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| Name | Class |
|---|---|
| Third Affiliated Hospital, Sun Yat-Sen University | OTHER |
| 181 Central Hospital of the Chinese PLA | OTHER |
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The purpose of this study is to determine whether functional genetic variants can affect tacrolimus dose corrected trough levels and associate with the side effects in Chinese renal transplant recipients.
Tacrolimus is an effective immunosuppressive drug widely used in solid organ transplantation to prevent rejection. It is characterized by a narrow therapeutic range and large inter- and intra- individual variability in its pharmacokinetics. Many factors are associated with the variability. Of these factors, genetic factor play an important role. Full understanding of this mechanism is important for the personalized use of tacrolimus and reducing the risk of side effects.The CYP3A5*3 (A6986G) resulting in a splicing defect and the absence of protein activity, was identified as a functional variant (Kuehl P.2001). The CYP3A4*1G was also reported as a functional variant (Richards-Waugh LL. 2014). In addition, other functional variants will also be identified and analyzed in our project.
Our project has two parts:first, retrospective study, 839 renal transplant recipients using tacrolimus as immunosuppressive drug were recruited from Nanfang Hospital. Fifty-eight SNPs from GWAS, GTEx and promoter region of CYP3A gene were genotyped. The association of 58 SNPs on the dose corrected tacrolimus trough levels and side effects (acute rejection, nephrotoxicity and neurotoxicity) were analyzed. Luciferase reporter gene assay were used to identify the functional variants. Second, in this part, there is another renal transplantation cohort. For this cohort, it was a retrospective cohort. All the patients will be stratified to different groups according to the different genotypes. The side effects (acute rejection, nephrotoxicity and neurotoxicity) will be observed.During the study period, all the therapeutic procedures of the patients are as usual.
This will be the largest cohort of this kind of study in Chinese population. The findings will be useful for the patients to improve the therapeutic efficacy and reduce the side effects.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 | The retrospective cohort consists of about 839 kidney transplant recipients from Nanfang Hospital. These patients used tacrolimus as immunosuppressive drug for preventing the rejection.The side effects (acute rejection, nephrotoxicity and neurotoxicity) will be recorded. | ||
| Cohort 2 | The retrospective cohort consists of about 663 kidney transplant recipients from Guilin No. 924 Hospital. These patients used tacrolimus as immunosuppressive drug for preventing the rejection.The side effects (acute rejection, nephrotoxicity and neurotoxicity) will be recorded. |
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| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Acute Rejection | We will measure the number of participants with acute rejection during the day 1 to day 61 after transplantation. Kaplan-Meier analyses were performed for acute rejection in participants with different genotypes. | Day 1 to Day 61 |
| Number of Participants With Tacrolimus-related Nephrotoxicities | We will measure the number of participants with tacrolimus-related nephrotoxicities during the day 1 to day 61 after transplantation. Kaplan-Meier analyses were performed for tacrolimus-related nephrotoxicities in participants with different genotypes. | Day1 to Day 61 |
| Number of Participants With Tacrolimus-related Neurotoxicities | We will measure the number of participants with tacrolimus-related neurotoxicities during the day 1 to day 61 after transplantation. Kaplan-Meier analyses were performed for tacrolimus-related neurotoxicities in participants with different genotypes. | Day1 to Day 61 |
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Inclusion Criteria:
Subject has been conducted kidney transplantation. Subject has used tacrolimus as immunosuppressant.
Exclusion Criteria:
Simultaneous liver-kidney transplantation. Patients with age less than 18 years old. Tacrolimus blood concentration monitoring less than 3 times. Failed to extract DNA.
