*Purpose: Transplant recipients often suffer from hyperkalemia which can limit pharmacotherapy. The cause of hyperkalemia is often multifactorial including kidney dysfunction, calcineurin inhibitor use, and infection prophylaxis. The purpose of this study is to describe effect of sodium zirconium cyclosilicate (ZS-9) on potassium (K+) and tacrolimus levels in kidney, liver, and heart transplant recipients with hyperkalemia. While the effect of ZS-9 on K+ has been shown in the general population, the impact it may have on immunosuppression has not been described.

*Methods: This was a single center, retrospective medical record review of adult kidney, liver, and heart transplant recipients before and after initiation of ZS-9. Patients were excluded if they began the drug within 7 days of transplant or received the drug for less than 7 days. Patients were evaluated at the time of hyperkalemia diagnosis and 7 days later. Patients were instructed to take the drug two hours apart from other medications, and the dosing frequency ranged from daily to three times daily. The primary outcome was the change in potassium from day 0 to day 7. Secondary outcomes included change in tacrolimus, sodium, and bicarbonate levels from day 0 to day 7 and any reported adverse effects. Descriptive statistics; both parametric and nonparametric statistical tests were used to assess characteristics and outcomes.

*Results: 35 patients were included in the analysis: 16 kidneys (45.7%), 14 livers (40%), 2 hearts (5.7%), 2 combined kidney and liver transplant recipients (5.7%), and 1 combined kidney and heart transplant recipient (2.9%). The median time from transplant was 75 days. Overall, 9 (26%) patients initiated ZS-9 as an inpatient, and 12 (34%) patients received TID dosing for severe hyperkalemia for a mean K+ of 6.2 (SD = 0.39). The mean decrease in K+ from day 0 to day 7 was -1.3 mEq/L, p-value = <0.001 (SD = 0.75) with a mean day 0 level of 5.9 mEq/L (SD = 0.47). The mean change in tacrolimus concentrations was -0.54 ng/mL, p-value = 0.82 (SD = 3.31). The mean change in sodium and bicarbonate concentrations respectively, from days 0 to day 7 was +1.70 mEq/L, p-value = 0.002 (SD = 3.12) and +1.60 mEq/L, p-value 0.006 (SD = 3.57). The most common reasons for discontinuation of ZS-9 were resolution in hyperkalemia due to improvement in renal function and/or discontinuation of sulfamethoxazole/trimethoprim. There were two reports of mild edema.

*Conclusions: ZS-9 successfully lowered the K+ 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 ZS-9 impacts other commonly used transplant medications such as mycophenolate.

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