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Treatment of Hypertension in Light of the New Guidelines: Pharmacologic Approaches Using Combination Therapies

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Resistant Hypertension in Chronic Kidney Disease

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Abstract

There is very little evidence to guide the pharmacological therapy of resistant hypertension (RH) in patients with advanced chronic kidney disease (CKD), since these patients have usually been excluded from randomized controlled trials (RCTs) in hypertension. Combined therapy, however, has to be individualized, depending on the patient’s pathophysiologic profile, comorbidities, and contraindications. The optimal combination should be well tolerated, and antihypertensive agents should be chosen after consideration of their metabolism and dosing adjustments according to the renal function.

In patients requiring a triple therapy, this should consist of an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) + a calcium channel blocker (CCB) + a diuretic (the ACD regimen) for most patients. This recommendation is based on studies in the general population; however, the ACD regimen is thought to be effective and well tolerated in CKD. The ACEIs and ARBs are especially preferred in patients with CKD and heart failure, post-myocardial infarction, or proteinuria. However, in patients with pre-dialysis CKD stages 4 and 5, ACEIs/ARBs should be avoided or used with great care, especially when there is high risk of hyperkalemia and/or acute kidney injury. Dual therapy ACEI + ARB or ACEI/ARB + direct renin inhibitor (DRI) is not indicated, because of increased risk of adverse events and lack of proven benefits. In patients with RH, diuretic therapy should be reinforced, together with salt restriction. In those with CKD stage 4 or with significant edema, thiazide diuretics should be replaced or combined with loop diuretics. CCBs are particularly useful in hypertensive patients who also have angina and/or supraventricular arrhythmia.

Mineralocorticoid receptor (MR) antagonists may be used as fourth-line therapy for RH in patients with GFR ≥30 ml/min and plasma potassium concentrations ≤4–5 mmol/l or in those with associated heart failure. However, these drugs should be used with caution in CKD, particularly in combination with ACEIs or ARBs, because of increased risk of hyperkalemia and acute kidney injury. Beta-blockers (BBs) have been widely used to treat hypertension, as well as coronary artery disease, heart failure, and cardiac arrhythmias. Agents like metoprolol and carvedilol should be preferred over atenolol, which may accumulate in patients with CKD. Other fourth- or fifth-line antihypertensive agents include centrally acting alpha-agonists, alpha-blockers, and direct vasodilators. These are potent blood pressure-lowering drugs, but their use is limited by numerous potential side effects.

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  1. Nefrocare MS Dialysis Centre, Iaşi, Romania

    Liviu Segall

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  1. Liviu Segall
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  1. Grigore T. Popa University of Medicine, Iaşi, Romania

    Adrian Covic

  2. Department of Medicine, Division of Nephrology, University School of Medicine, Istanbul, Turkey

    Mehmet Kanbay

  3. Section of Nephrology, University of Illinois at Chicago College of Medicine/Advocate Christ Medical Center, Oak Lawn, Illinois, USA

    Edgar V. Lerma

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Segall, L. (2017). Treatment of Hypertension in Light of the New Guidelines: Pharmacologic Approaches Using Combination Therapies. In: Covic, A., Kanbay, M., Lerma, E. (eds) Resistant Hypertension in Chronic Kidney Disease. Springer, Cham. https://doi.org/10.1007/978-3-319-56827-0_18

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