Trifecta-Kidney cfDNA-MMDx Study
- Conditions
- Kidney Transplant Rejection
- Interventions
- Diagnostic Test: MMDxDiagnostic Test: ProsperaDiagnostic Test: HLA antibody
- Registration Number
- NCT04239703
- Lead Sponsor
- University of Alberta
- Brief Summary
Demonstrate the relationship between DD-cfDNA levels and HLA antibodies in blood, and the Molecular Microscope® (MMDx) Diagnostic System results in indication biopsies.
- Detailed Description
There is a need for better screening of kidney transplant patients for rejection. Patients with kidney transplants are routinely tested (creatinine, urine protein, histology and donor specific antibody (DSA) as standard of care to detect rejection, but these tests are not adequate. Rejection is often missed by these tests (false negatives) and other processes such as acute kidney injury can produce false-positive results. Moreover, histology has a high interobserver disagreement diagnosing rejection, and cannot accurately assess acute injury. A definitive molecular assessment of rejection and injury in kidney biopsies has emerged - the Molecular Microscope® Diagnostic System (MMDx) - developed by the Alberta Transplant Applied Genomics Centre, University of Alberta. Now a new screening test is being introduced: the monitoring of donor-derived cell-free DNA (DD-cfDNA) released in the blood by the kidney during rejection. The Natera Inc DD-cfDNA Prospera® test is based on the massively multiplex PCR that targets 13,392 single nucleotide polymorphisms and targeted sequences are quantified by Next Generation Sequencing. The Prospera® test done on kidney transplant recipients detected "active rejection" and differentiated it from borderline rejection and no rejection. It is likely, however, that DD-cfDNA test may miss some T cell-mediated rejection (TCMR) cases and the distinction between early and fully developed antibody-mediated rejection (ABMR) was not tested. No study has actually examined the DD-cfDNA results in kidney transplants with acute or chronic kidney disease (AKI and CKD). DD-cfDNA measurements have only been correlated with histology, a flawed standard. DD-cf-DNA test must now be calibrated against MMDx that is based on global gene expression, the new standard for biopsy interpretation. The present study will calibrate centrally measured (Natera Inc) DD-cfDNA levels obtained at the time of an indication biopsy against the MMDx measurements of TCMR, and ABMR (early-stage, fully-developed, and late-stage), AK, and atrophy-fibrosis. We will compare blood DD-cfDNA measurements in 600 samples at the time of 300 indication biopsies to the MMDx results, as well as central assessment of HLA antibody (One Lambda) in 300 blood samples, interpreted centrally as DSA based on the tissue typing results. This study is an extension of the INTERCOMEX ClinicalTrials.gov Identifier: NCT01299168. We have collected 1203 kidney biopsies and 2422 corresponding blood samples. We extend this study to the total of 1400 biopsies and 2800 blood samples.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 300
- All kidney transplant recipients undergoing a kidney biopsy for clinical indications, as determined by their physician or surgeon, will be eligible to enroll in the study.
- Patients will be excluded from the study if they decline participation or are unable to give informed consent or multiple organ recipients.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Kidney transplant biopsies for cause HLA antibody The study population includes patients with a functioning kidney transplant undergoing a biopsy for clinical indications as standard of care. Kidney transplant biopsies for cause MMDx The study population includes patients with a functioning kidney transplant undergoing a biopsy for clinical indications as standard of care. Kidney transplant biopsies for cause Prospera The study population includes patients with a functioning kidney transplant undergoing a biopsy for clinical indications as standard of care.
- Primary Outcome Measures
Name Time Method Calibration of Prospera test for T cell-mediated rejection 18 months Calibration of DD-cfDNA test cut-off values against the probability of T cell-mediated rejection in the biopsy as reported by MMDx.
Calibration of Prospera test for antibody-mediated rejection 18 months Calibration of DD-cfDNA test cut-off values against the probability of antibody-mediated rejection in the biopsy as reported by MMDx.
