Utility of Urinary Biomarkers Neutrophil Gelatinase-Associated Lipocalin and Kidney Injury Molecule-1 as a Marker for Diagnosing the Presence of Renal Scar in Children with Vesicoureteral Reflux (VUR)

Abstract

Aim: To explore the possibility of using urinary biomarkers neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) to assess the presence of renal scars in children with Vesicoureteric Reflux (VUR). Materials and Methods: This cross-sectional study was conducted in 94 children aged 0–16 years diagnosed with VUR in the Department of Pediatric Surgery, JIPMER. Urinary biomarkers were measured using the enzyme-linked immunosorbent assay kits, normalized with urinary creatinine (Cr) and compared with severity of VUR (low grade [I and II] and high grade [III, IV, and V]), presence or absence of renal scar in VUR patients and severity of renal scar. Independent Student's t -test, Mann–Whitney U-test, and analysis of variance Kruskal–Wallis test were used for comparison, and receiver operating characteristic (ROC) curve analysis for predicting the accuracy of biomarkers in detecting the presence of renal scars. Results: The median urinary NGAL (uNGAL) value was higher in children with renal scar (1.49 ng/mL) than those without renal scar (0.58 ng/mL) and was statistically significant (<0.001). Whereas median uNGAL/Cr was higher in children with renal scar (0.07) than those without renal scar (0.03) but was not statistically significant ( P = 0.06). Urinary KIM-1 and urinary KIM-1/urinary Cr (uKIM-1/Cr) was not found to be a significant predictor of renal scar. The difference of uNGAL/Cr was comparable between the grades of renal scar but was not statistically significant. On ROC curve analysis, uNGAL had area under the ROC curve (AUC) of 0.769 with 71% of both specificity and sensitivity, whereas uNGAL/Cr was found to be a poor predictor of renal scar with AUC of 0.611, 60% sensitivity, and 61.2% specificity. Conclusion: uNGAL can serve as a noninvasive marker for diagnosing the presence of renal scar in children with VUR and a multicentric more extensive cohort study may be needed to strengthen or negate its role.

The Role of Urinary NGAL in the Management of Primary Vesicoureteral Reflux in Children

“…Thus, contrary to the results reported by Amiri [2] and Eskandarifar [20], in the studies by Ichino [18], Nickawar [19], and Parmaksız [21], the uNGAL levels did not appear to reflect the severity of VUR. Parmaksız's results [1] were consistent with Naik's conclusions: the uNGAL values were higher in children with renal scars than in those without renal scars [22]. Unlike uNGAL, uKIM-1 and uKIM-1/Cr were not able to predict renal scar formation.…”

“…Four original studies aimed specifically to assess the predictive value of uNGAL for the development of RN after they had already demonstrated the significant relationship between increased uNGAL and VUR [4,[21][22][23]. Apart from this, the correlation with the severity of VUR as well as a comparison with other biomarkers such as kidney injury molecule-1 (KIM 1) and liver-type fatty-acid-binding protein (L-FABP) was also sought.…”

The Utility of Noninvasive Urinary Biomarkers for the Evaluation of Vesicoureteral Reflux in Children

“…They also found that urinary NGAL concentrations were significantly higher in patients with VUR than in controls [20]. In their studies, Naik et al and Ganapathy et al also support the value of urinary NGAL in the diagnosis of RS [18,37].…”

“…Regarding RS detection, the studies suggest that higher concentrations of urinary NGAL were found in patients with VUR and RS compared with those with VUR without RS. Thus, NGAL may be a predictive biomarker for RN and its progression to ESKD [18][19][20][21].…”

Exploring the Utility of Urinary Creatinine Adjustment for KIM-1, NGAL, and Cystatin C for the Assessment of Kidney Function: Insights from the C-KidnEES Cohort

“…Significantly elevated creatinine-normalized urinary NGAL [26,27] and KIM-1 [28] and absolute urinary Cys-C [29] levels have been observed in UVR patients with renal scars compared to UVR patients with no renal scars. On the contrary, a few studies have reported no significant increases in creatinine-adjusted or absolute urinary KIM-1, NGAL [30], and Cys-C [31] in subjects with renal scars compared to those with no renal scars. In addition, significantly increased creatinine-normalized urinary NGAL, Cys-C [32], and KIM-1 [33] levels have been identified in subjects with urolithiasis, suggesting a potential role of these biomarkers in predicting associated renal injury.…”