Analysis of urinary kidney-specific cell-free DNA in preeclampsia
5 affiliations
- 1Department of Nephrology, Austin Health, Heidelberg, Victoria, Australia
- 2Department of Obstetrics, Mercy Hospital for Women, Heidelberg, Victoria, Australia
- 3Department of Medicine, University of Melbourne, Parkville, Victoria, Australia
- 4Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia
- 5School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, New South Wales, Australia
Abstract
Aim: To assess the feasibility of a novel methodology for quantifying kidney-specific cell-free DNA (ks-cfDNA) and explore whether levels differed between individuals with preeclampsia (PE) and normotensive pregnant controls (NP). Background: Cell-free DNA (cfDNA) is released during cell death and circulates in bodily fluids, including urine. cfDNA quantities reflect the degree of organ injury. As PE is associated with hypertension and kidney injury, we hypothesised that urinary ks-cfDNA would be elevated in PE. Methods: In this single-centre prospective case-control study urine samples were collected from 20 women with PE and 20 NP controls. Digital PCR was used to quantify three kidney-specific epigenetic targets (ks-et): ks-et1 (pan-kidney marker), ks-et2 (renal proximal tubular epithelial cell (RPTEC) and podocyte marker) and ks-et3 (RPTEC marker). The beta-actin gene (ACTB) represented total cfDNA (t-cfDNA). Results: ks-et2 and ks-et3 were higher in the PE group. Median ks-et2 was 231 copies/mL (IQR 65–383) versus 62 copies/mL (IQR 29–215) in NP controls (P = 0.028). Median ks-et3 was 81 copies/mL (IQR 28–199) in PE versus 20 copies/mL (IQR 9–81) for NP participants (P = 0.047). ks-et1 and t-cfDNA showed non-significant increases in PE. Fractional ks-et quantities normalised to t-cfDNA did not differ between groups. Urinary creatinine levels were higher in the PE group (10.9 mmol/L (IQR 4.1–15.3) versus 3.9 mmol/L (IQR 2.3–5.6), P = 0.005). Urine creatinine demonstrated the highest AUC (0.76, 95% CI 0.59–0.92). Conclusion: This exploratory study found that quantification of urinary ks-cfDNA was feasible and that absolute quantities of ks-cfDNA markers ks-et2 and ks-et3 were elevated in PE. Consistent with previous studies, urinary creatinine was a good predictor of PE and outperformed ks-cfDNA in discriminating between preeclamptic and normotensive pregnancies. Further studies are needed to determine the clinical utility and predictive ability of ks-cfDNA in PE.
Related
- Kidzoi Enables Cell-Type-Specific Regulatory Activity and Variant Effect Prediction in Kidney
- Clearance of Strongyloides stercoralis infection using ivermectin improves kidney function and modulates untargeted urinary metabolomic profile in patients with early-stage chronic kidney disease
- Research progress on the epidemiology and diagnostic technologies of urinary tract infections in kidney transplant recipients
- Improving the Diagnosis of Inherited Kidney Diseases Through Domain-Specific Databases
- Free Mitochondrial DNA and Mitophagy Dysfunction in Diabetic Kidney Disease: A Central Mitochondrial-Inflammatory Axis Driving Progressive Renal Injury.
BibTeX
@article{heron2026analysis,
title = {{Analysis of urinary kidney-specific cell-free DNA in preeclampsia}},
author = {Vanessa C. Heron and John B. Whitlam and David H. Murray and Nicky Boulter and Peter Mount and Suet-Wan Choy and Marina Katerelos and Kathy Paizis},
journal = {PLOS One},
year = {2026},
month = sep,
doi = {10.1371/journal.pone.0359105},
url = {https://doi.org/10.1371/journal.pone.0359105},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Analysis of urinary kidney-specific cell-free DNA in preeclampsia
AU - Vanessa C. Heron
AU - John B. Whitlam
AU - David H. Murray
AU - Nicky Boulter
AU - Peter Mount
AU - Suet-Wan Choy
AU - Marina Katerelos
AU - Kathy Paizis
PY - 2026
DA - 2026/09/29
JO - PLOS One
DO - 10.1371/journal.pone.0359105
UR - https://doi.org/10.1371/journal.pone.0359105
AB - Aim: To assess the feasibility of a novel methodology for quantifying kidney-specific cell-free DNA (ks-cfDNA) and explore whether levels differed between individuals with preeclampsia (PE) and normotensive pregnant controls (NP). Background: Cell-free DNA (cfDNA) is released during cell death and circulates in bodily fluids, including urine. cfDNA quantities reflect the degree of organ injury. As PE is associated with hypertension and kidney injury, we hypothesised that urinary ks-cfDNA would be elevated in PE. Methods: In this single-centre prospective case-control study urine samples were collected from 20 women with PE and 20 NP controls. Digital PCR was used to quantify three kidney-specific epigenetic targets (ks-et): ks-et1 (pan-kidney marker), ks-et2 (renal proximal tubular epithelial cell (RPTEC) and podocyte marker) and ks-et3 (RPTEC marker). The beta-actin gene (ACTB) represented total cfDNA (t-cfDNA). Results: ks-et2 and ks-et3 were higher in the PE group. Median ks-et2 was 231 copies/mL (IQR 65–383) versus 62 copies/mL (IQR 29–215) in NP controls (P = 0.028). Median ks-et3 was 81 copies/mL (IQR 28–199) in PE versus 20 copies/mL (IQR 9–81) for NP participants (P = 0.047). ks-et1 and t-cfDNA showed non-significant increases in PE. Fractional ks-et quantities normalised to t-cfDNA did not differ between groups. Urinary creatinine levels were higher in the PE group (10.9 mmol/L (IQR 4.1–15.3) versus 3.9 mmol/L (IQR 2.3–5.6), P = 0.005). Urine creatinine demonstrated the highest AUC (0.76, 95% CI 0.59–0.92). Conclusion: This exploratory study found that quantification of urinary ks-cfDNA was feasible and that absolute quantities of ks-cfDNA markers ks-et2 and ks-et3 were elevated in PE. Consistent with previous studies, urinary creatinine was a good predictor of PE and outperformed ks-cfDNA in discriminating between preeclamptic and normotensive pregnancies. Further studies are needed to determine the clinical utility and predictive ability of ks-cfDNA in PE.
SN - 1932-6203
ER -