Calcineurin inhibitors and the risk of preeclampsia in solid organ transplantation – Should we rethink our approach during pregnancy?

• Calcineurin inhibitors (CNIs), a cornerstone of immunosuppression in solid organ transplantation, causes endothelial dysfunction. • Endothelial dysfunction is a key shared mechanism in preeclampsia development and CNI toxicity. • Pregnancy alters tacrolimus pharmacokinetics, thus unbound tacrolimus levels may improve dosing precision and avoid toxicity. Preeclampsia is a significant cause of maternal and fetal morbidity and mortality worldwide. Characterized by the onset of hypertension and end organ dysfunction after 20 weeks of gestation, preeclampsia poses complex challenges, particularly in solid organ transplant (SOT) recipients who often have multiple comorbidities. Calcineurin inhibitors (CNIs) are the cornerstone of contemporary immunosuppression, but they are also associated with endothelial and vascular dysfunction − most commonly hypertension and nephrotoxicity − which may overlap with pathways implicated in the development of preeclampsia. This review synthesises clinical and mechanistic evidence relevant to CNI exposure and preeclampsia in SOTs. We also examine pregnancy related pharmacokinetic changes that lower measured whole blood tacrolimus concentrations and outline why reliance on trough targets alone can be misleading. Building on this evidence, we discuss a practical approach to tacrolimus dosing and monitoring during gestation, and highlight the need for accelerated development and validation of unbound tacrolimus measurement for routine clinical use in this population.