ESPN 51th Annual Meeting

ESPN 2018

Urinary Epidermal Growth Factor (uEGF) Improves Prediction of Chronic Kidney Disease (CKD) Progression in Children
KAROLIS AZUKAITIS 1 Wenjun Ju 2 Marietta Kirchner 3 Michelle Smith 2 Viji Nair 2 Zhiyin Fang 2 Daniela Thurn-Valsassina 4 Aysun Bayazit 5 Anna Niemirska 6 Nur Canpolat 7 Ipek Kaplan Bulut 8 Fatos Yalcinkaya 9 Dusan Paripovic 10 Jerome Harambat 11 Nilgun Cakar 9 Harika Alpay 12 Francesca Lugani 13 Francesca Mencarelli 14 Mahmut Civilibal 15 Hakan Erdogan 16 Jutta Gellermann 17 Enrico Vidal 18 Yilmaz Tabel 19 Charlotte Gimpel 20 Pelin Ertan 21 Onder Yavascan 22 Anette Melk 4 Uwe Querfeld 23 Matthias Kretzler 2 Franz Schaefer 24

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

Urinary EGF, a presumed marker of tubulointerstitial injury, has been recently shown to predict CKD progression in adults with glomerular CKD. The performance of uEGF in the predominantly non-glomerular spectrum of pediatric CKD is unknown.

Material and methods:

Post-hoc analysis of the Cardiovascular Comorbidity in Children with Chronic Kidney Disease (4C) study that prospectively follows children aged 6-17 years with CKD stages 3-5. Urinary EGF was measured in spot urine samples collected within 6 months of enrollment and was normalized to urine creatinine (uEGF/Cr). The primary endpoint of CKD progression was defined as a composite of 50% decline in baseline eGFR, eGFR < 15 ml/min/1.73 m2 or start of renal replacement therapy. Cox regression and C-statistic were employed to determine the predictive value of uEGF.


623 children (12.2±3.35 years) with median baseline eGFR of 28.1 (21.6-35.4) ml/min/1.73 m2 were included. The predominant renal diagnosis was congenital anomalies of kidney and urinary tract (69.8%). 288 (46.2%) patients reached the composite endpoint accounting for 15.1 events/100 patient years.  In the multivariable analysis, higher uEGF levels were associated with higher eGFR and proteinuria, and younger age (all p<0.0001), but not renal diagnosis or serum bicarbonate.  When added to a model with age, sex, baseline eGFR, proteinuria, systolic blood pressure and renal diagnosis, uEGF/Cr was significantly associated with lower risk of CKD progression (HR 0.76, 95% CI [0.69, 0.84]). The addition of uEGF/Cr to the model also improved discrimination of risk for CKD progression at years 1, 2 and 3 (C-statistic 0.843 to 0.857, 0.814 to 0.827 and 0.799 to 0.81, respectively).


Urinary EGF is associated with and improves the prediction of CKD progression in the pediatric population with predominantly non-glomerular CKD. Our results expand the findings from adult cohorts to the entire spectrum of glomerular and non-glomerular CKD.