Demonstrate the relationship between DD-cfDNA levels and HLA antibodies in blood, and the Molecular Microscope® (MMDx) Diagnostic System results in indication biopsies.



Eligible Ages
All ages
Eligible Genders
Accepts Healthy Volunteers

Inclusion Criteria

  • 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.

Exclusion Criteria

  • 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 Model
Time Perspective

Arm Groups

ArmDescriptionAssigned Intervention
Kidney transplant biopsies for cause The study population includes patients with a functioning kidney transplant undergoing a biopsy for clinical indications as standard of care.
  • Diagnostic Test: MMDx
    Portion of kidney transplant indication biopsy
  • Diagnostic Test: Prospera
    Transplant patient blood sample
    Other names:
    • transplant patient blood sample
  • Diagnostic Test: HLA antibody
    Transplant patient blood sample
    Other names:
    • transplant patient blood sample

Recruiting Locations

University of Maryland School of Medicine
Baltimore, Maryland 21201
Raissa Toure

More Details

University of Alberta

Study Contact

Konrad S Famulski, PhD
1 780 492 1725

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 1014 kidney biopsies and corresponding blood samples. Due to considerable interest from participating centers, we extend this study to the total of 1300 biopsies and 3900 blood samples.


Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.