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Resistant Hypertension in Chronic Kidney Disease (CKD): Prevalence, Treatment Particularities, and Research Agenda

  • Resistant Hypertension (L Drager, Section Editor)
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Abstract

Purpose of Review

To explore the prevalence, treatment particularities, and research agenda in the management of resistant hypertension among patients with chronic kidney disease (CKD).

Recent Findings

The prevalence of resistant hypertension is reported to be 2–3 times higher in patients with CKD than in the general hypertensive population. Based in part on the results of the PATHWAY-2 trial showing add-on spironolactone to be superior to placebo or active treatment with an α- or β-blocker in reducing BP, international guidelines recommend the use of spironolactone as fourth-line agent in pharmacotherapy of resistant hypertension. Despite the several-fold higher burden of resistant hypertension among patients with stage 3b–4 CKD, the use of spironolactone in this population has been restricted, mainly due to the risk of hyperkalemia. The recently reported AMBER trial showed that among patients with uncontrolled resistant hypertension and an estimated glomerular filtration rate of 25–45 ml/min/1.73m2, the newer potassium-binder patiromer prevented the development of hyperkalemia and increased the proportion of participants who remained on add-on spironolactone over 12 weeks of follow-up. Administration of spironolactone was associated with a clinically meaningful reduction of 11–12 mmHg in unattended automated office systolic blood pressure (BP) over the course of the AMBER trial.

Summary

Newer potassium-binding therapies overcome the barrier of hyperkalemia and facilitate the persistent use of spironolactone, which is an effective add-on therapy to control BP in patients with resistant hypertension and advanced CKD. Future trials are now warranted to explore whether this strategy confers benefits on “hard” clinical outcomes in this high-risk population.

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Financial Information

RA is supported by NIH 5 R01 HL126903-02 and a grant from VA Merit Review 5I01CX000829-04.

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Authors and Affiliations

  1. Section of Nephrology and Hypertension, 1st Department of Medicine, AHEPA Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece

    Panagiotis I. Georgianos

  2. Division of Nephrology, Department of Medicine, Indiana University School of Medicine and Richard L. Roudebush Veterans Administration Medical Center, 1481 West 10th Street, Indianapolis, IN, USA

    Rajiv Agarwal

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  1. Panagiotis I. Georgianos
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Contributions

Review concept and design: both authors.

Literature review, analysis, and interpretation of data: both authors.

Drafting of the initial version of the manuscript: PIG.

Critical revision of the manuscript for important intellectual content: RA.

Corresponding author

Correspondence to Rajiv Agarwal.

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Conflict of Interest

RA has the following disclosures outside the focus of this article: Member data safety monitoring committees: Astra Zeneca, Ironwood Pharmaceuticals. Member steering committees of randomized trials: Akebia, Bayer, Janssen, Glaxo Smith Cline, Relypsa, Sanofi and Genzyme US Companies; Member adjudication committees: Bayer, Boehringer Ingelheim, Janssen; Member scientific advisory board or consultant: Celgene, Daiichi Sankyo, Inc., Eli Lilly, Relypsa, Reata, Takeda Pharmaceuticals, USA, ZS Pharma.

PIG has nothing to disclose.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Resistant Hypertension

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Georgianos, P.I., Agarwal, R. Resistant Hypertension in Chronic Kidney Disease (CKD): Prevalence, Treatment Particularities, and Research Agenda. Curr Hypertens Rep 22, 84 (2020). https://doi.org/10.1007/s11906-020-01081-x

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