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Kidney InternationalVolume 96, Issue 1, July 2019, Pages 214-221

Low levels of urinary epidermal growth factor predict chronic kidney disease progression in children(Article)(Open Access)

  • Azukaitis, K.,
  • Ju, W.,
  • Kirchner, M.,
  • Nair, V.,
  • Smith, M.,
  • Fang, Z.,
  • Thurn-Valsassina, D.,
  • Bayazit, A.,
  • Niemirska, A.,
  • Canpolat, N.,
  • Bulut, I.K.,
  • Yalcinkaya, F.,
  • Paripovic, D.,
  • Harambat, J.,
  • Cakar, N.,
  • Alpay, H.,
  • Lugani, F.,
  • Mencarelli, F.,
  • Civilibal, M.,
  • Erdogan, H.,
  • Gellermann, J.,
  • Vidal, E.,
  • Tabel, Y.,
  • Gimpel, C.,
  • Ertan, P.,
  • Yavascan, O.,
  • Melk, A.,
  • Querfeld, U.,
  • Wühl, E.,
  • Kretzler, M.,
  • Schaefer, F.,
  • Arbeiter, K.,
  • Rosales, A.,
  • Dusek, J.,
  • Zaloszyc, A.,
  • Liebau, M.,
  • Weber, L.,
  • Muschiol, E.,
  • Büscher, R.,
  • Oh, J.,
  • Thurn-Valassina, D.,
  • Haffner, D.,
  • John, U.,
  • Wygoda, S.,
  • Jeck, N.,
  • Wigger, M.,
  • Testa, S.,
  • Murer, L.,
  • Matteucci, C.,
  • Jankauskiene, A.,
  • Drozdz, D.,
  • Zurowska, A.,
  • Zaniew, M.,
  • Litwin, M.,
  • Nimierska, A.,
  • Teixeira, A.,
  • Peco-Antic, A.,
  • Laube, G.,
  • Anarat, A.,
  • Duzova, A.,
  • Bilginer, Y.,
  • Caliskan, S.,
  • Mir, S.,
  • Sözeri, B.,
  • Kranz, B.,
  • Dorn, B.,
  • Baskin, E.,
  • Soylemezoglu, O.,
  • Emre, S.,
  • Candan, C.,
  • Kiyak, A.,
  • Ozcelik, G.,
  • Shroff, R.,
  • Rachin, B.,
  • Szczepanska, M.,
  • Donmez, O.,
  • Balat, A.,
  • Aksu, N.,
  • Yilmaz, E.,
  • Bakkaloglu, A.,
  • Ozaltin, F.,
  • Sallay, P.,
  • Drożdż, D.,
  • Bonzel, K.-E.,
  • Wingen, A.-M.,
  • Balasz, I.,
  • Trivelli, A.,
  • Perfumo, F.,
  • Müller-Wiefel, D.-E.,
  • Möller, K.,
  • Offner, G.,
  • Enke, B.,
  • Hadtstein, C.,
  • Mehls, O.,
  • Hohbach-Hohenfellner, K.,
  • Jeck, N.,
  • Klaus, G.,
  • Ardissino, G.,
  • Montini, G.,
  • Charbit, M.,
  • Niaudet, P.,
  • Afonso, A.C.,
  • Fernandes-Teixeira, A.,
  • Dušek, J.,
  • Picca, S.,
  • Berg, U.B.,
  • Celsi, G.,
  • Fischbach, M.,
  • Terzic, J.,
  • Fydryk, J.,
  • Urasinski, T.,
  • Coppo, R.,
  • Peruzzi, L.,
  • Grenda, R.,
  • Neuhaus, T.J.,
  • 4C Study
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  • aClinic of Pediatrics, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
  • bDepartment of Internal Medicine/Nephrology, University of Michigan, Ann Arbor, MI, United States
  • cDepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, United States
  • dInstitute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany
  • eDepartment of Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover, Germany
  • fDepartment of Pediatric Nephrology, Cukurova University, Adana, Turkey
  • gDepartment of Nephrology, Kidney Transplantation and Arterial Hypertension, The Children`s Memorial Health Institute, Warsaw, Poland
  • hDepartment of Pediatric Nephrology, Istanbul University Cerrahpasa Faculty of Medicine, Istanbul, Turkey
  • iDivision of Pediatric Nephrology, Department of Pediatrics, Ege University Faculty of Medicine, Izmir, Turkey
  • jDivision of Pediatric Nephrology, Department of Pediatrics, School of Medicine, Ankara University, Ankara, Turkey
  • kDepartment of Pediatric Nephrology, University Children's Hospital, Belgrade, Serbia
  • lDepartment of Pediatrics, Bordeaux University Hospital, Bordeaux, France
  • mDepartment of Pediatric Nephrology, Marmara University Faculty of Medicine, Istanbul, Turkey
  • nDivision of Nephrology, Dialysis, Transplantation, University of Genoa, G. Gaslini Institute, Genoa, Italy
  • oPediatric Nephrology Unit, Department of Pediatrics, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
  • pDepartment of Pediatric Nephrology, Haseki Educational and Research Hospital, Istanbul, Turkey
  • qDepartment of Pediatric Nephrology, Bursa Yuksek Ihtisas Teaching and Researching Hospital, Bursa, Turkey
  • rPediatric Nephrology, Charité Children's Hospital, Berlin, Germany
  • sPediatric Nephrology, Dialysis and Transplantation Unit, Department of Woman's and Child's Health, University-Hospital of Padova, Padova, Italy
  • tDepartment of Pediatric Nephrology, Faculty of Medicine, İnönü University, Malatya, Turkey
  • uDepartment of General Pediatrics, Adolescent Medicine and Neonatology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
  • vDepartment of Pediatric Nephrology, Celal Bayar University, Manisa, Turkey
  • wDepartment of Pediatric Nephrology, University of Health Sciences, İzmir Tepecik Training and Research Hospital, İzmir, Turkey
  • xDepartment of Pediatric Nephrology, Charité University, Berlin, Germany
  • yDivision of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, Heidelberg University Hospital, Heidelberg, Germany

