Despite hemodialysis, patients with end-stage renal disease frequently experience predialysis hyperkalemia. The DIALIZE trial (NCT03303521), a phase 3b, randomized, double-blind, placebo-controlled trial, investigated the effect of sodium zirconium cyclosilicate (SZC) on predialysis serum potassium after the long interdialytic interval in dialysis patients with hyperkalemia. Several post hoc analyses of DIALIZE data have been conducted.
The DIALIZE trial included a total of 196 patients. Mean age was 58.1 years. The patients were randomized 1:1 to receive placebo (n=99) or SZC (n=97) 5 mg once daily starting dose on nondialysis days for 8 weeks: a 4-week SZC dose-titration phase [maximum, 15 g] to achieve target predialysis serum potassium 4.0 to 5.0 mmol/L and a 4-week stable-dose evaluation phase (SZC 0, 5, 10, or 15 g).
Post hoc analyses of DIALIZE data included assessment of the number of visits where patients had serum potassium of 4–5 mmol/L and 3.5–5.5 mmol/L, as well as the maximum serum potassium during the evaluation phase. Cross tabulation of categorized change in potassium gradient from baseline to end of the evaluation phase was also assessed. The change in potassium gradient was defined as the difference between the predialysis serum potassium and dialysate potassium.
Rapid lowering of serum potassium is permitted with a high serum potassium to difference in potassium gradient at the start of hemodialysis. However, there can be an association between rapid serum potassium lowering and an increased risk of adverse events, such as cardiac arrhythmias and hospitalization.
There was an association between SZC and more patients achieving serum potassium 4.0 to 5.0 mmol/L and being maintained as serum potassium 3.5 to 5.5 mmol/L versus placebo for one, two, three, and four visits. During the evaluation period, 56 patients in the placebo group had severe predialysis hyperkalemia (defined as serum potassium ≥6 mmol/L) compared with only 14 in the SZC group.
In the SZC group there was a shift in potassium gradient toward values below the reported higher risk threshold of 3 mmol/L: 30.6% of patients (n=11/36) moved from gradient 4–5 to 2–3 mmol/L and 55.6% (n=25/45) moved from 3–4 to 2–3 mmol/L.
In conclusion, the researchers said, “These findings suggest that treatment with SZC improves management and reduces the frequency of severe hyperkalemia in hemodialysis patients, which could potentially modify the risks association with these factors.”
Source: Fishbane S, Al-shurbaji A, Guzman N, et al. Sodium zirconium cyclosilicate (SZC) improves potassium balance in hyperkalemic hemodialysis patients: Results from the phase 3b, randomized, placebo-controlled DIALIZE study. Abstract of a presentation at the American Society of Nephrology Kidney Week 2019 (Abstract SA-OR061), November 9, 2019, Washington, DC.