a _ Istanbul University, _ Istanbul Faculty of Medicine, Department of Urology, Division of Pediatric Urology, Turkey b _ Istanbul University, _ Istanbul Faculty of Medicine, Department of Biochemistry, Turkey c _ Istanbul University, _ Istanbul Faculty of Medicine, Department of Urology, Turkey * Correspondence to: M. _ Irfan Do ¨nmez, _ Istanbul University, _ Istanbul Faculty of Medicine, Department of Urology, Division of Pediatric Urology, Fatih, C ¸apa, _ Istanbul, 34093, Turkey. Tel.: þ902124142456; fax: þ902126351918. unsalozkuvanci@yahoo.com (U ¨ .O ¨ zkuvancı) m_irfan83@yahoo.com (M. _ Irfan Do ¨ nmez) oziylan@hotmail.com (O. Ziy- lan) tayfunoktar@hotmail.com (T. Oktar) ckucukgergin@yahoo.com (C. Ku ¨c ¸u ¨ kgergin) bilal_cetin@yahoo.com (B. C ¸ etin) erdemselcuk1@gmail.com (S. Erdem) sseckin@istanbul.edu.tr (S ‚ . Sec ¸ kin) Keywords Antenatal; Hydronephrosis; Urinary; Biomarker; Obstruc- tion; Nephropathy Received 20 June 2020 Revised 16 August 2020 Accepted 8 September 2020 Available online xxx Can urinary biomarkers detect obstruction defined by renal functional loss in antenatal hydronephrosis? U ¨ nsal O ¨ zkuvancı a , M. _ Irfan Do ¨nmez a, *, Orhan Ziylan a , Tayfun Oktar a , Canan Ku ¨c ¸u ¨kgergin b , Bilal C ¸etin a , Selc ¸uk Erdem c , S ‚ ule Sec ¸kin b Summary Introduction Diagnosing obstruction and thus, assessment of need for surgery in the management of antenatal hydro- nephrosis may be challenging. Current diagnostic tests are not capable of indicating which patients are at risk for obstructive nephropathy. Biomarkers may play an important role in distinguishing these patients. Objective The aim of this study is to evaluate if urinary bio- markers could differentiate obstruction (OBS) from non-obstructive dilation (NOD) in patients with antenatal hydronephrosis (AH) that underwent pye- loplasty due to loss of differential renal function (DRF). Study design Children with a history of AH and postnatal ante- roposterior (AP) diameter 15 mm were included in this study of prospectively collected data between 2010 and 2018. The OBS group included patients who underwent pyeloplasty due to solely 10% subse- quent decrease in DRF on a MAG-3 scan during follow-up. Patients with stable or improving hydro- nephrosis with no significant reduction in ipsilateral DRF (<10%) during follow-up formed the NOD group. Healthy children with no history of AH and a normal urinary ultrasound were taken as the control group. Urinary IP-10, MCP-1, KIM-1, NGAL, and Ca19-9 levels using ELISA were measured. In the OBS group, urine samples were obtained preoperatively and at 3rd post operative-month whereas in the NOD and control groups, samples were collected at the time of enrollment. Results There were 24 children in the OBS and 27 children in the NOD groups. The control group consisted of 27 healthy children. The pre-operative bladder urine levels of biomarkers of the OBS group were signifi- cantly higher than in the NOD and control group (p < 0.05, for all). In terms of differentiating OBS from NOD, results of ROC analyses for the given cut- off values were as follows: 135.06 ng/mgCr (sensi- tivity 75%; specificity 66%, AUC Z 0.735) for IP-10, 0.89 ng/mgCr (sensitivity 79.2%; specificity 88%, AUC Z 0.802) for KIM-1, 367.65 pg/mgCr (sensitivity 62.5%; specificity 52%, AUC Z 0.660) for MCP-1, 16.15 ng/mgCr (sensitivity 70.8%; specificity 70.4%, AUC Z 0.669) for NGAL, and 55.5 U/mgCr (sensi- tivity 75%; specificity 66%, AUC Z 0.676) for Ca 19-9. Moreover, when KIM-1 was combined with IP-10 and Ca19-9, sensitivity and specificity levels were 83% and 85% (AUC Z 0.919), respectively. Conclusion In this novel study, which focused on scintigraphic DRF loss, KIM-1 was the most successful among all the biomarkers evaluated. Combination of IP-10, Ca19-9 and KIM-1 resulted increased diagnostic ability. Summary Table Overview of all biomarkers. Cut-off value Sensitivity Specificity AUC IP-10 135.0 ng/mgCr 75% 66% 0.735 KIM-1 0.89 ng/mgCr 79.2% 88% 0.802 MCP-1 367.6 pg/mgCr 62.5% 52% 0.660 NGAL 16.1 ng/mgCr 70.8% 70.4% 0.669 Ca 19-9 55.5 U/mgCr 75% 66% 0.676 ROC: Receiver operating characteristics, IP-10: interferon gamma-induced protein 10, MCP-1: monocyte chemotactic protein 1, NGAL: Neutrophil gelatinase-associated lipocalin, KIM-1: kidney injury molecule- 1, Ca 19-9: Carbohydrate antigen 19-9, Cr: creatinine, U: Unit. + MODEL Please cite this article as: O ¨ zkuvancı U ¨ et al., Can urinary biomarkers detect obstruction defined by renal functional loss in antenatal hydronephrosis?, Journal of Pediatric Urology, https://doi.org/10.1016/j.jpurol.2020.09.005 https://doi.org/10.1016/j.jpurol.2020.09.005 1477-5131/ª 2020 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved. Journal of Pediatric Urology (xxxx) xxx xxx