessed the prevalence, treatment, and control of hypertension in a cohort of 2535 clinically stable, adult hemodialysis patients who participated in a multicenter study of the safety and tolerability of an intravenous iron preparation. Hypertension was defined as an average predialysis systolic blood pressure >150 mm Hg or diastolic blood pressure >85 mm Hg, or the use of antihypertensive medications. Hypertension was documented in 86% (n = 2173) of patients. The prevalence of hypertension, in contrast to that observed in the general population, did not increase linearly with age and was not affected by sex or ethnicity. Hypertension was controlled adequately in only 30% (n = 659) of the hypertensive patients. In the remaining patients, hypertension was either untreated (12% [252/2173]) or treated inadequately (58% [1262/2173]). Control of hypertension, particularly systolic hypertension, in chronic hemodialysis patients in the United States is inadequate, despite recognition of its prevalence and the frequent use of antihypertensive drugs. Optimizing the use of medications and closer attention to nonpharmacologic interventions, such as adjustment of dry weight, a low-sodium diet, and exercise, may improve control.
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            Left ventricular mass monitoring in the follow-up of dialysis patients: prognostic value of left ventricular hypertrophy progression.

            Regression of left ventricular hypertrophy (LVH) in the setting of a well-planned intervention study has been associated with longer survival in hemodialysis patients. Whether changes in left ventricular mass (LVM) in clinical practice predict survival and cardiovascular events in these patients is still unknown. In a prospective study in 161 hemodialysis patients we tested the prognostic value of changes in LVM on survival and incident cardiovascular events. Echocardiography was performed twice, 18 +/- 2 SD months apart. Changes in LVM occurring between the first and the second echocardiographic study were then used to predict mortality and cardiovascular events during the ensuing 29 +/- 13 months. The prognostic value of LVM changes was tested in a multivariate Cox's model with LVM index (LVMI) [expressed as LVM/height(2.71)], included as a covariate to control for regression to the mean. The rate of increase of LVMI was significantly (P= 0.029) higher in patients with incident cardiovascular events than in those without such events. Accordingly, cardiovascular event-free survival in patients with changes in LVMI below the 25th percentile was significantly (P= 0.004) higher than in those with changes above the 75th percentile. In a multiple Cox regression analysis, including age, diabetes, smoking, homocysteine, 1 g/m(2.7)/month increase in LVMI was associated with a 62% increase in the incident risk of fatal and nonfatal cardiovascular events [hazard ratio 1.62 (95% CI 1.13-2.33), P= 0.009]. Changes in LVMI have an independent prognostic value for cardiovascular events and provide scientific support to the use of repeated echocardiographic studies for monitoring cardiovascular risk in dialysis patients.
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              Dry-weight reduction in hypertensive hemodialysis patients (DRIP): a randomized, controlled trial.

              Volume excess is thought to be important in the pathogenesis of hypertension among hemodialysis patients. To determine whether additional volume reduction will result in improvement in blood pressure (BP) among hypertensive patients on hemodialysis and to evaluate the time course of this response, we randomly assigned long-term hypertensive hemodialysis patients to ultrafiltration or control groups. The additional ultrafiltration group (n=100) had the dry weight probed without increasing time or duration of dialysis, whereas the control group (n=50) only had physician visits. The primary outcome was change in systolic interdialytic ambulatory BP. Postdialysis weight was reduced by 0.9 kg at 4 weeks and resulted in -6.9 mm Hg (95% CI: -12.4 to -1.3 mm Hg; P=0.016) change in systolic BP and -3.1 mm Hg (95% CI: -6.2 to -0.02 mm Hg; P=0.048) change in diastolic BP. At 8 weeks, dry weight was reduced 1 kg, systolic BP changed -6.6 mm Hg (95% CI: -12.2 to -1.0 mm Hg; P=0.021), and diastolic BP changed -3.3 mm Hg (95% CI: -6.4 to -0.2 mm Hg; P=0.037) from baseline. The Mantel-Hanzel combined odds ratio for systolic BP reduction of > or =10 mm Hg was 2.24 (95% CI: 1.32 to 3.81; P=0.003). There was no deterioration seen in any domain of the kidney disease quality of life health survey despite an increase in intradialytic signs and symptoms of hypotension. The reduction of dry weight is a simple, efficacious, and well-tolerated maneuver to improve BP control in hypertensive hemodialysis patients. Long-term control of BP will depend on continued assessment and maintenance of dry weight.
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                Author and article information

                Journal
                Clin J Am Soc Nephrol
                Clin J Am Soc Nephrol
                clinjasn
                cjn
                CJASN
                Clinical Journal of the American Society of Nephrology : CJASN
                American Society of Nephrology
                1555-9041
                1555-905X
                7 November 2016
                24 October 2016
                : 11
                : 11
                : 2062-2075
                Affiliations
                [* ]Division of Nephrology and Hypertension, First Department of Medicine, AHEPA Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece;
                []Department of Medicine, Indiana University School of Medicine, Indianapolis, Indianapolis; and
                []Division of Nephrology, Department of Medicine, Richard L. Roudebush Veterans Administration Medical Center, Indianapolis, Indianapolis
                Author notes
                Correspondence: Prof. Rajiv Agarwal, Department of Medicine, Indiana University School of Medicine and Richard L. Roudebush Veterans Administration Medical Center, 1481 West 10th Street, Indianapolis, IN 46202. Email: ragarwal@ 123456iu.edu
                Article
                PMC5108184 PMC5108184 5108184 00870116
                10.2215/CJN.00870116
                5108184
                27797886
                bd6942d4-89e7-4259-a123-03b74112a0e4
                Copyright © 2016 by the American Society of Nephrology
                History
                Page count
                Figures: 0, Tables: 6, Equations: 0, References: 77, Pages: 14
                Categories
                Evidence-Based Nephrology
                Custom metadata
                November 07, 2016

                hypertension,Sodium,renal dialysis,Mineralocorticoid Receptor Antagonists,Humans,blood pressure,Antihypertensive Agents,Angiotensin-Converting Enzyme Inhibitors,Angiotensin Receptor Antagonists,Adrenergic beta-Antagonists,cardiovascular disease,pharmacotherapy

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