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Use of Pharmacogenetics to Optimize Immunosuppressant Therapy in Kidney-Transplanted Patients.

ABSTRACT: Immunosuppressant drugs (ISDs) are routinely used in clinical practice to maintain organ transplant survival. However, these drugs are characterized by a restricted therapeutic index, a high inter- and intra-individual pharmacokinetic variability, and a series of severe adverse effects. In particular, genetic factors have been estimated to play a role in this variability because of polymorphisms regarding genes encoding for enzymes and transporters involved in the ISDs pharmacokinetic. Several studies showed important correlations between genetic polymorphisms and ISDs blood levels in transplanted patients; therefore, this review aims to summarize the pharmacogenetics of approved ISDs. We used PubMed database to search papers on pharmacogenetics of ISDs in adults or pediatric patients of any gender and ethnicity receiving immunosuppressive therapy after kidney transplantation. We utilized as search term: "cyclosporine or tacrolimus or mycophenolic acid or sirolimus or everolimus and polymorphism and transplant". Our data showed that polymorphisms in CYP3A5, CYP3A4, ABCB1, and UGT1A9 genes could modify the pharmacokinetics of immunosuppressants, suggesting that patient genotyping could be a helpful strategy to select the ideal ISDs dose for each patient.

SUBMITTER: Urzi Brancati V

PROVIDER: S-EPMC9332547 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Use of Pharmacogenetics to Optimize Immunosuppressant Therapy in Kidney-Transplanted Patients.

Urzì Brancati Valentina V Scarpignato Carmelo C Minutoli Letteria L Pallio Giovanni G

Biomedicines 20220726 8

Immunosuppressant drugs (ISDs) are routinely used in clinical practice to maintain organ transplant survival. However, these drugs are characterized by a restricted therapeutic index, a high inter- and intra-individual pharmacokinetic variability, and a series of severe adverse effects. In particular, genetic factors have been estimated to play a role in this variability because of polymorphisms regarding genes encoding for enzymes and transporters involved in the ISDs pharmacokinetic. Several s ...[more]

PMID: 35892699

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Project description:Chronic kidney disease is associated with an increased risk of fracture and cardiovascular mortality. The risk of fracture in hemodialysis (HD), peritoneal dialysis (PD) and kidney transplant (KT) patients is higher when compared with the general population. However, there exists a knowledge gap concerning which group has the highest risk of fracture. We aimed to compare the risk of fracture in HD, PD, and KT populations. We conducted a systematic review of observational studies evaluating the risk of fracture in HD, PD, or KT patients. Eligible studies were searched using MEDLINE, Embase, Web of Science, and Cochrane Library from their inception to January 2016, and in grey literature. Incidences (cumulative and rate) of fracture were described together using the median, according to fracture sites, the data source (administrative database or cohort and clinical registry), and fracture diagnosis method. Prevalence estimates were described separately. We included 47 studies evaluating the risk of fracture in HD, PD, and KT populations. In administrative database studies, incidence of hip fracture in HD (median 11.45 per 1000 person-years [p-y]), range: 9.3 to 13.6 was higher than in KT (median 2.6 per 1000 p-y; range 1.5 to 3.8) or in PD (median 5.2 per 1000 p-y; range 4.1 to 6.3). In dialysis (HD+PD), three studies reported a higher incidence of hip fracture than in KT. Prevalent vertebral fracture (assessed by X-rays or questionnaire) reported in HD was in a similar range as that reported in KT. Incidence of overall fracture was similar in HD and KT, from administrative databases studies, but lower in HD compared with KT, from cohorts or clinical registry studies. This systematic review suggests an important difference in fracture risk between HD, PD, and KT population, which vary according to the diagnosis method for fracture identification. © 2018 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Dataset Information

Use of Pharmacogenetics to Optimize Immunosuppressant Therapy in Kidney-Transplanted Patients.

Publications

Use of Pharmacogenetics to Optimize Immunosuppressant Therapy in Kidney-Transplanted Patients.

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