Tacrolimus variability is associated with de novo donor-specific antibody development in pediatric renal transplant recipients

Background Donor-specific antibody (DSA) is a risk factor for antibody-mediated rejection and shortened graft survival. We investigated the role of intrapatient variability in tacrolimus trough levels on graft outcomes (i.e., de novo DSA, rejection, graft loss) in pediatric renal transplant recipien...

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Bibliographic Details
Published in:Pediatric nephrology (Berlin, West) West), 2020-02, Vol.35 (2), p.261-270
Main Authors: Solomon, Sonia, Colovai, Adriana, Del Rio, Marcela, Hayde, Nicole
Format: Article
Language:English
Subjects:
Adolescent
Age
Age Factors
Child
Child, Preschool
Cohort Studies
Female
Graft rejection
Graft Rejection - immunology
Graft Rejection - prevention & control
Health risk assessment
Humans
Immunosuppression
Immunosuppressive Agents - blood
Immunosuppressive Agents - therapeutic use
Infant
Isoantibodies
Kidney Transplantation
Male
Medicine
Medicine & Public Health
Nephrology
Original Article
Pediatrics
Population studies
Retrospective Studies
Risk factors
Tacrolimus
Tacrolimus - blood
Tacrolimus - therapeutic use
Transplant Recipients
Urology
Variability
What’s New in Renal Transplantation
Young Adult
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Summary:Background Donor-specific antibody (DSA) is a risk factor for antibody-mediated rejection and shortened graft survival. We investigated the role of intrapatient variability in tacrolimus trough levels on graft outcomes (i.e., de novo DSA, rejection, graft loss) in pediatric renal transplant recipients. Methods This was a single-center retrospective study which included 38 pediatric renal transplant recipients. Intrapatient tacrolimus variability was defined using the coefficient of variation (CV; SD/Mean × 100) for all levels obtained after 3 months post-transplant. CV cut-points of 30%, 40%, and 50% were used in the analyses. Results The median CV 43.1% (35.0%, 58.6%). Out of 38 patients, 19 (50%) developed de novo DSA. In the logistic regression model, after adjusting for age, rejection history, maintenance immunosuppression, and CV, for every 10% increase in tacrolimus variability, the odds of developing de novo DSA increased by 53% ( p  = 0.048, CI 1.0005, 1.11). Age at transplant was also an independent risk factor for DSA development; every 1 year increase in age was associated with a 31% increase in the odds of developing DSA ( p  = 0.03, CI 1.03, 1.67). At a CV cut-point ≥ 30%, higher tacrolimus variability was associated with an increased incidence of allograft rejection (0% vs 42%,
ISSN:0931-041X
1432-198X
DOI:10.1007/s00467-019-04377-6