Donor-Derived Cell-Free DNA Levels Risk-Stratify Polyoma BK Viremia and Associated Clinical Events After Kidney Transplantation – Preliminary Results from ADMIRAL Study
1University of Texas McGovern Medical School, Houston, TX, 2University of Minnesota, Minneapolis, MN, 3University of Maryland School of Medicine, Baltimore, MD, 4Virginia Commonwealth University, Richmond, VA, 5Washington University in St. Louis, St. Louis, MO, 6Tampa General Hospital, Tampa, FL, 7CareDx, Brisbane, CA, 8University of Colorado, Aurora, CO, 9Intermountain Medical Center, Murray, UT
Meeting: 2021 American Transplant Congress
Abstract number: 268
Keywords: Kidney transplantation, Non-invasive diagnosis, Polyma virus
Topic: Clinical Science » Infectious Disease » Kidney: Polyoma
Session Information
Session Name: BK virus in Kidney Recipients
Session Type: Rapid Fire Oral Abstract
Date: Monday, June 7, 2021
Session Time: 6:00pm-7:00pm
Presentation Time: 6:15pm-6:20pm
Location: Virtual
*Purpose: The threshold of 10,000 copies for blood Quant BK PCR has been used as a surrogate for BK nephropathy (BKN) in kidney transplant recipients (KTR) and affects treatment decisions. We hypothesized that patients with BK viremia are heterogeneous in terms of clinical outcomes and may be optimally stratified when also assessing donor-derived cell-free DNA (dd-cfDNA) levels.
*Methods: 883 visits from 246 patients were examined from the Assessing dd-cfDNA monitoring insights of renal allograft with longitudinal surveillance (ADMIRAL study; clinicaltrials.gov: NCT04566055219). All patients had dd-cfDNA (AlloSure®; CareDx) with standard post-transplant surveillance. All clinical events and BK Quant PCR were assessed. A high dd-cfDNA level was defined as >0.5% based on previous injury analysis in the ADMIRAL cohort.
*Results: The distribution of BK PCR viral load demonstrated that majority of KTR were assessed as asymptomatic. In ADMIRAL (FIGURE 1), 96.5% of viremia KTR had Quant PCR < 10,000 copies and 3.5% >10,000 copies. No significant association was observed between dd-cfDNA and the PCR-based dichotomized BK classes (Kruskal-Wallis p-value:0.4237). No significant correlation was observed between dd-cfDNA levels and PCR copies (R:0.0088). However within this cohort of <10,000 copies, patients with elevated dd-cfDNA (>0.5%) levels had increased incidences for DSA (HLA) and allograft rejection (ABMR and TCMR) based on histopathology results (FIGURE2).
*Conclusions: The utility of dd-cfDNA as a decision supporting tool, when modulating immunosuppression in response to the BK PCR magnitude, may provide benefit for detecting rejection. Higher levels of dd-cfDNA in the context of BK viremia are associated with increases of other adverse events, suggesting that BK PCR copies alone are insufficient to risk-stratify the severity of BKV graft injury. dd-cfDNA does not correlate with BK PCR copies and so provides additive information to interpretation.
To cite this abstract in AMA style:
Pai A, Bu L, Bromberg JS, Gupta G, Moinuddin I, Alhamad T, Bowers V, Ghosh S, Tian W, Stites E, Anand S. Donor-Derived Cell-Free DNA Levels Risk-Stratify Polyoma BK Viremia and Associated Clinical Events After Kidney Transplantation – Preliminary Results from ADMIRAL Study [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/donor-derived-cell-free-dna-levels-risk-stratify-polyoma-bk-viremia-and-associated-clinical-events-after-kidney-transplantation-preliminary-results-from-admiral-study/. Accessed December 11, 2024.« Back to 2021 American Transplant Congress