Analysis of the Effect of Donor CYP3A5 Gene Polymorphism on Early Tacrolimus Concentration and Postoperative Acute Renal Injury After Liver Transplantation

March 12, 2024 updated by: Ziqiang Li
Tacrolimus is the most commonly used immunosuppressant for preventing and treating rejection after liver transplantation. However, its treatment window is narrow, the pharmacokinetic individual differences are large, routine dose according to body weight, sometimes low dose will cause graft rejection of patients, or high dose will lead to infection and liver and kidney toxicity and other adverse reactions. Moreover, the conventional drug testing can not fully reflect the efficacy of tacrolimus, and there are shortcomings of lag, experience and passivity. FK506 is metabolized primarily by cytochrome P450 member 3A5 in the liver and intestines. CYP3A5*3 is the most important factor determining the expression level of CYP3A5. This mutation can cause variable shear and produce unstable protein, so that patients carrying CYP3A5*3/*3 gene do not express CYP3A5. Acute kidney injury is a common and important complication after liver transplantation. Despite recent advances in organ preservation, surgical techniques, and immunosuppressive protocols, the incidence of AKI after orthotopic liver transplantation remains high. AKI has a significant impact on both short - and long-term prognosis of orthotopic liver transplantation recipients. Studies have shown that orthotopic liver transplantation recipients with AKI have significantly higher mortality rates in hospital, at 28 days and at 1 year after surgery than those without AKI. In this study, the relationship between donor and recipient CYP3A5 gene polymorphism and tacrolimus concentration was investigated, and the effect of donor and recipient CYP3A5 gene polymorphism and tacrolimus concentration on acute kidney injury after liver transplantation was investigated. To provide guidance for individual administration of gene-directed tacrolimus in patients, and provide basis for prevention and reduction of postoperative acute kidney injury in liver transplantation patients.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

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Intervention / Treatment

Intervention / Treatment

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Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
60

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Shandong
      • Jinan, Shandong, China, 250013
        • The First Affiliated Hospital of Shandong First Medical University (Qianfoshan Hospital)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

60 patients receiving liver transplantation at the center of Qianfoshan Hospital in 2022.01-2023.06

Description

Inclusion Criteria:

  1. Patients undergoing orthotopic liver transplantation in our center.
  2. The postoperative immunosuppression regimen was tacrolimus、methylprednisolone and balipremumab for injection in all cases,and no drugs that interacted with tacrolimus were used.
  3. The postoperative follow-up time was greater than 6 months and no serious rejection occurred during the follow-up period.

Exclusion Criteria:

  1. Combined organ transplantation.
  2. liver transplant patients on other immunosuppressive regimens.
  3. Preoperative CKD or need RRT.
  4. Preoperative serum creatinine (SCr) > 133 mol/L.
  5. Loss of follow-ups.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
donor/acceptor expression group
Other: CYP3A5*1*、CYP3A5*1*3
2ml of venous blood was drawn and placed in an EDTA anticoagulant tube. Peripheral blood genomic DNA was extracted according to the instructions of the DNA extraction kit.The reaction system was prepared by polymerase chain reaction (PCR) according to the instructions of PCR amplification system. After 25g/L agarose gel electrophoresis, the bands of amplified products were observed under UV lamp. The PCR products were purified by enzymolysis. The purified product was prepared according to sequencing PCR amplification system. After 1min predenaturation at 96℃, denaturation at 96℃ for 30s, annealing at 56 ℃ for 30s and extension at 72℃ for 1 cycle. A total of 25 cycles were performed for sequencing PCR amplification. The amplified products were purified by ethanol precipitation method.
donor expression/acceptor non-expression
donor non-expression/acceptor expression
donor/acceptor non-expression group
Other: CYP3A5*3*3
2ml of venous blood was drawn and placed in an EDTA anticoagulant tube. Peripheral blood genomic DNA was extracted according to the instructions of the DNA extraction kit.The reaction system was prepared by polymerase chain reaction (PCR) according to the instructions of PCR amplification system.After 25g/L agarose gel electrophoresis, the bands of amplified products were observed under UV lamp. The PCR products were purified by enzymolysis. The purified product was prepared according to sequencing PCR amplification system. After 1min predenaturation at 96℃, denaturation at 96℃ for 30s, annealing at 56 ℃ for 30s and extension at 72℃ for 1 cycle. A total of 25 cycles were performed for sequencing PCR amplification. The amplified products were purified by ethanol precipitation method.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Fk506
Time Frame: 1-28 days postoperatively
Tacrolimus concentration
1-28 days postoperatively
Scr
Time Frame: 1-28 days postoperatively
Reflects indicators of kidney function
1-28 days postoperatively

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Ziqiang Li

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Liziqiang Liziqiang, Doctor, Party

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 1, 2024

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 5, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 12, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 20, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 20, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 12, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • JSZ007

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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