Abstract: FR-PO474

A First Assessment of Urinary Peptide Biomarkers Predictive of Cardiovascular Complications in Children with CKD

Session Information

Category: Chronic Kidney Disease (Non-Dialysis)

  • 303 CKD: Epidemiology, Outcomes - Cardiovascular

Authors

  • Brunchault, Valerie, INSERM U1048, Toulouse, France
  • Buffin-Meyer, Benedicte, INSERM U1048, Toulouse, France
  • Breuil, Benjamin, INSERM U1048, Toulouse, France
  • Magalhães, Pedro, Mosaiques Diagnostics GmbH, Hannover, Germany
  • Zürbig, Petra, Mosaiques Diagnostics GmbH, Hannover, Germany
  • Kunzmann, Kevin, Institute of Medical Biometry and Informatics, Heidelberg University, Heidelberg, Germany
  • Schaefer, Franz S., University of Heidelberg, Heidelberg, BW, Germany
  • Schanstra, Joost, INSERM U1048, Toulouse, France
  • Klein, Julie, INSERM U1048, Toulouse, France

Group or Team Name

  • 4C study consortium
Background

Cardiovascular disease (CVD) is the most important comorbidity affecting long-term survival in children and young adults with CKD. CVD is usually subclinical and early detection of pediatric CKD patients with high risk to develop CVD would be optimal. Our objective was to explore the urinary peptidome for biomarkers for early prognosis of CVD in children with CKD.

Methods

In this preliminary study, we used 86 pediatric patients from the Cardiovascular Comorbidity in Children with CKD (4C) cohort, which consists of children (6-17 years) with advanced CKD (eGFR=10–45 ml/min/1.73 m2). During a 3-year follow-up, the carotid intima-media thickness (cIMT), pulse wave velocity (PWV) and left ventricular mass index (LVMI) were measured annually as surrogate markers of CVD complications. For each marker, the slope was calculated as a measure of CVD progression. Urine at baseline was analyzed by capillary-electrophoresis coupled to mass spectrometry for the identification of urinary peptides associated to progression of CVD.

Results

Among 7586 urinary peptides, 190, 22 and 14 urinary peptides were associated to progression of cIMT, PWV and LVMI, respectively (p<0.05). These peptides were combined in mathematical models to build the cIMT190P, PWV22P and LVMI14P classifiers. These classifiers were then validated using an independent validation cohort. The cIMT190P classifier predicted cIMT progression with 80% sensitivity [95% CI, 44.4 to 97.5], 100% specificity (95% CI, 66.4 to 100) and an area under the ROC curve (AUC) of 0.87 (95% CI, 0.68 to 1.00). The PWV22P classifier predicted PWV progression with 83% sensitivity (95% CI, 51.6 to 97.9), 70% specificity (95% CI, 34.8 to 93.3) and an AUC of 0.83 (95% CI, 0.64 to 1.00). However, the LVMI classifier was not validated.

Conclusion

These results indicate that urinary peptides could be used as a non-invasive tool for the early prediction of CVD complications associated to CKD in children. An additional 250 patients from the 4C study will now be used to refine and confirm these results. [Equal contribution JPS and JK]

Funding

  • Government Support - Non-U.S.