# Donor-Derived Cell-Free DNA in Pancreas-Kidney, Heart-Kidney, and Liver-Kidney Multiorgan Transplant Recipients (MOTR)

## TL;DR

This study examines donor-derived cell-free DNA levels in multi-organ transplant recipients to understand how they compare to single-organ transplants and their potential for detecting organ rejection.

## Contribution

The study provides the largest multi-center analysis of dd-cfDNA in multi-organ transplant recipients, revealing organ-specific patterns.

## Key findings

- Median dd-cfDNA levels in heart-kidney recipients were significantly higher than in heart-only recipients.
- Liver-kidney recipients had significantly higher dd-cfDNA levels compared to kidney-only recipients.
- dd-cfDNA levels were associated with organ impairment markers like elevated pancreatic and liver enzymes.

## Abstract

Donor-derived cell free DNA (dd-cfDNA) is an established biomarker for detection of rejection in single organ transplants; data is limited in multi-organ transplant (MOT) recipients. “Use of dd-cfDNA in Multi-Organ Transplant Recipients” (MOTR) was a multicenter, prospective, cross-sectional study that assessed dd-cfDNA fraction (%) and donor quantity score (DQS, cp/mL) in pancreas-kidney (PKT), heart-kidney (HKT), and liver-kidney (LKT) recipients. We explored dd-cfDNA baseline levels across the different organ combinations, and compared them to kidney-only (KT) and heart-only (HT) transplant recipients. Among 347 MOT recipients from 18 sites (PKT = 183, HKT = 57, LKT = 107), most (88.2%) had simultaneous transplants. Median dd-cfDNA levels in PKT and HKT recipients were not significantly different from KT; median dd-cfDNA levels among HKT recipients were significantly higher than in HT recipients (p < 0.001). In LKT recipients, median dd-cfDNA was significantly higher compared to KT (p < 0.001). dd-cfDNA showed associations with organ impairment indicated by abnormal values of pancreatic and liver enzymes in PKT and LKT. As the largest multi-center study to date evaluating dd-cfDNA levels in MOT recipients, MOTR showed that organ-specific physiology affects dd-cfDNA levels across organ transplant combinations, laying the foundation for future efforts to use dd-cfDNA to assess organ-specific signatures of allograft injury in MOT recipients.

Box plot of findings shows dd-cfDNA percentages for various transplant parings: Displays study cohort: pancreas-kidney (n=183), liver-kidney (n=107), heart-kidney (n=57). Box plot of dd-cfDNA findings shows percentages for various transplants: single (KT, HT) and multi-organ (SPKT, SHKT, SLKT). Includes dd-cfDNA testing method and associations with high-risk organ injury signals like increased amylase, lipase, ALT, AST, ALP. Published by Gupta G et al., Transpl. Int. 2025.