Background: Tacrolimus is an immunosuppressive agent that is prescribed to prevent acute rejection following solid organ transplantation such as kidney, liver, and heart transplantations. It is widely used agent, however, characterized by narrow therapeutic index and high inter-individual variability in dose requirement necessitating frequent therapeutic drug monitoring to prevent acute rejection or renal toxicity. The primary mechanism by which Calcineurin Inhibitors (CNIs) depress the immune system is by impairing the T helper cell's calcineurin-Nuclear Factor of Activated T cells (NFAT) signaling pathway. Individual differences exist in the drug sensitivity and CNI distribution into T cells. Because of this, measuring pharmacodynamic indicators linked to the suppression of calcineurin may better represent the biological action of CNIs in specific individuals. Systemic CNI trough concentrations are not always a good predictor of the biological activity of the medications in immune cells.
Aim: To conduct a comprehensive review on the use of pharmacodynamic indicators (calcineurin phosphatase activity and nuclear factor of activated T-cells activity) in renal transplant patients' monitoring of tacrolimus activity.
Methods: A systematic search was conducted in PubMed, Cochrane databases to collect and analyze all studies published from year 1995 till 2021; that investigated the role of Pharmacodynamic markers (Calcineurin phosphatase activity and Nuclear Factor of Activated T-cells activity) in monitoring tacrolimus activity in renal transplant patients. Randomised controlled trials and observational studies were included.
Results: Two studies met the inclusion criteria. The clinical value of pharmacodynamic monitoring on tacrolimus based renal transplant studies based on NFAT related gene expression should be evaluated in more prospective studies.
Conclusion: Our review indicates that the measurement of pharmacodynamic biomarkers plays an important role in monitoring tacrolimus activity in renal transplant patients.Author(s): Pingali Usha Rani, Mekala Padmaja, Gangadhar Taduri, Mohammed Abid Ali, Imran Khan