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Kidney Week

Abstract: FR-PO453

Urinary Epidermal Growth Factor as a Prognostic Marker for the Progression in Children with Alport Syndrome

Session Information

Category: Chronic Kidney Disease (Non-Dialysis)

  • 301 CKD: Risk Factors for Incidence and Progression

Authors

  • Li, Baihong, Peking University First Hospital, Beijing, China
  • Ding, Fangrui, Peking University First Hospital, Beijing, China
  • Wang, Fang, Peking University First Hospital, Beijing, China
  • Nair, Viji, University of Michigan, Ann Arbor, Michigan, United States
  • Kretzler, Matthias, University of Michigan, Ann Arbor, Michigan, United States
  • Ju, Wenjun, University of Michigan, Ann Arbor, Michigan, United States
  • Ding, Jie, Peking University First Hospital, Beijing, China
Background

Alport syndrome (AS) is a rare hereditary kidney disease manifested with progressive renal failure, vast majority of the cases are caused by defects in type IV collagen genes. Considerable variation exists in terms of disease progression among patients with AS. Identification of patients at high risk of rapid progression remains an unmet need. Urinary epidermal growth factor has been shown to be independently associated with risk of progression to end stage kidney disease (ESKD) or 40% reduction of baseline eGFR in multiple independent adult CKD cohorts. In this study we aim to assess the prognostic value of uEGF in children with AS.

Methods

117 pediatric patients with AS and 72 healthy children (3-18 year-old) were included in this study. uEGF was measured in duplicates in baseline urine samples using ELISA (R&D) and concentration was normalized by urine creatinine (uEGF/Cr). In patients with longitudinal follow up data (n=38), progression was defined as deteriorated kidney function (CKD stage increase) during follow-up period (average follow-up 29.92±16.18 months). The area under the receiver operating characteristic (ROC) curve was used to assess the discriminative power of the marker.

Results

uEGF/Cr decreases with age in both healthy children and pediatric patients with AS. The decrease rate of uEGF/Cr with age was faster in AS patients. uEGF/Cr is significantly correlated with GFR (r=0.75, p<0.001), after adjustment for age. In 38 patients with longitudinal follow-up, we observed a significant correlation between uEGF and eGFR slope (r=0.58, p<0.001). Patients with lower uEGF/Cr level were at increased risk of progression to a higher CKD stage. uEGF distinguished progressors from patients who do not show CKD stage advance with an AUC of 0.89, versus 0.80 by GFR and 0.79 by ACR.

Conclusion

Our work suggested that uEGF/Cr may be used as a biomarker for accelerated kidney function decline in pediatric patients with AS. It may help to identify patients at high risk of progression for targeted clinical care and improve the patients’stratification in interventional trials. Future validation with more patients and longer follow-up time will be required.

Funding

  • Government Support - Non-U.S.