Abstract

Urinary epidermal growth factor (uEGF) has recently been identified as a promising biomarker of chronic kidney disease (CKD) progression in adults with glomerular disease. Low levels of uEGF predict CKD progression and appear to reflect the extent of tubulointerstitial damage. We investigated the relevance of uEGF in pediatric CKD. We performed a post hoc analysis of the Cardiovascular Comorbidity in Children with CKD (4C) study, which prospectively follows children aged 6–17 years with baseline estimated glomerular filtration rate (eGFR) of 10–60 ml/min/1.73 m2. uEGF levels were measured in archived urine collected within 6 months of enrollment. Congenital abnormalities of the kidney and urinary tract were the most common cause of CKD, with glomerular diseases accounting for <10% of cases. Median eGFR at baseline was 28 ml/min/1.73 m2, and 288 of 623 participants (46.3%) reached the composite endpoint of CKD progression (50% eGFR loss, eGFR < 10 ml/min/1.73 m2, or initiation of renal replacement therapy). In a Cox proportional hazards model, higher uEGF/Cr was associated with a decreased risk of CKD progression (HR 0.76; 95% CI 0.69–0.84) independent of age, sex, baseline eGFR, primary kidney disease, proteinuria, and systolic blood pressure. The addition of uEGF/Cr to a model containing these variables resulted in a significant improvement in C-statistics, indicating better prediction of the 1-, 2- and 3-year risk of CKD progression. External validation in a prospective cohort of 222 children with CKD demonstrated comparable results. Thus, uEGF may be a useful biomarker to predict CKD progression in children with CKD. © 2019 International Society of Nephrology

Author keywords

chronic kidney diseaseCKD progressionepidermal growth factorpediatric CKD

Indexed keywords

EMTREE drug terms:epidermal growth factorbiological markerepidermal growth factor
EMTREE medical terms:adolescentArticlechildchronic kidney failurecohort analysiscomorbiditycontrolled studydisease courseestimated glomerular filtration ratefemalehumanmajor clinical studymalepost hoc analysispredictionpriority journalprospective studyprotein functionproteinuriarenal replacement therapyrisk factorsystolic blood pressureurinalysisagechronic kidney failuredisease exacerbationfollow upglomerulus filtration ratepathologypathophysiologyphysiologypredictive valueurine
MeSH:AdolescentAge FactorsBiomarkersChildDisease ProgressionEpidermal Growth FactorFemaleFollow-Up StudiesGlomerular Filtration RateHumansMalePredictive Value of TestsProspective StudiesRenal Insufficiency, ChronicRenal Replacement TherapyRisk Factors

Chemicals and CAS Registry Numbers:

epidermal growth factor, 59459-45-9, 62229-50-9;

Biomarkers; Epidermal Growth Factor

Funding details

Funding sponsor Funding number Acronym
Seventh Framework Programme2012-305608FP7
Seventh Framework ProgrammeFP7
Bundesministerium für Bildung und Forschung01EO0802BMBF
Bundesministerium für Bildung und ForschungBMBF
Seventh Framework ProgrammeFP7
KfH-Stiftung Präventivmedizin
European Renal Association-European Dialysis and Transplant AssociationERA-EDTA

  • 1

    Support for the 4C Study was received from the ERA-EDTA Research Programme, the KfH Foundation for Preventive Medicine, and the German Federal Ministry of Education and Research (reference number: 01EO0802). FS and MK received support for this study from the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement No. 2012-305608 (EURenOmics). FS, EW, FL, EV, and AM are members of the European Reference Network for Rare Kidney Diseases (ERKNet).

  • 2

    Support for the 4C Study was received from the ERA-EDTA Research Programme, the KfH Foundation for Preventive Medicine, and the German Federal Ministry of Education and Research (reference number: 01EO0802). FS and MK received support for this study from the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement No. 2012-305608 (EURenOmics). FS, EW, FL, EV, and AM are members of the European Reference Network for Rare Kidney Diseases (ERKNet).

  • ISSN: 00852538
  • CODEN: KDYIA
  • Source Type: Journal
  • Original language: English
  • DOI: 10.1016/j.kint.2019.01.035
  • PubMed ID: 31005273
  • Document Type: Article
  • Publisher: Elsevier B.V.

  Schaefer, F.; Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, Im Neuenheimer Feld 430, Heidelberg, Germany;
© Copyright 2021 Elsevier B.V., All rights reserved.

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