263 URINARY NEUTROPHIL GELATINASE-ASSOCIATED LIPOCALIN (NGAL) IS A POTENTIAL NON-INVASIVE MARKER FOR RENAL SCARRING IN PATIENTS WITH VESICOURETERAL REFLUX

Abstract

You have accessJournal of UrologyPediatrics: Basic Research1 Apr 2011263 URINARY NEUTROPHIL GELATINASE-ASSOCIATED LIPOCALIN (NGAL) IS A POTENTIAL NON-INVASIVE MARKER FOR RENAL SCARRING IN PATIENTS WITH VESICOURETERAL REFLUX Manabu Ichino, Mamoru Kusaka, Hitomi Sasaki, Takahiro Maruyama, Kiyohito Ishikawa, Ryoichi Shiroki, and Kiyotaka Hoshinaga Manabu IchinoManabu Ichino Toyoake Aichi, Japan More articles by this author , Mamoru KusakaMamoru Kusaka Toyoake Aichi, Japan More articles by this author , Hitomi SasakiHitomi Sasaki Toyoake Aichi, Japan More articles by this author , Takahiro MaruyamaTakahiro Maruyama Toyoake Aichi, Japan More articles by this author , Kiyohito IshikawaKiyohito Ishikawa Toyoake Aichi, Japan More articles by this author , Ryoichi ShirokiRyoichi Shiroki Toyoake Aichi, Japan More articles by this author , and Kiyotaka HoshinagaKiyotaka Hoshinaga Toyoake Aichi, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.354AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Renal scarring is a serious complication that often occurs after chronic pyelonephritis in the presence of vesicoureteral reflux (VUR). In our recent study, we established a rat model of renal scar formation after bacterial infection. Using this model system, we performed global analysis of gene expression by microarray and identified NGAL as one of the most up-regulated genes following renal injury. The high levels of NGAL expression were subsequently confirmed at both the RNA and protein levels. In our present study, we investigated the urinary NGAL levels in patients with childhood VUR and evaluated its potential usefulness as a biomarker of renal scarring. METHODS A total of 34 patients diagnosed with VUR without the evidence of current urinary tract infection and 28 normal healthy children were enrolled in this study. Renal scars were evaluated by a 99mTc-DMSA renal scan in 24 of the VUR cases. Urinary NGAL levels were monitored by Enzyme-Linked ImmunoSorbent Assay (ELISA). RESULTS In our initial analyses, the NGAL levels were measured in urine samples from normal healthy children. These levels were found to be much higher in infant donors of less than 1 year of age than the reported normal levels (0.7–9.8 ng/ml). Even after the values were normalized with the urinary concentration of creatinine, the ratios were still high in samples from infants. We next evaluated the urinary NGAL concentration in 34 VUR cases and compared these levels with those of normal controls. We further normalized the NGAL/creatinine values to the age-specific average. The urinary NGAL levels were found to be significantly high in the VUR group (p < 0.01). We further compared the urinary NGAL levels in patients with and without renal scarring as demonstrated by a 99mTc-DMSA renal scan. The presence of renal scarring was observed to be significantly associated with high NGAL values (p < 0.005). We applied a cut-off value of 1 and this allowed for both high sensitivity (89.5%) and high specificity (100%) and suggested that high urinary NGAL values are diagnostic for the presence of renal scarring (AUC of ROC curve, 0.947). Assays for serum creatinine, urinary BMG and NAG are routine tests for evaluating renal function but do not predict the presence of renal scarring. CONCLUSIONS Urinary NGAL levels are significantly higher than normal in VUR patients with renal scarring without the evidence of UTI. The estimation of urinary NGAL may thus be useful as a non-invasive diagnostic or prognostic biomarker of renal scarring. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e106 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Manabu Ichino Toyoake Aichi, Japan More articles by this author Mamoru Kusaka Toyoake Aichi, Japan More articles by this author Hitomi Sasaki Toyoake Aichi, Japan More articles by this author Takahiro Maruyama Toyoake Aichi, Japan More articles by this author Kiyohito Ishikawa Toyoake Aichi, Japan More articles by this author Ryoichi Shiroki Toyoake Aichi, Japan More articles by this author Kiyotaka Hoshinaga Toyoake Aichi, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...