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Abstract: FR-PO1185

Prevalence of CYP3A Haplotype and Its Relation to Calcineurin Inhibitors Toxicity in Patients with Renal Transplantation Greater Than a Year in Western Mexico

Session Information

Category: Transplantation

  • 1902 Transplantation: Clinical

Authors

  • Sanchez Vazquez, Omar Humberto, Instituto Mexicano del Seguro Social, Guadalajara, Mexico
  • Garcia Rivera, Alejandro, Instituto Mexicano del Seguro Social, Guadalajara, Mexico
  • Parra Michel, Renato, Universidad de Guadalajara, Centro Universitario de Ciencias de la Salud, Hospital General Regional No.46, Instituto Mexicano del Seguro Social., Zapopan, jalisco, Mexico
  • Leal, Caridad, Instituto Mexicano del Seguro Social, Guadalajara, Mexico
  • Garcia-Vera, Ana Lya, Instituto Mexicano del Seguro Social, Guadalajara, Mexico
  • Cisneros-Carbajal, Marlene Del rocio, Instituto Mexicano del Seguro Social, Guadalajara, Mexico
  • Murga, Antonio Mariano, Instituto Mexicano del Seguro Social, Guadalajara, Mexico
  • Fonseca cerda, Carlos Francisco, Instituto Mexicano del Seguro Social, Guadalajara, Mexico
  • Topete reyes, Jorge fernando, Universidad de Guadalajara, Centro Universitario de Ciencias de la Salud, Hospital General Regional No.46, Instituto Mexicano del Seguro Social., Zapopan, jalisco, Mexico
  • Flores, Silvia, Instituto Mexicano del Seguro Social, Guadalajara, Mexico
  • Mendoza, Francisco, Instituto Mexicano del Seguro Social, Guadalajara, Mexico
  • Jimenez Mejia, Carlos Daniel, Instituto Mexicano del Seguro Social, Guadalajara, Mexico
Background

ESRD is a public worldwide health problem and kidney transplantation is the RRT of choice. Immunosuppressive treatment with tacrolimus has significantly improved short-term graft survival. It has a narrow therapeutic index and a pharmacokinetic variability that may predispose to nephrotoxicity. Polymorphisms of cP450 (CYP3A4 and CYP3A5) have been related to variability in tacrolimus metabolism.

Methods

Retrospective study in 338 patients with renal transplant over a year being cared in our hospital, in treatment with tacrolimus, January 2017 - January 2018. Genotyping of the variants CYP3A5*3, CYP3A5*1, CYP3A4*1, and CYP3A4*1b was performed and frequency of nephrotoxicity and blood tacrolimus levels were associated with each of the genotypes.

Results

The most frequent polymorphisms were CYP3A5*3/*3 in 53% and CYP3A4*1/*1 in 84%. The most frequent haplotype was CYP3A5*3/*3 + CYP3A4*1/*1 in 50.59%, followed by CYP3A5*1/*3 + CYP3A4*1/*1. Figure 1 shows the behavior of the CYP3A polymorphisms. CYP3A4*1b/*1b and CYP3A5*1/*1 required the highest tacrolimus weight dose and had the lowest blood tacrolimus levels, statistically different from CYP3A*1/*1 and CYP3A5*3/*3, respectively. The comparison between different haplotypes showed a significant difference only in the weight dose, not in the tacrolimus blood levels. There was no significant statistical difference in CNI toxicity.

Conclusion

In the western Mexican population, CYP3A4*1/*1 and CYP3A5*3/*3 are the most prevalent polymorphisms, with a slow metabolizer profile. Recipients with CYP3A4*1b/*1b or CYP3A5*1/*1 polymorphisms require higher tacrolimus dosage and show a tendency to have higher rates of CNI toxicity despite having low tacrolimus blood levels.