Can urinary biomarkers detect obstruction defined by renal functional loss in antenatal hydronephrosis?

Abstract

Introduction: Diagnosing obstruction and thus, assessment of need for surgery in the management of antenatal hydronephrosis 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 biomarkers could differentiate obstruction (OBS) from non-obstructive dilation (NOD) in patients with antenatal hydronephrosis (AH) that underwent pyeloplasty due to loss of differential renal function (DRF).

Study design: Children with a history of AH and postnatal anteroposterior (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% subsequent decrease in DRF on a MAG-3 scan during follow-up. Patients with stable or improving hydronephrosis 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 significantly 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 (sensitivity 75%; specificity 66%, AUC = 0.735) for IP-10, 0.89 ng/mgCr (sensitivity 79.2%; specificity 88%, AUC = 0.802) for KIM-1, 367.65 pg/mgCr (sensitivity 62.5%; specificity 52%, AUC = 0.660) for MCP-1, 16.15 ng/mgCr (sensitivity 70.8%; specificity 70.4%, AUC = 0.669) for NGAL, and 55.5 U/mgCr (sensitivity 75%; specificity 66%, AUC = 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 = 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.

Keywords: Antenatal; Biomarker; Hydronephrosis; Nephropathy; Obstruction; Urinary.