Increases in donor-derived cell-free DNA prior to biopsy proven rejection in kidney transplant

Document Type

Conference Proceeding

Publication Date

9-1-2024

Publication Title

Transplantation

Keywords

circulating free DNA, adult, Caucasian, clinical trial, cohort analysis, conference abstract, creatinine blood level, diagnosis, female, graft recipient, human, human tissue, kidney allograft rejection, kidney graft, major clinical study, male, proteinuria

Abstract

Introduction: The most common clinical indicators for kidney allograft rejection include serum creatinine and proteinuria. Unfortunately, both are lagging indicators that increase once injury has already occurred. Donor-derived cell-free DNA (dd-cfDNA) has been validated as a marker for detection of allograft active rejection (AR) in kidney transplant recipients as well as other solid organ transplants. We sought to test whether dd-cfDNA is a leading indicator of rejection in kidney transplant recipients (KTR). Method: KTR with a biopsy (Bx) and >1 dd-cfDNA tests in the six months prior to the Bx from a 1,631 patient interim analysis cohort of the ProActive registry study (ClinicalTrials.gov NCT04091984) were included. Dd-cfDNA results (the ProsperaTM test) and serum creatinine (SCr) results were grouped by time prior to biopsy and stratified by ultimate Bx finding: ABMR, TCMR, and non-rejection. Results: 424 patients had a Bx and >1 dd-cfDNA result (1,013 total) drawn 0-180 days prior to Bx. 94.5% of dd-cfDNA tests (958/1,013) had a matched SCr test performed at the same visit. The cohort was 59.9% male, 52.1% white and had a median age of 52.0 years. Clinical Bx diagnoses included 26 ABMR, 62 TCMR, and 336 non-rejection. Median dd-cfDNA fraction (dd-cfDNA%) was significantly elevated five months prior to an ABMR Bx and two months prior to a TCMR Bx, compared to non-rejection (Figure 1A). SCr levels were not significantly elevated at any time point prior to Bx in cases with rejection (Figure 1B). Of the 336 patients with a non-rejection Bx, 11.3% (n=38) subjects had one increased dd-cfDNA test result (defined as >1%), and 5.3% (n=18) had two or more increased dd-cfDNA test results during the 6 month period prior to Bx. At the time of a non-rejection Bx, the median eGFR was significantly lower in patients with two or more prior increased dd-cfDNA test results (45.4 [30.5-52.6]) compared to patients with either zero (58.5 [47.2-72.4]) (p=0.00018), or one prior increased dd-cfDNA test result (60.2 [48.3-72.0]) (p=0.0006) (Figure 2). Conclusion: These data support the hypothesis that dd-cfDNA% is a leading indicator of rejection, and was elevated up to five months prior to a biopsy proven ABMR rejection and two months prior to a biopsy proven TCMR rejection. In patients with a non-rejection biopsy, increased ddcfDNA was significantly associated with reduced eGFR. Earlier detection of AR by dd-cfDNA may allow for earlier treatment of rejection. (Figure Presented).

Volume

108

Issue

9S

First Page

277

Last Page

278

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