Sodium zirconium cyclosilicate (SZC), a potassium binder, rapidly corrects hyperkalemia and maintains normokalemia in patients with early and late stage chronic kidney disease (CKD), according to new study findings.
Of 751 CKD outpatients not receiving dialysis, 39% and 60% had a baseline estimated glomerular filtration rate (eGFR, mL/min/1.73 m2) of less than 30 or 30 or higher, respectively. Each received SZC 10 g three times daily for 24 to 72 hours for correction of hyperkalemia (defined as 5.1 mmol/L or higher), then SZC 5 g once daily (with dose titrations up to 15 g daily as needed) for up to 12 months as maintenance therapy. Most patients continued taking stable doses of renin-angiotensin-aldosterone system inhibitors, including mineralocorticoid receptor antagonists.
Overall, 82% of patients achieved normokalemia within 24 hours. Within 72 hours, 100% of patients with stage 4 to 5 CKD and 95% of patients with stage 1 to 3 CKD, had serum potassium values within normal range, Simon D. Roger, MD, of Renal Research in Australia and colleagues reported in Nephrology Dialysis Transplantation. In addition, 82% and 90% of patients, respectively, maintained normokalemia through day 365.
Serum bicarbonate levels also increased during treatment, possibly reducing the risk for metabolic acidosis and the need for alkali supplementation, according to the authors.
In the week after SZC discontinuation, serum potassium levels increased again in both groups, but remained below pre-treatment levels. “Thus, SZC therapy may have a potential safety window for patients missing doses of up to 1 week, during which time mean serum K+ would be expected to increase by 0.4–0.5mmol/L,” Dr Roger’s team wrote.
Adverse events were more common in the advanced CKD group, perhaps due in part to comorbidities and concomitant medications, according to the investigators. The top 3 adverse events in the advanced CKD group were hypertension (15%), peripheral edema (13%), and urinary tract infection (12%).
The investigators concluded that their analysis suggests that SZC corrects hyperkalemia and maintains normokalemia in outpatients with moderate to severe or end-stage CKD with similar efficacy to that observed in those with mild or moderate CKD or normal renal function, according to Dr Roger and his colleagues.
Disclosure: This study was supported by ZS Pharma, a subsidiary of AstraZeneca, which manufactures sodium zirconium cyclosilicate (Lokelma®). Please see the original reference for a full list of authors’ disclosures.
Roger SD, Lavin PT, Lerma EV, et al. Long-term safety and efficacy of sodium zirconium cyclosilicate for hyperkalaemia in patients with mild/moderate versus severe/end-stage chronic kidney disease: comparative results from an open-label, Phase 3 study [published online February 6, 2020]. Nephrol Dial Transplant 2020:1–14. doi: 10.1093/ndt/gfz285