Management of Hypertension in Advanced Kidney Disease

Abstract and Introduction

Abstract

Purpose of Review: The aim of this study was to present recent developments in pharmacotherapy of hypertension in patients with advanced chronic kidney disease (CKD).

Recent Findings: In the AMBER trial, compared with placebo, the potassium-binder patiromer mitigated the risk of hyperkalaemia and enabled more patients with uncontrolled resistant hypertension and stage 3b/4 CKD to tolerate and continue spironolactone treatment; add-on therapy with spironolactone provoked a clinically meaningful reduction of 11–12 mmHg in unattended automated office SBP over 12 weeks of follow-up. In the BLOCK-CKD trial, the investigational nonsteroidal mineralocorticoid-receptor-antagonist (MRA) KBP-5074 lowered office SBP by 7–10 mmHg relative to placebo at 84 days with a minimal risk of hyperkalaemia in patients with advanced CKD and uncontrolled hypertension. The CLICK trial showed that the thiazide-like diuretic chlorthalidone provoked a placebo-subtracted reduction of 10.5 mmHg in 24-h ambulatory SBP at 12 weeks in patients with stage 4 CKD and poorly controlled hypertension.

Summary: Enablement of more persistent spironolactone use with newer potassium-binding agents, the clinical development of novel nonsteroidal MRAs with a more favourable benefit-risk profile and the recently proven blood pressure lowering action of chlorthalidone are three therapeutic opportunities for more effective management of hypertension in high-risk patients with advanced CKD.

Introduction

Hypertension is the most common comorbidity in patients with chronic kidney disease (CKD) and it can be either the cause or a consequence of kidney damage.^[1] The burden of hypertension travels hand-in-hand with the severity of CKD,^[2] with an increasing prevalence of high blood pressure (BP) from 67% in patients with preserved kidney function up to 92% in those with an estimated glomerular filtration rate (eGFR) less than 30 ml/min/1.73 m².^[3] Furthermore, independent of eGFR, albuminuria is directly associated with the severity of hypertension.^[4,5] Compared with those without CKD, despite the more aggressive treatment of hypertension in patients with advanced CKD, BP often remains inadequately controlled.^[6] The prevalence of resistant hypertension, defined as uncontrolled BP despite treatment with three antihypertensives in optimal doses that include a diuretic, is two to three times higher in stage 3b/4 CKD than in the general population.^[7–9] Compared with controlled hypertension, true resistance to antihypertensive treatment is associated with an increased risk for adverse cardiovascular events and incident kidney failure.^[10,11] There is therefore a critical unmet need for more effective BP control in this high-risk patient population.

The purpose of this article is to present recent developments in the field of pharmacotherapy of hypertension in advanced CKD. We discuss evidence from recently completed randomized trials and provide directions for future research in this important scientific area.