Urine Biomarkers Combined With Ultrasound for the Diagnosis of Obstruction in Pediatric Hydronephrosis

Abstract

Introduction: To establish the efficacy of ultrasound (US) combined with urine biomarkers in differentiating patients who require surgical management from those who do not, avoiding invasive investigations. Materials and Methods: From February 2019 to February 2021, all pediatric patients who presented with hydronephrosis were selected for the study. All renal units (RU) were evaluated by US, and fresh frozen voided urine samples were collected at the time of inclusion. Hydronephrosis grade was evaluated by the Society for Fetal Urology (SFU) and an alternative grading system (AGS). Patients who had high-grade hydronephrosis on US were referred to renal scan (RS) or intervention, when there was an increase of dilatation in subsequent follow-up images. Fresh frozen urine from the control group with no history of renal diseases and no renal anomalies on US was collected. We compared differences of US parameters combined with urine biomarkers between surgically and non-surgically managed patients and between the groups of patients when they were stratified by different RS findings and analyzed whether urinary biomarkers give any additional value to US. Instead of the anterior-posterior diameter (APD), we used its ratio with mid-parenchymal thickness. The additional efficacy of biomarkers to US was calculated when the US component was derived to a cumulative APD/mid-parenchymal ratio. Results: Sixty-four patients with hydronephrosis were prospectively included in the study accounting for a total of 81 patient visits and 162 RUs evaluated. A control group of 26 patients was collected. The mean age at inclusion in the hydronephrosis group was 43.7(±45.5) months, and a mean age in a control group was 61.2(±41.3) months. The cumulative APD/mid-parenchymal ratio combined with urinary albumin, β2 microglobulin (β2-M), and urinary neutrophil gelatinase-associated lipocalcin may have a better performance in the prediction of surgical intervention than the cumulative APD/mid-parenchymal ratio alone (p = 0.1). The best performance to detect the increased tissue transit time and obstructive curve on RS was demonstrated by the β2-M creatinine ratio. An increased cumulative APD/mid-parenchymal ratio with biomarkers together had a fairly good sensitivity and specificity for detection of DRF < 40%. Conclusions: According to our data, the APD/mid-parenchymal ratio alone has good efficacy in prediction of surgery and abnormal RS findings especially when combined with urine biomarkers.

Keywords: hydronephrosis; renal scan; ultrasound; ureteropelvic junction obstruction; urine biomarkers.

Figure 1

(A) ROC curve APD/mid-parenchymal ratio with a cutoff value for operation of 1.51 (p < 0.001). The odds ratio for operation when the APD/mid-parenchymal ratio is more than the cutoff (95% CI) is 1.97 (1.54; 2.51). N = 162 (RUs). (B) From left to right: diagnostic performance of the APD/mid-parenchymal ratio to detect TTT >3 min, cutoff 1.38; APD/mid-parenchymal ratio to detect obstructive curve (B, D types of o'Reilly's classification), cutoff 0.88; and APD/mid-parenchymal thickness to detect DFR < 40%, cutoff 3.85. N = 80 (RUs).

Figure 2

Kaplan–Meier curve for the time until operation. Red curve represents time when the model predicted the operation. Follow-up in the horizontal axis in months; p = 0.00004 (logRank). N = 81.

Figure 3

Left ROC curve for the cumulative APD/mid-parenchymal ratio alone (green) in comparison to the β2-M/creatinine ratio with a cumulative APD/mid-parenchymal ratio altogether in the logistic regression model (black) for the detection of TTT > 3 min of at least one RU, p = 0.036, cutoff value 0.03 of the β2-M creatinine ratio, and 2.28 of the cumulative APD/mid-parenchymal ratio. Right ROC curve for the cumulative APD/mid-parenchymal ratio (green) in comparison to β2-M, uNGAL, uAlb, and cumulative APD/mid-parenchymal ratio altogether in the logistic regression model (black) with bigger AUC of DRF < 40% of at least one RU, p = 0.04; cutoff values of the cumulative APD/mid-parenchymal ratio 3.81, β2-M 0.04 mg/l, NGAL 0.35 ng/ml, and uAlb 4.3 mg/l. N = 40.