The effect of CYP3A4 genetic polymorphisms on the pharmacokinetics of calcineurin inhibitors in renal transplant recipients: a systematic review and meta-analysis protocol

Background: Calcineurin inhibitors (CNIs) are metabolized by CYP3A4. Polymorphisms in the CYP3A4 gene alter the activity of CYP3A4 protein and therefore affect the CNIs concentrations. Results of studies that investigated the association between CYP3A4 polymorphisms and CNIs pharmacokinetics are controversial. Therefore, this systematic review and meta-analysis will evaluate the effect of CYP3A4 polymorphisms on the pharmacokinetics of CNIs in renal transplant recipients. Method: This protocol is developed according to the PRISMA-P guideline and registered in PROSPERO (CRD42020145219). The MeSH/Emtree terms of CYP3A4 polymorphisms and CNIs pharmacokinetics in PECO-based question will be obtained from the comprehensive literature search on PubMed/MEDLINE, Scopus, Web of Science, Embase, CENTRAL, and ProQuest without any language limitation from 1 January 1998 to 31 March 2021. Google Scholar search engine, registries, conference papers, and key journals will also be searched. Screening, selection, quality assessment, and data extraction will be performed by two independent reviewers. Statistical heterogeneity will be calculated by the Q Cochrane test and I2 statistic. Publication bias and sensitivity analysis will be evaluated by appropriate tests. Results and conclusion: According to the meta-analysis of the aggregated data from the relevant primary studies, the association between CYP3A4 polymorphisms and CNIs pharmacokinetics will be reported, which possibly help the pharmacogenetic-guided dosing approach.

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Non-adherence to immunosuppressants following renal transplantation: a protocol for a systematic review

BMJ Open ◽

10.1136/bmjopen-2016-015411 ◽

2017 ◽

Vol 7 (9) ◽

pp. e015411 ◽

Cited By ~ 6

Author(s):

Abigail Hucker ◽

Frances Bunn ◽

Lewis Carpenter ◽

Christopher Lawrence ◽

Ken Farrington ◽

...

Keyword(s):

Systematic Review ◽

Renal Transplant ◽

Data Extraction ◽

Meta Analysis ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Data Extraction Form ◽

Registration Number ◽

Meta Analyses ◽

The Impact

IntroductionAdherence to immunosuppressant medication is essential for renal transplant recipients. This review aims to summarise what is known about non-adherence, with a view to providing comprehensive evidence to inform strategies aimed at advancing adherent behaviour.Methods and analysisA systematic review of quantitative studies that report adherence to immunosuppressants in adult (over 18 years) renal transplant recipients. The review will follow the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines; study quality will be assessed using the Downs and Black checklist. Systematic searches will be completed across relevant databases. Two reviewers will independently extract data using a predefined data extraction form. We will summarise the operationalisation of adherence across studies and use narrative synthesis to identify factors associated with non-adherence. A meta-analysis will be conducted if there is sufficient homogeneity, and available data, across studies to estimate the prevalence of non-adherence in renal transplant recipients. Heterogeneity will be assessed using the I2test. Survival analysis will be conducted to estimate hazard ratios to explore the impact of non-adherence on graft survival, graft failure and patient survival.Ethics and disseminationFindings will be published in a peer-reviewed journal and disseminated at conferences for professionals and researchers. Review outcomes will help support clinical practice by highlighting the extent of non-adherence among adults, and in doing so, signpost the need for suitable intervention.Trial registration numberPROSPERO registration number (CRD42016038751).

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