Work

Sodium Zirconium Cyclosilicate in CKD, Hyperkalemia, and Metabolic Acidosis

Year: 2024

Type: article

Abstract: Key Points Sodium zirconium cyclosilicate effectively lowers serum potassium and maintains normokalemia in patients with CKD with concomitant hyperkalemia and metabolic acidosis. Despite high screen failure and small sample size, a nominally significant increase in sHCO 3 – was seen for sodium zirconium cyclosilicate versus placebo. Further studies on the basis of an appropriate cohort size may help validate the trend observed in sHCO 3 – levels, supporting these clinically relevant findings. Background Metabolic acidosis and hyperkalemia are common in CKD. A potential dual effect of sodium zirconium cyclosilicate (SZC), a selective binder of potassium in the gastrointestinal tract, on serum potassium (sK + ) and serum bicarbonate (sHCO 3 − ) was evaluated in patients with hyperkalemia and metabolic acidosis associated with CKD. Methods In the NEUTRALIZE study (NCT04727528), non-dialysis patients with stage 3–5 CKD, hyperkalemia (sK + >5.0 to ≤5.9 mmol/L), and metabolic acidosis (sHCO 3 − 16–20 mmol/L) received open-label SZC 10 g three times daily for ≤48 hours. Patients achieving normokalemia (sK + 3.5–5.0 mmol/L) were randomized 1:1 to SZC 10 g or placebo daily for 4 weeks. The primary end point was patients (%) maintaining normokalemia at the end of treatment (EOT) without rescue. Secondary end points included mean change in sHCO 3 − at EOT (day 29) and patients (%) with normokalemia with a ≥3-mmol/L increase in sHCO 3 − without rescue. Results Of 229 patients screened, 37 were randomized (SZC, n =17; placebo, n =20). High screen failure led to early study termination. At EOT, 88.2% (SZC) versus 20.0% (placebo) of patients maintained normokalemia (odds ratio, 56.2; P = 0.001). Low enrollment rendered secondary end point P values nominal. SZC treatment provided nominally significant increases in sHCO 3 – versus placebo from day 15 onward. Patients with normokalemia with a ≥3-mmol/L increase in sHCO 3 − without rescue were 35.3% (SZC) and 5.0% (placebo; P < 0.05). No new safety concerns were reported. Conclusions SZC effectively lowered sK + and maintained normokalemia, with nominally significant increases in sHCO 3 – observed for SZC versus placebo.

Source: Kidney360

DOI: 10.34067/kid.0000000000000446