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The study population consists of the renal transplant recipients who received tacrolimus as immunosuppressant from Nanfang Hospital and Guilin No.924 Hospital. All the patients are Chinese.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Nanfang Hospital | Guangzhou | Guangdong | 510515 | China | ||
| Guilin No.924 Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36927114 | Derived | Maseko N, Yang S, Li C, Zhang S, Wang R, Zhang Y, Li C, Zhang C, Li L. Impact of genetic polymorphisms on tacrolimus trough blood concentration in Chinese liver transplant recipients. Pharmacogenomics. 2023 Mar;24(4):207-217. doi: 10.2217/pgs-2022-0180. Epub 2023 Mar 17. | |
| 35977080 | Derived | Yang S, Jiang H, Li C, Lu H, Li C, Ye D, Qi H, Xu W, Bao X, Maseko N, Zhang S, Shao R, Li L. Genomewide association study identifies a novel variant associated with tacrolimus trough concentration in Chinese renal transplant recipients. Clin Transl Sci. 2022 Nov;15(11):2640-2651. doi: 10.1111/cts.13388. Epub 2022 Aug 28. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1 | The retrospective cohort consists of about 839 kidney transplant recipients from Nanfang Hospital. These patients used tacrolimus as immunosuppressive drug for preventing the rejection.The side effects (acute rejection, nephrotoxicity and neurotoxicity) will be recorded. |
| FG001 | Cohort 2 | The retrospective cohort consists of about 663 kidney transplant recipients from Guilin No. 924 Hospital. These patients used tacrolimus as immunosuppressive drug for preventing the rejection.The side effects (acute rejection, nephrotoxicity and neurotoxicity) will be recorded. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1 | The retrospective cohort consists of about 839 kidney transplant recipients from Nanfang Hospital. These patients used tacrolimus as immunosuppressive drug for preventing the rejection.The side effects (acute rejection, nephrotoxicity and neurotoxicity) will be recorded. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Acute Rejection | We will measure the number of participants with acute rejection during the day 1 to day 61 after transplantation. Kaplan-Meier analyses were performed for acute rejection in participants with different genotypes. | Posted | Number | participants | Day 1 to Day 61 |
|
Transplant recipients were followed for 61 days after transplantation to monitor side effects (acute rejection, nephrotoxicity and neurotoxicity).
All the participants are at risk for All-Cause Mortality.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort 1 | The retrospective cohort consists of about 839 kidney transplant recipients from Nanfang Hospital. These patients used tacrolimus as immunosuppressive drug for preventing the rejection.The side effects (acute rejection, nephrotoxicity and neurotoxicity) will be recorded. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute rejection | Renal and urinary disorders | Systematic Assessment | Acute rejection for kidney transplant recipients. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Liang Li | Southern Medical University | 86 20 61648510 | liliang@smu.edu.cn |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Sep 23, 2019 | Sep 24, 2019 | Prot_SAP_000.pdf |
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Human genomic DNA was extracted from leukocytes in patients' peripheral blood.
| Guilin |
| Guangxi |
| 541002 |
| China |
| Cohort 2 |
The retrospective cohort consists of about 663 kidney transplant recipients from Guilin No. 924 Hospital. These patients used tacrolimus as immunosuppressive drug for preventing the rejection.The side effects (acute rejection, nephrotoxicity and neurotoxicity) will be recorded. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
| Primary | Number of Participants With Tacrolimus-related Nephrotoxicities | We will measure the number of participants with tacrolimus-related nephrotoxicities during the day 1 to day 61 after transplantation. Kaplan-Meier analyses were performed for tacrolimus-related nephrotoxicities in participants with different genotypes. | Posted | Number | participants | Day1 to Day 61 |
|
|
|
| Primary | Number of Participants With Tacrolimus-related Neurotoxicities | We will measure the number of participants with tacrolimus-related neurotoxicities during the day 1 to day 61 after transplantation. Kaplan-Meier analyses were performed for tacrolimus-related neurotoxicities in participants with different genotypes. | Posted | Number | participants | Day1 to Day 61 |
|
|
|
| 0 |
| 819 |
| 256 |
| 819 |
| 0 |
| 819 |
| EG001 | Cohort 2 | The retrospective cohort consists of about 663 kidney transplant recipients from Guilin No. 924 Hospital. These patients used tacrolimus as immunosuppressive drug for preventing the rejection.The side effects (acute rejection, nephrotoxicity and neurotoxicity) will be recorded. | 0 | 631 | 37 | 631 | 0 | 631 |
|
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