JMIR Publications

ABSTRACT

Background:

Kidney transplant provides survival benefits to many patients in end stage renal failure. Advancements in medicine and technology have provided significant improvements in short term outcomes; however, long term outcomes are still lacking. Early events such as the diagnosis and treatment of subclinical rejection can modify the course of events and contribute to better long- term survival. Non-invasive blood-based biomarkers provide opportunity to aid in early diagnosis of subclinical rejection and allow for earlier intervention.

Objective:

The aim of this study is to evaluate long term clinical outcomes in kidney transplant patients undergoing non-invasive rejection monitoring with the OmniGraf® biomarker panel (TruGraf® and TRAC™)

Methods:

The TRULO (TruGraf Long-term Clinical Outcomes) study is a prospective, multi-center, observational study evaluating quarterly surveillance and additional testing when rejection is suspected (for cause) with the OmniGraf biomarker panel, which includes both TruGraf® Gene Expression Profile and TRAC™ donor-derived cell free DNA (dd-cfDNA). The TruGraf test is a qualitative, “rule out” assay that confirms if a patient’s peripheral gene expression is similar to a biopsy confirmed phenotype of no rejection (immune quiescence). TRAC™ dd-cfDNA utilizes single nucleotide polymorphisms (SNPs) present in genes of the organ donor compared to the recipient to estimate the fraction of circulating cfDNA originating from donor. Recent data support that utilizing a combination of gene expression and dd-cfDNA may be complementary in aiding the diagnosis of subclinical rejection. The TRULO study will collect data over a 2-year study period with 2000 subjects at about 50 US transplant centers. The primary end point is a composite of the occurrence of either biopsy proven acute rejection (on a for cause biopsy) OR a decrease from baseline in eGFR >10ml/min at 2-years post-enrollment. A key secondary endpoint is the evaluation of the clinical utility surveys performed with each set of TruGraf and TRAC results.

Results:

Enrollment is competitive with 50 total enrolling sites. As of July 2022, 1324 patients have been enrolled with data collection in process.

Conclusions:

There is a need for laboratory monitoring specific for immune status and rejection risk, in particular subclinical rejection that occurs prior to a rise in serum creatinine. TRULO aims to evaluate long term clinical outcomes in kidney transplant patients undergoing non-invasive rejection monitoring with the OmniGraf® biomarker panel.