TruGraf and TRAC In Pediatrics Study

Study Overview
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Brief Summary
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This is a pilot 3 center prospective study of pediatric renal kidney recipients undergoing protocol biopsies examining the performance of the TruGraf gene expression test in children and adolescents.

Detailed Description
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In pediatric renal transplant recipients, subclinical rejection in protocol biopsies is associated with a significantly increased incidence of acute rejection and/or allograft loss at 5 years post-transplant. Currently, TruGraf is the only noninvasive test designed and validated in adult kidney transplant recipients for use in ruling out silent subacute rejection in that has been approved by Medicare as an alternative to surveillance biopsies. The first step to the use of TruGraf in pediatrics is to perform a validation study in children and adolescents. Specifically, if validated in children and adolescents, a TruGraf result would enable a pediatric transplant physician to identify patients in whom no intervention is necessary without the need of a protocol biopsy. Therefore the aim of this study is to examine the concordance between the results of the TruGraf tests and protocol biopsies taken from stable pediatric renal transplant patients concurrently.

Official Title
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The Role of TruGraf® to Optimize Outcomes in Pediatric Renal Transplantation

Conditions
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Kidney Transplant Rejection

Intervention / Treatment
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* Diagnostic Test: Patients monitored with TruGraf and TRAC testing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged 1-≤ 18 years and recipients of either living or deceased donor transplants Undergoing a protocol biopsy at either 3, 6, 12, 24 or 36 months Serum creatinine at the time of the clinic visit prior to the scheduled biopsy within 30% of a baseline calculated as the mean of the recipient's last 3 serum creatinine levels Serum creatinine level at the time of protocol biopsy ≤ 1.7 mg/dl. Patient receiving immunosuppression with a calcineurin inhibitor (either tacrolimus or cyclosporine) and/or an antimetabolite (either mycophenolate mofetil, mycophenolic acid EC or azathioprine) and/or an mTOR inhibitor (either sirolimus or everolimus) and/or corticosteroids. Absence of any systemic or urinary bacterial, viral or fungal infection Absence of significant BK viremia (as determined by the laboratory where the determination is run) at the time of the last clinical determination and at the time of the protocol biopsy Parents or guardians are capable of reading and understanding the Informed Consent document and willing to participate; if appropriate, patient is also able to understand the Informed Consent. If patient is older than 13 years, patient should be able to give Assent as written on Assent Form. For females of child-bearing age, a negative pregnancy test within 6 weeks of the protocol biopsy. Exclusion Criteria: Refusal to undergo clinical standard-of-care protocol biopsy by either parent/guardian or patient. Inability to obtain adequate tissue on protocol biopsy Current participation in another interventional research study; patients who have completed the drug in another interventional study are eligible if they meet all other inclusion criteria. Serum creatinine at the clinic visit prior to the biopsy is > 30% of a baseline calculated as the mean of the recipient's last 3 serum creatinine levels. Serum creatinine at the time of the protocol biopsy ≥ 1.8 mg/dl. If the patient had a baseline < 1.8, and the creatinine on the day of biopsy is ≥ 1.8, at the discretion of the PI, the patient will be instructed to hydrate for 4 days and a serum creatinine will be obtained at that time. This is standard clinical practice. If the creatinine returns to the baseline (i.e., ≤ 30%) range, the patient will be classified as having stable renal function, while if the patient's serum creatinine does not return to the ≤ 30% range, he/she will be classified as having renal dysfunction Patients who, in the estimation of the investigator, are undergoing for-cause biopsies. Presence of any current and active bacterial, viral or fungal infection Presence of BK viremia judged to be significant by the site PI. Presence of BK nephropathy History of PTLD or malignancy Parents / guardians do not understand Informed Consent and / or are unwilling to participate; patient, if of appropriate age, is unwilling to participate Patients manifesting recurrent disease in their transplant (such as FSGS/nephrotic syndrome, C3 Glomeruopathy, MPGN, hyperoxaluria) Abnormal proteinuria as determined by a urinary protein: creatinine ratio of >1. Recipients of multi-organ transplants.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Diagnostic Test: Patients monitored with TruGraf and TRAC testing|This is an observational study there are no protocol mandated interventions. TruGraf and TRAC results will be utilized in conjunction with standard of care assessments to determine patient management.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concordance of Biomarkers with protocol biopsy | Examination of the concordance between the results of the TruGraf tests and protocol biopsies taken from stable pediatric renal transplant concurrently. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concordance between the results of the TruGraf test and the histological finding of borderline changes vs. TCMR vs. AMR. | Separately examine the concordance between the results of the TruGraf test and the histological finding of borderline changes vs. TCMR vs. AMR. | 1 year | 
| Compare TruGraf results in patients ≤ 11 years old vs ≥ 12 years old | Compare the agreement between protocol biopsies and TruGraf results in patients ≤ 11 years old vs ≥ 12 years old | 1 year | 
| Relationship between de novo DSA, a normal protocol biopsy and the TruGraf result. | Assess the relationship, if any, between the appearance of de novo DSA, a normal protocol transplant biopsy and the TruGraf result. | 1 year | 
| Examine TruGraf results and the %CV tacrolimus levels- index of medication nonadherence. | Examine the relationship between the TruGraf results and the %CV tacrolimus levels as an index of medication nonadherence. | 1 year | 
| Relationship between urinary CXCL10 and subclinical rejection affecting the predictive value of TruGraf. | Examine the relationship between urinary CXCL10 and subclinical rejection in this patient cohort to examine whether it improves the performance metrics by improving the negative or positive predictive of TruGraf. | 1 year | 
| Examine relationship between ddcfDNA and subclinical rejection | Examine the relationship between ddcfDNA and subclinical rejection in this patient cohort | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Biomarkers, Subclinical Rejection, Biopsy