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15 June 2022 : Original article  

[In Press] Donor CYP3A5 Expression Decreases Renal Transplantation Outcomes in White Renal Transplant Recipients

Karola Warzyszyńska1ABCDEFG, Michał Zawistowski ORCID logo12BCDE, Edyta Karpeta3B, Agnieszka Jałbrzykowska4B, Maciej Kosieradzki1DE

DOI: 10.12659/AOT.936276

Ann Transplant In Press; DOI: 10.12659/AOT.936276  

Available online: 2022-06-15, In Press, Corrected Proof

Publication in the "In-Press" formula aims at speeding up the public availability of the pending manuscript while waiting for the final publication. The assigned DOI number is active and citable. The availability of the article in the Medline, PubMed and PMC databases as well as Web of Science will be obtained after the final publication according to the journal schedule

Abstract

BACKGROUND
After renal transplantation, immunosuppressants should be administered to prevent organ rejection and prolong graft survival. One of them is tacrolimus, which is metabolized by the CYP3A enzyme family. The variability of the CYP3A5 gene in renal transplant recipients has been previously studied for its correlation with acute rejection and allogeneic kidney function. CYP3A5 enzyme is also present in the renal tissue, and its relevance has not yet been extensively investigated. This study aimed to evaluate the effect of donor and recipient CYP3A5 expression status on early and long-term transplant outcomes.
MATERIAL AND METHODS
Single-nucleotide polymorphism in CYP3A5 (rs776746) was analyzed in 95 kidney transplant recipients and their grafts. The effect of donor and recipient genotypes on the primary endpoint, which was the loss of the renal graft over 5-year follow-up, was assessed. The secondary endpoints were biopsy-proven acute rejection, proteinuria, delayed graft function, and renal function.
RESULTS
Patients who received a CYP3A5*1 allele-carrying kidney (n=16) were at greater risk of graft loss (adjusted hazard ratio, 95% CI: 10.61, 2.28-49.42, P=.003) than those with the CYP3A5*3/*3 genotype (n=79). Renal CYP3A5 expression was also a predictor of acute rejection between the 2nd and 12th post-transplant months (adjusted odds ratio, 95% CI: 4.36; 1.08-17.6, P=.038) and proteinuria at different time intervals. No effect of the recipient CYP3A5 genotype was observed.
CONCLUSIONS
The donor CYP3A5 genotype is associated with inferior transplantation outcomes. Local renal tacrolimus metabolism is a potential target for improving long-term transplantation outcomes.

Keywords: Delayed Graft Function; Graft Rejection; Graft Survival; Kidney Transplantation; Proteinuria; CYP3A5 Protein, Human

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Donor CYP3A5 Expression Decreases Renal Transplantation Outcomes in White Renal Transplant Recipients

Ann Transplant In Press; DOI: 10.12659/AOT.936276  

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Annals of Transplantation eISSN: 2329-0358
Annals of Transplantation eISSN: 2329-0358