Kidney Week

Abstract: TH-PO1170

Sodium Zirconium Cyclosilicate (SZC) to Enable Renin Angiotensin-Aldosterone System Inhibitor (RAASi) Use for Diabetic Kidney Disease: The CRYSTAL Study

Session Information

• Late-Breaking Science Posters
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 702 Diabetic Kidney Disease: Clinical

Authors

• Wang, Weiming, Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, Shanghai, China

Weiming Wang, MD

• Gu, Leyi, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai, Shanghai, China

Leyi Gu, MD, PhD

• Zang, Xiujuan, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China

Xiujuan Zang, MD

• Liu, Na, Tongji University Dongfang Hospital, Shanghai, Shanghai, China

Na Liu, MD

• Pan, Yangbin, Shanghai Pudong Hospital, Shanghai, Shanghai, China

Yangbin Pan, PhD

• Jiang, Chunming, Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital, Nanjing, Jiangsu, China

Chunming Jiang, CNS

• Li, Ying, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai, China

Ying Li, MD

• Jiang, Gengru, Shanghai Jiaotong University School of Medicine Xinhua Hospital, Shanghai, China

Gengru Jiang, MD, DrPH

• Mao, Zhiguo, Shanghai Changzheng Hospital, Shanghai, China

Zhiguo Mao, MD, PhD

• Xue, Jun, Huashan Hospital Fudan University, Shanghai, Shanghai, China

Jun Xue, MD, PhD

• Zhou, Rong, Yangpu Hospital Affiliated to Tongji University School of Medicine, Shanghai, Shanghai, China

Rong Zhou, MD, PhD

• Xu, Hao, Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, Shanghai, China

Hao Xu

• Liu, Jian, Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, Shanghai, China

Jian Liu, MD

Background

RAASi, the preferred treatment for Diabetic Kidney Disease (DKD), can induce hyperkalemia, and reduction/discontinuation of RAASi will affect its cardio-renal benefits. This study evaluated the efficacy of SZC in maintaining RAASi use in stage 3–4 DKD patients.

Methods

This multicenter, open-label, randomized controlled, phase IV trial enrolled stage 3–4 DKD patients with hyperkalemia (sK >5.0 mmol/L) within 90 days prior to enrollment and randomized them 1:1 to SZC (SZC + RAASi) or control (RAASi-only) groups, with a 24-week follow-up (12-week RAASi titration + 12-week maintenance). The primary endpoint was the proportion of patients with increased RAASi dose by week 12.

Results

By June 28, 2024, this study included 86 patients in the intention-to-treat (ITT) set, and 56 adhered to study protocol (per-protocol, PP). The mean age of the ITT set was 58.7 years old, and 59.3% were male. Both ITT and PP analyses showed a significantly higher proportion of patients in the SZC group achieved increased dose of angiotensin-converting enzyme inhibitor (ACEi)/angiotensin II receptor blocker (ARB) than control at week 12 (ITT: 55.8% vs. 27.9%, p<0.05; PP: 71.4% vs. 28.6%, p<0.05; Figure 1). In the PP set, a higher proportion of the SZC group received ≥50% of the labeled maximum dose than control at weeks 12 (60.7% vs. 42.9%) and 24 (53.6% vs. 35.7%). From baseline to week 24, the SZC group had decreased mean UACR (-63.5 mg/g), whereas that in the control group increased (+316.9 mg/g). Adverse events occurred in 62.8% of the SZC group and 72.1% of the control group.

Conclusion

This study showed that using SZC to manage hyperkalemia can help optimize RAASi treatment for Chinese stage 3–4 CKD patients with diabetes and hyperkalemia. This can facilitate the use of RAASi at higher, guideline-recommended doses to achieve its cardio-renal benefits for DKD pts experiencing hyperkalemia.

Funding

• Commercial Support – AstraZeneca China