502 - Utilization of donor-derived cell free DNA in pediatric kidney transplantation: results from the NAPRTCS registry centers

Publication Number: 2488.502

Olga Charnaya, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Sara Boynton, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Dechu Puliyanda, Cedars Sinai Guerin Childrens, Los Angeles, CA, United States; Priya S. Verghese, Northwestern University The Feinberg School of Medicine, Chicago, IL, United States; Vaishali Singh, Medical College of Wisconsin, Wauwatosa, WI, United States; Vikas Dharnidharka, Rutgers, Robert Wood Johnson Medical School, New Brunswick, NJ, United States

Background: Serum creatinine, the most common biomarker to detect acute rejection (AR), is neither sensitive enough nor is the rise early enough, to prevent significant acute rejection-induced damage. Peripheral blood dd-cfDNA percentage has been identified as a biomarker for allograft injury in adults, but studies in large generalizable cohorts of children are lacking. The North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS), is a voluntary multi-center consortium that has been collecting data on children and young adults with kidney transplants since 1987, and therefore is the ideal registry to study the use and effectiveness of dd-cfDNA in pediatric patients.

Objective: Characterize the use of dd-cfDNA testing at NAPRTCS centers and describe the diagnostic accuracy for detection of acute rejection and BK nephropathy.

Design/Methods: In addition to the routine transplant data collected by NAPRTCS every 6 months (e.g. recipients demographics, donor characteristics, immunosuppression, graft function, and rejection) dd-cfDNA results obtained as part of standard of care, whether for surveillance or for-cause, were collected since 2022. Centers indicated which assay was used (Prospera vs Allosure vs Other), and whether the test was associated with a biopsy or an episode of AR.

Results: As of December 31, 2024 we have collected data on 2324 samples from 314 distinct patients with 223 associated biopsies. The cohort consists of patients that are mean age 10 year [SD 5.6], 59% male, 65% White race, and 44% with CAKUT/obstructive etiology of kidney failure. Most patients (53.5%) received a kidney from a deceased donor source and had dd-cfDNA testing utilizing an Allosure platform (88%). The incidence of rejection in the cohort was 10.8%. The 1286 Allosure tests in the cohort had good specificity (89% for dd-cfDNA > 1%) but poor sensitivity (42%) for detection of AR, Figure 1. Comparatively, serum creatinine had better sensitivity (79% for creatinine change > 25%) but very low specificity (14.6%). The combination of Allosure >1% and creatinine > 25% had improved positive predictive value over either test alone. Allosure > 1% can also be seen in incidences of BK nephropathy and in our cohort, there was good specificity for this finding. For acute rejection and BK nephropathy the negative predictive value was 98% and 91%, respectively.

Conclusion(s): The dd-cfDNA is elevated in the setting of acute rejection and BK nephropathy and has excellent specificity and negative predictive value for ruling-out rejection and BK nephropathy. Biopsy is still needed to confirm and characterize rejection.

Figure 1
Diagnostic accuracy of dd-cfDNA and creatinine for detection of biopsy-proven acute rejection, and the diagnostic accuracy of dd-cfDNA for detection of BK nephropathy.