Urine Cell-Free RNA versus Plasma Cell-Free RNA for Monitoring of Immune and Urinary Tract Complications

While it is well known that cell-free RNA (cfRNA) can be isolated from urine, the diagnostic potential of this urine cfRNA, especially in comparison to plasma cfRNA, remains underexplored. Here, we directly compared the utility of urine cfRNA and plasma cfRNA for the monitoring of systemic and urinary tract related complications. We analyzed 297 matched plasma and urine cfRNA isolates obtained from three cohorts of patients: Hematopoietic Stem Cell Transplant (HSCT) recipients, patients with acute kidney injury (AKI), and healthy volunteers. The data highlight the unique cellular origins and properties of urinary and plasma RNA. Most importantly, we find that although plasma cfRNA is a superior analyte for monitoring immune and systemic complications, urinary cfRNA is more sensitive to complications of the urinary tract, including cell-type specific injury in the kidney. These findings highlight the potential of urine cfRNA as a novel analyte in diagnostic medicine.