GDF-15 and uEGF independently associate with CKD progression in children

Julia Bartels; Mansoureh Tabatabaeifar; Marietta Kirchner; Karolis Ažukaitis; Anke Doyon; Aysun Bayazit; Ali Düzova; Nur Canpolat; Ipek Kaplan Bulut; Lukasz Obrycki; Bruno Ranchin; Rukshana Shroff; Francesca Lugani; Cengiz Candan; Jerome Harambat; Harika Alpay; Mieczyslaw Litwin; Augustina Jankauskienė; Günter Klaus; Dorota Drozdz; Giovanni Montini; Aleksandra Zurowska; Alberto Caldas Afonso; Elke Wühl; Anette Melk; Uwe Querfeld; Otto Mehls; Franz Schaefer

doi:10.1016/j.ekir.2025.07.004

Title	GDF-15 and uEGF independently associate with CKD progression in children
Authors	Bartels, Julia ; Tabatabaeifar, Mansoureh ; Kirchner, Marietta ; Ažukaitis, Karolis ; Doyon, Anke ; Bayazit, Aysun ; Düzova, Ali ; Canpolat, Nur ; Bulut, Ipek Kaplan ; Obrycki, Lukasz ; Ranchin, Bruno ; Shroff, Rukshana ; Lugani, Francesca ; Candan, Cengiz ; Harambat, Jerome ; Alpay, Harika ; Litwin, Mieczyslaw ; Jankauskienė, Augustina ; Klaus, Günter ; Drozdz, Dorota ; Montini, Giovanni ; Zurowska, Aleksandra ; Afonso, Alberto Caldas ; Wühl, Elke ; Melk, Anette ; Querfeld, Uwe ; Mehls, Otto ; Schaefer, Franz
DOI	10.1016/j.ekir.2025.07.004
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Is Part of	Kidney international reports.. New York : Elsevier Inc.. 2025, Early Access, p. [1-10].. ISSN 2468-0249
Keywords [eng]	chronic kidney disease ; CKD progression ; epidermal growth factor ; growth differentiation factor 15 ; pediatric CKD
Abstract [eng]	Introduction Currently, there is limited ability to predict the progression of chronic kidney disease (CKD) in children. Previously we reported that low levels of urinary epidermal growth factor (uEGF) predict CKD progression in children. In the present study, we investigated a novel serum biomarker, growth differentiation factor 15 (GDF-15), in 2 European pediatric CKD cohorts. We additionally explored the combined effect of GDF-15 and/or uEGF on CKD progression in children. Methods The association between serum GDF-15 levels and CKD progression was analyzed in 671 patients of the Cardiovascular Comorbidity in Children with CKD (4C) study, aged 6 to 17 years with an estimated glomerular filtration rate (eGFR) of 10 to 60 ml/min per 1.73 m2 at baseline, and median follow-up of 8 years. The composite end point was start of kidney replacement therapy, 50% eGFR loss, or eGFR < 10 ml/min per 1.73 m2. Results were validated in 329 participants from the ESCAPE trial. Results Higher GDF-15 levels were associated with an increased risk of CKD progression (hazard ratio: 1.40; 95% confidence interval [CI]: 1.10–1.77), independent of age, sex, baseline eGFR, proteinuria, and systolic blood pressure. Whereas adding either GDF-15 or uEGF individually to a model containing these variables improved model fit, combining both markers improved the model further. External validation in the ESCAPE cohort confirmed these results. Conclusion Serum GDF-15 and urine EGF levels may provide complementary information on the risk of CKD progression in children and might be included in future prognostic biomarker panels aimed at personalized, risk-stratified management of pediatric CKD.
Published	New York : Elsevier Inc
Type	Journal article
Language	English
Publication date	2025
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„GDF-15 and uEGF independently associate with CKD progression in children“