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Kidney Int. 2019 Mar 20. pii: S0085-2538(19)30184-X. doi: 10.1016/j.kint.2019.01.035. [Epub ahead of print]

Low levels of urinary epidermal growth factor predict chronic kidney disease progression in children.

Author information

1
Clinic of Pediatrics, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania.
2
Department of Internal Medicine/Nephrology, University of Michigan, Ann Arbor, Michigan, USA; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA.
3
Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany.
4
Department of Internal Medicine/Nephrology, University of Michigan, Ann Arbor, Michigan, USA.
5
Department of Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover, Germany.
6
Department of Pediatric Nephrology, Cukurova University, Adana, Turkey.
7
Department of Nephrology, Kidney Transplantation and Arterial Hypertension, The Children`s Memorial Health Institute, Warsaw, Poland.
8
Department of Pediatric Nephrology, Istanbul University Cerrahpasa Faculty of Medicine, Istanbul, Turkey.
9
Division of Pediatric Nephrology, Department of Pediatrics, Ege University Faculty of Medicine, Izmir, Turkey.
10
Division of Pediatric Nephrology, Department of Pediatrics, School of Medicine, Ankara University, Ankara, Turkey.
11
Department of Pediatric Nephrology, University Children's Hospital, Belgrade, Serbia.
12
Department of Pediatrics, Bordeaux University Hospital, Bordeaux, France.
13
Department of Pediatric Nephrology, Marmara University Faculty of Medicine, Istanbul, Turkey.
14
Division of Nephrology, Dialysis, Transplantation, University of Genoa, G. Gaslini Institute, Genoa, Italy.
15
Pediatric Nephrology Unit, Department of Pediatrics, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
16
Department of Pediatric Nephrology, Haseki Educational and Research Hospital, Istanbul, Turkey.
17
Department of Pediatric Nephrology, Bursa Yuksek Ihtisas Teaching and Researching Hospital, Bursa, Turkey.
18
Pediatric Nephrology, Charité Children's Hospital, Berlin, Germany.
19
Pediatric Nephrology, Dialysis and Transplantation Unit, Department of Woman's and Child's Health, University-Hospital of Padova, Padova, Italy.
20
Department of Pediatric Nephrology, Faculty of Medicine, İnönü University, Malatya, Turkey.
21
Department of General Pediatrics, Adolescent Medicine and Neonatology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
22
Department of Pediatric Nephrology, Celal Bayar University, Manisa, Turkey.
23
Department of Pediatric Nephrology, University of Health Sciences, İzmir Tepecik Training and Research Hospital, İzmir, Turkey.
24
Department of Pediatric Nephrology, Charité University, Berlin, Germany.
25
Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, Heidelberg University Hospital, Heidelberg, Germany.
26
Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, Heidelberg University Hospital, Heidelberg, Germany. Electronic address: franz.schaefer@med.uniheidelberg.de.

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.

KEYWORDS:

CKD progression; chronic kidney disease; epidermal growth factor; pediatric CKD

PMID:
31005273
DOI:
10.1016/j.kint.2019.01.035

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