Objective

Tacrolimus-mycophenolic acid (MPA)-prednisolone immunosuppression remains the first-line management of kidney transplantation. Despite this, a switch to low-dose tacrolimus in combination with an mTOR inhibitor may be inevitable in some patients due to various factors. This study aims to identify the reasons and factors influencing the switch of tacrolimus-MPA to other combination immunosuppressive agents among kidney transplant recipients (KTRs).

Methods

This retrospective observational cohort study included adult KTRs between year 2011-2019 at the two main kidney transplant centers in Malaysia. Demographic data, clinical, laboratory and medication information were collected. Multiple logistic regression was used to determine factors associated with the initial switch of tacrolimus-MPA immunosuppressive therapy.

Results

From the 257 KTRs studied, 81 KTRs had their immunosuppressive agents switched from tacrolimus-MPA-prednisolone immunosuppressive regimen, with majority (96.3%, n = 78) switching to everolimus, an mTOR inhibitor in combination with low-dose tacrolimus. The average time switch was 125.8 ± 100.9 days. The main reasons for the initial switch include unresolved transaminitis (n = 15, 18.5%), cytomegalovirus (CMV) infection (n = 13, 16.0%) and BK virus (BKV) infection (n = 10, 12.3%). In the multiple logistic analysis, Malay ethnicity (P < 0.001), KTRs without post-transplant hypertension (P = 0.004) and KTRs with BKV infection (P < 0.001) were predictors for the initial switch of tacrolimus-MPA-prednisolone immunosuppressive therapy.

Conclusion

Early identification of factors associated with the switch may prepare healthcare professionals for KTRs risk stratification, allowing ample time for appropriate optimization of tacrolimus-MPA-prednisolone immunosuppressive therapy based on individual patient's needs. This can possibly be a cost-effective alternative to switching to mTOR inhibitors for improved transplant outcomes.

Keywords

everolimus; immunosuppression switch; immunosuppressive agents; kidney transplantation; tacrolimus.

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