Kidney Week

Abstract: SA-PO0541

Randomized Controlled Trial of Thiazide Diuretics, Calcium Polystyrene Sulfonate, and Sodium Zirconium Cyclosilicate for Hyperkalemia in CKD

Session Information

• CKD: Clinical - Therapies, CKM Health, Special Populations, and More
  October 24, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2202 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

• Kittrakulrat, Jathurong, Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand

Jathurong Kittrakulrat, MD

• Phannajit, Jeerath, Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand

Jeerath Phannajit, MD

• Udomkarnjananun, Suwasin, Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand

Suwasin Udomkarnjananun, MD

• Wuttiputhanun, Thunyatorn, Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand

Thunyatorn Wuttiputhanun

• Tungsanga, Somkanya, Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand

Somkanya Tungsanga, MD, PhD

• Takkavatakarn, Kullaya, Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand

Kullaya Takkavatakarn, MD, PhD

• Tiranathanagul, Khajohn, Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand

Khajohn Tiranathanagul, MD

• Eiam-Ong, Somchai, Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand

Somchai Eiam-Ong, MD

• Avihingsanon, Yingyos, Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand

Yingyos Avihingsanon, MD

• Leelahavanichkul, Asada, Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand

Asada Leelahavanichkul, MD

• Townamchai, Natavudh, Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand

Natavudh Townamchai, MD

Background

Hyperkalemia is a common complication of chronic kidney disease (CKD). Although KDIGO recommends diuretics or potassium binders, no class is preferred due to the lack of head-to-head trials. We compared the efficacy, safety, and metabolic effects of sodium zirconium cyclosilicate (SZC), calcium polystyrene sulfonate (CPS), and hydrochlorothiazide (HCTZ) in CKD.

Methods

We conducted a randomized, open-label, active-controlled trial in adults with non-dialysis CKD (eGFR <60 mL/min/1.73 m²) and non–life-threatening hyperkalemia (serum potassium 4.8–5.9 mmol/L). Participants were randomized (1:1:1) to SZC 5 g/day, CPS 10 g/day, or HCTZ 25 mg/day for 14 days. The primary outcome was change in serum potassium at Day 7. Secondary outcomes included kidney function, acid–base status, blood pressure, and tolerability. Analyses used linear mixed-effects models.

Results

Eighty-four participants were randomized (mean eGFR 31.96±14.12 mL/min/1.73 m²; serum potassium 5.05±0.26 mmol/L). All treatments significantly reduced potassium at Day 7 with no between-group differences (LS mean change: SZC −0.44, CPS −0.44, HCTZ −0.40 mmol/L; P=0.91), with sustained effects at Day 14. Despite similar efficacy, treatment-specific physiological profiles were observed. HCTZ resulted in a significant decline in eGFR at Day 7 (−3.26 vs −0.43 CPS vs +2.50 SZC mL/min/1.73 m²; P<0.001) and increased BUN/creatinine ratio, consistent with hemodynamic kidney effects. HCTZ also significantly reduced systolic blood pressure within-group at Day 7 (−5.03 mmHg; 95% CI −9.89 to −0.18; P=0.042). In contrast, SZC significantly increased serum bicarbonate within-group at Day 7 (+0.85 mmol/L; 95% CI 0.08–1.63; P=0.032) and Day 14 (+1.55 mmol/L; 95% CI 0.18–2.92; P=0.026), with stable kidney function. CPS was associated with more frequent constipation (18.5%). Treatment palatability favored HCTZ.

Conclusion

In CKD, SZC, CPS, and HCTZ achieve comparable short-term potassium reduction, but differ meaningfully in kidney hemodynamics, acid–base effects, and tolerability. HCTZ lowers blood pressure at the cost of reversible kidney function decline, whereas SZC provides concurrent correction of metabolic acidosis with favorable kidney safety. These findings support a phenotype-guided approach to hyperkalemia management rather than a uniform strategy.

Acknowledgment

This study was supported by the Ratchadapisek Sompoch Endowment Fund, Faculty of Medicine, Chulalongkorn University.

Funding

• Government Support – Non-U.S.