Study protocol for a prospective, multicenter, single-arm study investigating the impact of the implementation of standardized hyperkalemia management in chronic kidney disease patients.

BACKGROUND

Hyperkalemia (serum potassium > 5.0 mmol/L) is a common and clinically significant complication in patients with chronic kidney disease (CKD), particularly among those treated with renin-angiotensin-aldosterone system inhibitors (RAASi). Although guideline-directed medical therapy recommends proactive hyperkalemia management to enable continued RAASi use, real-world practice remains suboptimal. Key challenges include inadequate potassium monitoring after RAASi initiation or dose escalation, unnecessary RAASi dose reduction or discontinuation following hyperkalemia episodes, and poor long-term treatment adherence. Moreover, evidence regarding the cardio-renal benefits of RAASi optimization supported by structured hyperkalemia management in Chinese CKD populations is limited. This study aims to bridge the gap between Kidney Disease: Improving Global Outcomes (KDIGO) and Chinese CKD guideline recommendations and routine clinical practice through a nationwide quality improvement program (QIP).

METHODS

This prospective, multicenter, single-arm study will enroll approximately 1,000 adult Chinese patients with non-dialysis CKD and hyperkalemia across 50 sites. The QIP includes comprehensive and reinforcement training for healthcare professionals (HCPs) based on the KDIGO 2024 guidelines, supported by regular quality audits and feedback. Patient-directed interventions comprise structured education delivered by HCPs and self-learning modules. Participants will receive standardized hyperkalemia management over 96 weeks, including protocolized serum potassium monitoring (every 3 months or monthly for high-risk patients), RAASi dose optimization, and long-term potassium control. The primary endpoint is the proportion of patients achieving RAASi optimization with normokalemia (3.5-5.0 mmol/L) at 48 weeks. Secondary endpoints include sustained potassium control, RAASi optimization over time, medication adherence, hyperkalemia recurrence and severity, cardiorenal outcomes, and safety endpoints. DISCUSSION: As the first nationwide QIP focusing on hyperkalemia management in CKD patients in China, this study is expected to provide real-world evidence on the effectiveness of standardized hyperkalemia care in facilitating sustained RAASi use. By aligning clinical practice with guideline recommendations, the program has the potential to improve long-term cardio-renal outcomes and inform future CKD care strategies. TRIAL REGISTRATION: ClinicalTrials.gov, NCT06884267; registered March 13, 2025.