Medication Level Variability During First Year After Pediatric Kidney Transplantation

Area of Science:

• Nephrology
• Immunology
• Pharmacology

Background:

• Tacrolimus (TAC) level variability, assessed by Medication Level Variability Index (MLVI) and intrapatient variability (IPV), may impact graft outcomes in solid organ transplant recipients.
• Optimal methods, timing, and thresholds for measuring TAC variability in pediatric kidney transplant recipients (peds KTRs) are not well-defined.

Purpose of the Study:

• To evaluate the association between TAC variability (MLVI and IPV) and graft outcomes in peds KTRs.
• To identify optimal time intervals for assessing TAC variability and its predictive value for graft failure and de novo donor-specific antibody (dnDSA) development.

Main Methods:

• Retrospective analysis of 149 peds KTRs on maintenance TAC immunosuppression.
• MLVI and IPV calculated across three intervals: 2-week to 3-month, 3- to 6-month, and 6- to 12-month post-transplant.
• Landmark survival analysis and survival trees used to assess associations and identify thresholds, adjusting for covariates.

Main Results:

• Both MLVI and IPV during the 2-week to 3-month and 6- to 12-month intervals were significantly associated with increased risk of graft failure.
• IPV during the 2-week to 3-month interval was significantly associated with de novo donor-specific antibody (dnDSA) development.
• Neither MLVI nor IPV predicted acute rejection; no significant associations were found for the 3- to 6-month interval.

Conclusions:

• Tacrolimus variability, both MLVI and IPV, during early (0-3 months) and later (6-12 months) post-transplant periods is linked to graft failure risk in pediatric kidney transplant recipients.
• Intrapatient variability (IPV) in the first 3 months is specifically associated with de novo donor-specific antibody development.