Clinical Application Of Urinary NGAL In Early Type 2 Diabetic Nephropathy

Background and Aims: Diabetic nephropathy(DN)is the most serious microvascular complications in type 2 diabetes mellitus(T2DM),which will eventually lead to end-stage renal disease.Early diagnosis and treatment can prevent the progression of disease to the irreversible stage.Currently,as the gold standard in clinical diagnosis,microalbuminuria still has some limitations.Therefore,it is necessary to find other sensitive and specific biomarkers that appearance earlier than microalbuminuria.In recent years,a number of studies have shown that tubular markers such as neutrophil gelatinase-associated lipocalin(NGAL)is already elevated even in the early stage of type 2 diabetic nephropathy(T2DN),and is correlated with other markers of renal function.The purpose of this study was to investigate the clinical application value of urinary NGAL levels in the early diagnosis and assessment of T2 DN.Methods: A group of 112 T2 DM patients were recruited.Based on urinary albumin/creatinine ratio(UACR),diabetic patients were divided into three groups: 38 with normoalbuminuria(NA group),36 with microalbuminuria(MA group)and 38 with macroalbuminuria(LA group).In addition,32 healthy subjects served as controls(NC group).First-voided morning urine samples were collected and centrifuged,then stored until analysis.Urinary NGAL was measured by chemiluminescent microparticle immunoassay using Abbott ARCHITECT Urine NGAL Reagent Kit,and urinary NGAL/creatinine ratio was calculated to account for the influence of urinary dilution.Urinary NGAL and urinary NGAL/creatinine ratio were compared and their correlations with other clinical parameters were analyzed among the control group and different diabetic groups.Results: Urinary NGAL in the control group showed no obvious difference compared with the diabetic groups(P>0.05),but urinary NGAL/creatinine ratio in the T2 DM were all markedly increased(P<0.05).In the diabetic groups,urinary NGAL/creatinine ratio in macroalbuminuria group was significantly higher than that in normoalbuminuria group(P < 0.05).However,there was no significant difference between normoalbuminuria and microalbuminuria group(P>0.05),either between microalbuminuria and macroalbuminuria group(P>0.05).Correlation analysis showed that urinary NGAL/creatinine ratio positively correlated with UACR,diabetic duration and glycated hemoglobin(HbA1c)(P<0.05).Receiver operating characteristic(ROC)curve analysis showed that the best cut off value of urinary NGAL/creatinine ratio to detect early T2 DN was 28.04ng/mg,with the area under the curve(AUC)of 0.605,sensitivity of 43.2% and specificity of 78.9%.If we used urinary NGAL/creatinine ratio with diabetic duration and HbA1 c to detect early T2 DN,the ROC curve showed that the best sensitivity and specificity was 67.6%,76.3%.Conclusions: Urinary NGAL levels was significantly elevated in T2 DM patients with normoalbuminuria,so it may be a earlier marker than microalbuminuria to diagnose T2 DN.Furthermore,urinary NGAL levels can evaluate the severity of the disease to a certain extent.