Abstract
BackgroundOral sodium zirconium cyclosilicate (SZC) is a novel potassium binder capable of achieving a rapid reduction of serum potassium (sK+) and maintaining a long-term normokalemia. We undertook a meta-analysis to summarize and evaluate the effects surrounding SZC in patients with hyperkalemia.MethodWe searched data sources from MEDLINE (from 1950 to Sep 2020), EMBASE (from 1970 to Sep 2020), and the Cochrane Library database (from 1950 to Sep 2020) for eligible studies. All randomized controlled trials (RCTs) regarding comparison of therapeutic effects of SZC in hyperkalemia participants were included.ResultsSeven studies, including 1697 patients with hyperkalemia, were analyzed. SZC significantly reduced mean sK+ (−0.42 mmol/L; 95% CI: −0.63 to −0.20 mmol/L, p = 0.0001) compared with placebo, with a significantly greater proportion of patients with normokalemia (RR 3.48, 95% CI 1.49 to 8.11, p = 0.004). Subgroup analyses showed that the longer durations of SZC treatment, the greater magnitudes of potassium reduction when compared with those of placebo (p between subgroups = 0.01) at correction phase. Besides, it also demonstrated sK+ tended to decrease more in patients who got longer treatment or larger dosage of SZC at maintenance phase; however, the difference did not reach statistical significance. Additionally, the drug was equally effective in studies with larger than 50% of patients with chronic kidney disease (CKD) or diabetes or patients using renin-angiotensin aldosterone system inhibitor (RAAS) inhibitors (all p < 0.05). The risk of edema (4.30, 1.17 to 15.84; p = 0.03) in SZC group was higher than those of placebo group. No statistically significant differences in the risks of other adverse events were observed between the two groups.ConclusionsSZC effectively decreased the sK+ level in patients with hyperkalemia within 48 h and had benefits in the long-term control of serum potassium in patients who continued to receive SZC with a favorable safety profile from available data.
Highlights
Hyperkalemia is a common electrolyte disorder that can cause potentially life-threatening arrhythmias [1]
The benefit of RAASi treatment in heart and kidney diseases is limited by some side effects, such as increased sK+, which is especially severe in patients with renal insufficiency [6]
Baseline characteristics of patients in trials were estimated, and the results showed that the mean age was 65 ± 13 years, the mean serum potassium was 5.3 ± 0.8 mmol/L, and the mean weight was 83.7 ± 22.4 kg
Summary
Hyperkalemia is a common electrolyte disorder that can cause potentially life-threatening arrhythmias [1]. An increased risk of hyperkalemia was observed in patients with chronic kidney disease (CKD, 22.8%) [2], heart failure (HF, 13.4%), diabetes (10.8%), and renin-angiotensin-aldosterone system inhibitor (RAASi, 14.2%) use [3–5]. The benefit of RAASi treatment in heart and kidney diseases is limited by some side effects, such as increased sK+, which is especially severe in patients with renal insufficiency [6]. It is worth noting that after the first hyperkalemia attack, 53.7 or 13.1% of patients experienced RAASi withdrawal or dose reduction, respectively [2]. Some observational cohorts suggested that hyperkalemia was associated with reduction or cessation of RAAS inhibitors [7–9]. The occurrence of hyperkalemia in CKD patients is closely related to the poor prognosis [2]. We undertook a meta-analysis to summarize and evaluate the effects surrounding SZC in patients with hyperkalemia. All randomized controlled trials (RCTs) regarding comparison of therapeutic effects of SZC in hyperkalemia participants were included
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