Tacrolimus intrapatient variability in solid organ transplantation: A multiorgan perspective

Area of Science:

• Pharmacology
• Transplantation Medicine
• Immunology

Background:

• Tacrolimus therapy in solid organ transplant (SOT) recipients presents challenges due to its narrow therapeutic window and significant pharmacokinetic variability.
• Intrapatient variability (IPV) in tacrolimus trough concentrations is emerging as a key predictor of transplant success.
• Understanding tacrolimus IPV is crucial for optimizing patient management and improving long-term outcomes.

Purpose of the Study:

• To review the association between tacrolimus IPV and graft/patient outcomes in SOT recipients.
• To identify potential interventions aimed at reducing tacrolimus IPV.
• To synthesize current evidence on the clinical significance of tacrolimus variability.

Main Methods:

• A systematic literature review was conducted using PubMed and Embase databases.
• Studies published from database inception to September 20, 2020, were included if they assessed tacrolimus IPV and transplant outcomes.
• Included studies encompassed both pediatric and adult SOT recipients, focusing on measures like standard deviation, coefficient of variation, and time in therapeutic range.

Main Results:

• Forty-four observational studies (2008-2020) met the inclusion criteria, with a majority focusing on adult kidney transplant recipients.
• High tacrolimus IPV was significantly associated with increased risk of acute rejection, de novo donor-specific antibody (dnDSA) formation, graft loss, and reduced patient survival.
• Evidence regarding interventions to improve tacrolimus IPV was limited to small, preliminary studies.

Conclusions:

• Elevated tacrolimus IPV is a significant risk factor for adverse outcomes in SOT recipients, including rejection, dnDSA, graft loss, and mortality.
• Further prospective research is warranted to develop and evaluate interventions targeting tacrolimus IPV.
• Stabilizing tacrolimus IPV may represent a promising strategy to enhance long-term transplant success.