Exceptional High Dose Tacrolimus Requirement in a Twin pregnancy Post Kidney Transplant: Review and Case Report

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Abstract

Introduction

An improvement in fertility after kidney transplant is considered one of the major benefits. Calcineurin inhibitors (CNI) including tacrolimus and cyclosporine are safe during pregnancy. CNIs cross the placenta and enter the fetal circulation. Variability in the pharmacokinetics of the tacrolimus level in pregnancy has been reported, and data on twin pregnancy is limited. Case Report: We report a 32 year old female with renal failure of unknown etiology, status post living related kidney transplant 2 years ago. She was on Tacrolimus 2mg BID, Mycophenolate mofetil (MMF) 500mg BID which was switched to Azathioprine 100 mg daily upon pregnancy. Her baseline creatinine (Cr) was 60 μmol/L and tacrolimus level in the range of 5.5. She was seen in her first trimester with dichoroinic amniotic twin pregnancy, post invetro fertilization. Laboratory results revealed Cr of 54 μmol/L and tacrolimus level of 2.4, subsequently the tacrolimus dose increased by 3 folds to 12mg daily to achieve a level of 5.3 after 8 weeks. Her Cr was 71 and ultrasound of both twins was normal. Area under the curve (AUC) calculated by wong equation 107 ng/h/ml by armendaris 103 ng/h/ml which considered therapeutic. She delivered without fetal or maternal complication.

Conclusion

Tacrolimus can be considered a valuable option during pregnancy although the variability in its level still exists. It appears from our case that twin pregnancy can impact the metabolism of tacrolimus. Accordingly, frequent monitoring of renal function and whole blood level with unbound trough concentrations of tacrolimus is required to ensure better maternal and neonatal outcome. Further pharmacokinetic studies can better explain the effect of pregnancy on tacrolimus dosing.

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