# A Prospective Pilot Study to Investigate Whether Donor‐Derived Cell‐Free DNA Can Be Used as a Biomarker of Recurrent IgA Nephropathy Post–Kidney Transplantation

## TL;DR

This study explores whether donor-derived cell-free DNA can detect IgA nephropathy recurrence after kidney transplants, but finds it less effective than traditional measures like proteinuria.

## Contribution

The study evaluates dd-cfDNA as a non-invasive biomarker for IgAN recurrence post-transplantation in a prospective pilot cohort.

## Key findings

- No significant difference in %dd-cfDNA levels was found between patients with and without IgAN recurrence.
- Proteinuria and eGFR outperformed %dd-cfDNA in detecting IgAN recurrence.
- dd-cfDNA alone may not be a reliable biomarker for IgAN recurrence post-transplantation.

## Abstract

IgA nephropathy (IgAN) is one of the most prevalent glomerulonephropathies and commonly leads to kidney failure. The recurrence of IgAN following transplantation remains a significant concern. Currently, detecting IgAN recurrence requires a kidney biopsy, highlighting the need for non‐invasive biomarkers such as donor‐derived cell‐free DNA (dd‐cfDNA) to aid in early detection. This prospective pilot study aims to evaluate dd‐cfDNA as a non‐invasive biomarker for detecting IgAN recurrence post–kidney transplantation. Specifically, the study seeks to compare %dd‐cfDNA levels in transplanted patients with and without IgAN recurrence and correlate these levels with other kidney function parameters. A total of 32 patients with histologically confirmed IgAN were enrolled, including those with documented IgAN recurrence post‐transplantation and those without recurrence. Plasma samples were collected and processed using the AlloSeq cfDNA kit to quantify relative %dd‐cfDNA levels. Kidney function parameters, including estimated glomerular filtration rate (eGFR) and proteinuria, were also assessed. The study found no significant difference in %dd‐cfDNA levels between transplanted patients with IgAN recurrence and those without recurrence (median 0.37% [IQR 0.28%–3.53%] vs. median 0.42% [IQR 0.15%–0.84%], p = 0.67). Also, %dd‐cfDNA (AUC = 0.57 [95% CI 0.28–0.85], p = 0.64) failed to effectively discriminate IgAN recurrence compared to traditional kidney function parameters such as proteinuria (AUC = 0.96 [95% CI 0.87–1.00], p = 0.002) and eGFR (AUC = 0.74 [95% CI 0.47–1.00], p = 0.09). Relative (%) dd‐cfDNA alone may not be a robust biomarker for detecting IgAN recurrence post‐transplantation. While proteinuria proved a more effective indicator in this study, kidney biopsy remains the gold standard for definitive diagnosis. These findings highlight the challenges of using %dd‐cfDNA as a standalone diagnostic tool for monitoring IgAN recurrence post‐transplantation. Future research should explore larger patient cohorts and longitudinal assessments to refine the utility of dd‐cfDNA and investigate potential combination strategies with other biomarkers.