Tacrolimus trough and dose intra‐patient variability and CYP3A5 genotype: Effects on acute rejection and graft failure in European American and African American kidney transplant recipients

Background Suboptimal immunosuppression after kidney transplantation contributes to toxicity and loss of efficacy. Little is known regarding the impact of intra‐patient variability of tacrolimus (TAC) doses and troughs in the early post‐transplant period or the influence of genetic variants on varia...

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Bibliographic Details
Published in:Clinical transplantation 2018-12, Vol.32 (12), p.e13424-n/a
Main Authors: Seibert, Stephan R., Schladt, David P., Wu, Baolin, Guan, Weihua, Dorr, Casey, Remmel, Rory P., Matas, Arthur J., Mannon, Roslyn B., Israni, Ajay K., Oetting, William S., Jacobson, Pamala A.
Format: Article
Language:English
Subjects:
acute rejection
Adolescent
Adult
Aged
Aged, 80 and over
Black or African American - genetics
Cytochrome P-450 CYP3A - genetics
Dose-Response Relationship, Drug
Female
Follow-Up Studies
Genotype
graft failure
Graft Rejection - drug therapy
Graft Rejection - epidemiology
Graft Rejection - etiology
Graft Survival - drug effects
Graft Survival - genetics
Humans
Immunosuppressive Agents - therapeutic use
Incidence
intra‐patient variability
Kidney Failure, Chronic - surgery
kidney transplant
Kidney Transplantation - adverse effects
Male
Middle Aged
Minnesota - epidemiology
Postoperative Complications
Prognosis
Prospective Studies
Risk Factors
tacrolimus
Tacrolimus - therapeutic use
White People - genetics
Young Adult
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Summary:Background Suboptimal immunosuppression after kidney transplantation contributes to toxicity and loss of efficacy. Little is known regarding the impact of intra‐patient variability of tacrolimus (TAC) doses and troughs in the early post‐transplant period or the influence of genetic variants on variability. Methods Coefficients of variation (CV) of TAC troughs and doses of 1226 European American (EA) and 246 African American (AA) adult recipients enrolled in DeKAF Genomics were compared for association with acute rejection and graft failure. Additionally, the influence of recipients’ number of CYP3A5 loss‐of‐function alleles was assessed. Results Acute rejection was associated with greater CV of dose in AA (P 
ISSN:0902-0063
1399-0012
DOI:10.1111/ctr.13424