Clinical trial NCT05811468: Study Correlation Between Blood, Tissue Gene Expression, Donor Derived Cell Free DNA and Histopathology in Kidney Transplant Recipients
Official title: Pilot Study to Evaluate the Correlation Between Peripheral Gene Expression Profile Testing, Tissue-based Gene Expression Profiling, Donor Derived Cell Free DNA, and Histopathology Among High-risk Kidney Transplant Recipients
Study type: OBSERVATIONAL
Overall status: WITHDRAWN
Conditions: Transplant;Failure,Kidney
Kidney Transplant
Kidney Rejection Transplant
Keywords: Gene expression profile
Molecular microscope
Donor derived cell free DNA
Kidney biopsy
Lead sponsor: Rush University Medical Center
Sponsor class: OTHER
First posted: 2023-04-13
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients undergoing a for cause biopsy due to ongoing or suspected "injury" of the kidney allograft.

Brief summary: This study will compare the performance of Gene Expression Profile (GEP)/ Donor derived cell free deoxyribonucleic acid (dd-cfDNA) tests, to the following tests: Molecular Microscope (MMDx) and histopathology (study of changes in tissues caused by disease) in their ability to diagnose (exactly identify) various types of injury within the transplanted kidney.

Detailed description: This study will evaluate the performance of the blood-based assays like gene expression panel (GEP), and donor derived cell free DNA (dd-cfDNA) against tissue-based assays like molecular microscope (MMDX) and histopathology in their ability to more accurately detect presence of rejection among kidney transplant recipients deemed at higher than usual risk for immunologic injury i.e., rejection.

Furthermore, the study should shed light on the ability of the different blood- based assays to accurately discern between the different types of rejection (early cellular versus humoral) against such confirmed by histopathology and molecular microscope.

The study will also shed light on the ability of these noninvasive biomarkers to be utilized as a tool of immunomodulation in addition to studying their ability to accurately confirm presence of adequately treated rejection among the recipients of kidney transplant.

Eligibility criteria: Inclusion Criteria:

* Patients undergoing a for cause biopsy due to ongoing or suspected "injury" of the allograft.
* Patients will be between 3 months and 7 years post-transplant episode.
* Recipients of both cadaveric and living donor renal transplant are considered eligible.

Exclusion Criteria:

* No multi organ transplant recipients will be included.
* Pregnancy
* HIV positive recipients
* Recipients of kidney transplant from an identical sibling
* Patients with active and biopsy proven BK nephropathy

Primary outcomes:
measure: Quantify the number of rejections in the kidney allograft detected via non invasive blood- based testing as reflected in abnormal laboratory readout of GEP value and dd-CFDNA fraction.
timeFrame: Through study completion, an average of 1 year
measure: Quantify the number of rejection cases detected by histopathology and MMDX as reported by respective pathology laboratories/ pathologists
timeFrame: Through study completion, an average of 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
Study officials:
References:
citation: Gupta G, Moinuddin I, Kamal L, King AL, Winstead R, Demehin M, Kang L, Kimball P, Levy M, Bhati C, Massey HD, Kumar D, Halloran PF. Correlation of Donor-derived Cell-free DNA With Histology and Molecular Diagnoses of Kidney Transplant Biopsies. Transplantation. 2022 May 1;106(5):1061-1070. doi: 10.1097/TP.0000000000003838. Epub 2021 May 28.
citation: Park S, Guo K, Heilman RL, Poggio ED, Taber DJ, Marsh CL, Kurian SM, Kleiboeker S, Weems J, Holman J, Zhao L, Sinha R, Brietigam S, Rebello C, Abecassis MM, Friedewald JJ. Combining Blood Gene Expression and Cellfree DNA to Diagnose Subclinical Rejection in Kidney Transplant Recipients. Clin J Am Soc Nephrol. 2021 Oct;16(10):1539-1551. doi: 10.2215/CJN.05530421.
citation: Bloom RD, Bromberg JS, Poggio ED, Bunnapradist S, Langone AJ, Sood P, Matas AJ, Mehta S, Mannon RB, Sharfuddin A, Fischbach B, Narayanan M, Jordan SC, Cohen D, Weir MR, Hiller D, Prasad P, Woodward RN, Grskovic M, Sninsky JJ, Yee JP, Brennan DC; Circulating Donor-Derived Cell-Free DNA in Blood for Diagnosing Active Rejection in Kidney Transplant Recipients (DART) Study Investigators. Cell-Free DNA and Active Rejection in Kidney Allografts. J Am Soc Nephrol. 2017 Jul;28(7):2221-2232. doi: 10.1681/ASN.2016091034. Epub 2017 Mar 9.
citation: Sigdel TK, Archila FA, Constantin T, Prins SA, Liberto J, Damm I, Towfighi P, Navarro S, Kirkizlar E, Demko ZP, Ryan A, Sigurjonsson S, Sarwal RD, Hseish SC, Chan-On C, Zimmermann B, Billings PR, Moshkevich S, Sarwal MM. Optimizing Detection of Kidney Transplant Injury by Assessment of Donor-Derived Cell-Free DNA via Massively Multiplex PCR. J Clin Med. 2018 Dec 23;8(1):19. doi: 10.3390/jcm8010019.