Calibration of Prospera test for kidney injury 18 months Calibration of DD-cfDNA test cut-off values against the probability of acute and chronic kidney injury in the biopsy as reported by MMDx.
Report calibrated Prospera test results for rejection 6 months Report new DD-cfDNA test cut-off values for rejection
Report calibrated Prospera test results for kidney injury 6 month Report new DD-cfDNA test cut-off values for acute and chronic kidney injury
- Secondary Outcome Measures
Name Time Method Assessment of donor-specific antibody status 6 months Report and compare the DSA status based on centralized and local HLA antibody measurement.
Determine if Prospera blood test can replace kidney biopsy test 6 months Determine if Prospera test, as calibrated by this DD-cfDNA-HLA-MMDx study, will avoid need for indication biopsy when kidney transplant function deteriorates. This will be based on the consensus between participating clinicians.
Trial Locations
- Locations (31)
Tampa General Hospital
🇺🇸Tampa, Florida, United States
University of Maryland School of Medicine
🇺🇸Baltimore, Maryland, United States
The Johns Hopkins University, School of Medicine
🇺🇸Baltimore, Maryland, United States
Detroit Medical Center, Harper University Hospital of Wayne State University
🇺🇸Detroit, Michigan, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Barnes-Jewish Hospital, Washington University at St. Louis
🇺🇸Saint Louis, Missouri, United States
University Hospitals Cleveland Medical Ctr.
🇺🇸Cleveland, Ohio, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Intermountain Transplant Services
🇺🇸Murray, Utah, United States
Virginia Commonwealth University Medical Center
🇺🇸Richmond, Virginia, United States
Division of Nephrology & UW Organ Transplant Center University of Washington
🇺🇸Seattle, Washington, United States
Department of Nephrology, The Royal Melbourne Hospital 1 South East
🇦🇺Melbourne, Australia
University of Alberta, Department of Medicine
🇨🇦Edmonton, Alberta, Canada
ST. Paul's Hospital, 6A Providence Building, 1081 Burrard Street
🇨🇦Vancouver, British Columbia, Canada
University Hospital Merkur Renal Division
🇭🇷Zagreb, Croatia
Institute for Clinical and Experimental Medicine (IKEM)
🇨🇿Prague, Czechia
Charite-Medical University of Berlin Department of Nephrology
🇩🇪Berlin, Germany
Centre of Nephrology, Vilnius University Hospital Santaros Klinikos
🇱🇹Vilnius, Lithuania
Department of Nephrology and Transplantation Medical University in Bialystok
🇵🇱Białystok, Poland
University Hospital nr1 Bydgoszcz, Klinika Transplantologii
🇵🇱Bydgoszcz, Poland
Medical University of Gdańsk Klinika Nefrologii Transplantologii i Chorób Wewnętrznych
🇵🇱Gdańsk, Poland
Medical University of Silesia
🇵🇱Katowice, Poland
Department of Transplantation and General Surgery, Wojewodzki Hospital
🇵🇱Poznań, Poland
Department of Nephrology, Transplantation and Internal Medicine, University Hospital n.2
🇵🇱Szczecin, Poland
Pomeranian Medical University, Samodzielny Publiczny Woj. Szpital Zespolony, Oddzial Nefrologii i Transplantacji Nerek
🇵🇱Szczecin, Poland
Medical University of Warsaw, Department of Transplantation Medicine, Nephrology and Internal Diseases
🇵🇱Warsaw, Poland
Transplant Medicine & Nephrology Clinic, Medical University of Warsaw
🇵🇱Warsaw, Poland
The Children's Memorial Health Institute, Department of Nephrology, Kidney Transplantation and Hypertension
🇵🇱Warsaw, Poland
Wroclaw Medical University, Department of Nephrology and Transplantation Medicine
🇵🇱Wrocław, Poland
Department of Nephrology, University Medical Centre
🇸🇮Ljubljana, Slovenia
University Hospital Zurich
🇨🇭Zürich, Switzerland