2025 Update on Resistant Hypertension in CKD: Where Do We Stand and Where Do We Go?

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Identified Weaknesses

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Paper Summary

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CKD's Stubborn BP: New Drugs and Denervation Offer Hope, But Watch Out for Side Effects and Sticker Shock!

This review summarizes current guidelines and emerging treatments for resistant hypertension in chronic kidney disease (CKD), advocating for individualized, evidence-based management. While novel agents and procedures show promise in blood pressure control and renal benefits, the paper highlights significant limitations, including adverse effects, poor long-term adherence, and high costs that may hinder their widespread use.

Possible Conflicts of Interest

None identified

Identified Weaknesses

Generalizability and methodological concerns of foundational trials

The paper notes that real-world applicability of some intensive blood pressure reduction targets, based on trials like SPRINT, is questioned due to reported variability in measurement protocols, affecting how reliably findings can be replicated in practice.

Inconclusive evidence for intensive BP control on overall renal outcomes

A comprehensive meta-analysis indicated that intensive blood pressure reduction did not show a significant overall advantage for kidney-related endpoints across all CKD stages, with benefits only borderline significant in specific, severe CKD subgroups.

Limited generalizability and adherence issues for spironolactone

Key trials for spironolactone in resistant hypertension excluded patients with more advanced CKD, limiting the direct applicability of findings to a significant portion of the CKD population. Additionally, real-world adherence is poor due to side effects like hyperkalemia and hormonal issues.

Significant adverse effects of chlorthalidone

The CLICK trial demonstrated a high incidence of adverse effects with chlorthalidone, including a substantial increase in serum creatinine in 45% of patients, alongside electrolyte imbalances (hypokalemia, hyponatremia) and dizziness.

Aprocitentan's side effects and cost

The dual endothelin receptor antagonist aprocitentan frequently caused fluid retention, which escalated with prolonged use and often necessitated diuretic adjustments. Its high cost is also identified as a significant barrier to broader clinical adoption.

Modest antihypertensive efficacy of some novel agents

Finerenone, while offering cardiorenal benefits, demonstrated only a modest 2-3 mmHg difference in systolic blood pressure compared to placebo in trials, suggesting its direct antihypertensive impact might be less pronounced than other agents.

Rating Explanation

This paper provides a thorough and balanced update on resistant hypertension in CKD, effectively synthesizing current guidelines and emerging treatments. It critically discusses both the benefits and significant limitations of various therapeutic options, making it a valuable resource for clinicians and researchers despite being a review rather than original research.

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