Real-world data back sodium zirconium cyclosilicate for hyperkalemia in HD patients

The novel potassium binder, sodium zirconium cyclosilicate, has proven to be safe and effective for lowering potassium levels in the blood of Asian patients undergoing maintenance haemodialysis (HD) treatments, as shown in a study from Singapore.

Real-world data from a cohort of chronic HD patients who received sodium zirconium cyclosilicate to either manage or prevent hyperkalaemia (ie, while travelling) showed that the use of the medication led to a 0.812-mmol/L reduction in serum potassium levels over the clinical audit period of 19 months. Potassium levels dropped to the normal range in 33.4 percent of the patients. [Cureus 2023;15:e45058]

The magnitude of reduction was consistent with that in clinical trials wherein treatment with sodium zirconium cyclosilicate resulted in a 0.46–1.28-mmol/L reduction in potassium levels within 48 hours. [ESC Heart Fail 2020;7:54-64; J Am Soc Nephrol 2019;30:1723-1733; N Engl J Med 2015;372:222-131; Clin J Am Soc Nephrol 2019;14:798-809]

However, the proportion of patients who achieved normal potassium levels after treatment with sodium zirconium cyclosilicate was lower than the 41.2–99.0 percent reported in the said trials. This difference, according to the investigators, might be attributed to the longer audit duration in the current study and the differences in patient population, with those receiving dialysis being excluded from the comparative trials. 

Not influenced by ethnicity

A total of 293 patients (median age 63.0 years) were included in the study, and 11 of them (3.8 percent) had dialysis vintage of 1 year or less. More than half of the patients were men (54.6 percent), of Chinese ethnicity (51.5 percent), and had diabetes mellitus as their primary diagnosis (50.9 percent). The mean sodium zirconium cyclosilicate treatment duration was 2.13 months, and the mean baseline serum potassium in patients treated for hyperkalaemia was 6.14 mmol/L. All patients with hyperkalaemia received their HD with a 2 mEq/L potassium dialysate. 

Serum potassium levels significantly decreased following sodium zirconium cyclosilicate treatment for patients of Chinese, Malay, and Indian ethnicities (mean change, –0.855, –1.01, –0.737 mmol/L, respectively; p<0.001 for all).

“This observation was consistent with findings from clinical trials which demonstrated that sodium zirconium cyclosilicate’s efficacy was not affected by age, gender, ethnicity, or comorbidity,” the investigators said. [J Am Soc Nephrol 2019;30:1723-1733; Kidney Int 2020,97:42-61]

Overall, sodium zirconium cyclosilicate was safe. Three gastrointestinal adverse events (AEs) related to treatment were recorded, namely diarrhoea, abdominal pain, and constipation. All AEs were considered mild, with none of the patients requiring immediate treatment or hospitalization.

Life-saving implications

“In addition to hyperkalaemia management, sodium zirconium cyclosilicate was also prescribed to patients travelling overseas for the prevention of hyperkalaemia. With missed or delayed dialysis sessions and increased risk of dietary noncompliance during travelling, is reasonable to assume that travelling patients may be at higher risk of hyperkalaemia-related morbidity and mortality,” according to the investigators.

The crude mortality rate among the travelling patients included in the study was 2.7 percent. None of the deaths were caused by hyperkalaemia, cardiac arrhythmias, or cardiac arrest. Additionally, none of the travelling patients reported AEs associated with sodium zirconium cyclosilicate use.

“This may suggest that a short course of sodium zirconium cyclosilicate is safe for chronic HD patients who plan to travel. Conversely, it can be argued that patients who can travel may be healthier than the overall chronic HD patient cohort, thus contributing to the observed low mortality rate,” the investigators said.

They called for additional studies to establish the effect of sodium zirconium cyclosilicate on reducing hyperkalaemia-related mortality among travelling HD patients.