Recipients of solid organ transplants commonly experience hyperkalemia, limiting use of pharmacotherapy in those patients. Hyperkalemia is associated with multifactorial causes, including kidney dysfunction, calcineurin inhibitor use, and infection prophylaxis. The effect of sodium zirconium cyclosilicate (SZ-9) on potassium in the general population has been studied; however, the impact of SZ-9 on immunosuppression in transplant recipients is unknown.
At the 2020 virtual American Transplant Congress, R. Winstead and colleagues reported results from a study designed to examine the effect of SZ-9 on potassium and tacrolimus levels in kidney, liver, and heart transplant recipients with hyperkalemia. The results were reported in a poster titled Sodium Zirconium Cyclosilicate Use in Solid Organ Transplant Recipients and its Effect on Potassium and Immunosuppression.
The researchers conducted a single center, retrospective medical record review of adult kidney, lover, and heart transplant recipients prior to and following initiation of ZS-9. Excluded patients initiated SZ-9 within 7 days of transplant or received the drug for fewer than 7 days. Patient evaluations were conducted at the time of diagnosis of hyperkalemia and 7 days after diagnosis.
Patients were expected to take SZ-9 two hours apart from other medications; dosing frequency ranged from once daily to three times daily. The primary outcome of interest was change in potassium from day 0 to day 7. Secondary outcomes were change in tacrolimus, sodium, and bicarbonate levels form day 0 to day 7, and any reported adverse effects. Characteristics and outcomes were assessed with both parametric and nonparametric statistical tests.
The analysis included records of 35 patients: 16 kidney transplant recipients, 14 liver transplant recipients, two heart transplant recipients, two combined kidney and liver transplant recipients, and one combined kidney and heart transplant recipient. Median time from transplant was 75 days.
Overall, nine patients initiated SZ-9 as an inpatient and 12 received three times a day dosing for severe hyperkalemia (mean potassium level, 6.2 mEq/L). The mean decrease in potassium from day 0 to day 7 was –1.3 mEq/L (P<.001) with a mean day 0 level of 5.9 mEq/L. Mean change in tacrolimus concentration was –0.54 ng/mL (P=.82). Mean change in sodium and bicarbonate concentrations from day 0 to day 7 were +1.70 mEq/L (P=.002) and +1.60 mEq/L (P=.006), respectively.
The most common reasons for discontinuation of SZ-9 were resolution of hyperkalemia due to improvement in renal function and/or discontinuation of sulfamethoxazole/trimethoprim. There were two reports of mild edema.
In conclusion, the researchers said, “SZ-9 successfully lowered the potassium level from day 0 to day 7 in transplant recipients on calcineurin inhibitors with no apparent significant impact on tacrolimus drug pharmacokinetics. Further studies are needed to study whether SZ-9 impacts other commonly used transplant medications such as mycophenolate.”
Source: Winstead R, Demehin M, Yakubu I, et al. Sodium zirconium cyclosilicate use in solid organ transplant recipients and its effect on potassium and immunosuppression. Abstract of a poster presented at the virtual American Transplant Congress (Abstract D-220), May 30, 2020.