Urinary Biomarkers NGAL and Beta-2 Microglobulin for Detection of Diabetic Nephropathy in Type 1 Diabetes Mellitus

Abstract

Abstract Objectives: Urinary neutrophil gelatinase-associated lipocalin (NGAL) and beta-2 microglobulin(β2M) have been evaluated as markers of tubular damage in type 2 diabetes mellitus. There is limited data on their performance to screen nephropathy in type 1 diabetes mellitus (T1DM). Methods: This case-control study enrolled 40 children with T1DM and 40 age-matched controls age 2-18 years. Subjects with coexisting renal disorder and syndromic diabetes mellitus were excluded. Fasting plasma glucose, glycated hemoglobin (HbA1c), and renal function were measured. Urinary levels of urine albumin-creatinine ratio (ACR), neutrophil gelatinase-associated lipocalin (NGAL) and beta-2 microglobulin (β2M) were measured for an associated with disease duration, glycemic control and microalbuminuria. Correlation (r) was measured for statistical association between biochemical markers and area-under-curve (AUC) calculated to predict nephropathy. Results: The median (IQR) age of cases and controls was 10.6(8,14.2) and 10.7 (8.4,13.7) years, respectively, disease duration 4 (3,6.8) years and HbA1c 10.9(9.,13.1)% in cases. Microalbuminuria was seen in 14(35%) but none had macroalbuminuria.The urinary ACR and NGAL were significantly higher in cases than controls [19.38 (10.27,35.26) and 6.49 (3.10,11.65) µg/mg; p<0.001] and [352.21(191.49,572.45) and 190.54 (125.91,322.83) ng/mg; p=0.006], respectively, unlike β2M [1.7 (0.43,6.02) and 2.12 (1.05,4.47) µg/mg; p=0.637]. Children with higher HbA1C (>10%) had higher urinary ACR, NGAL and β2M levels than those with HbA1C<10%. Urinary ACR showed positive correlation with NGAL/creatinine (r= 0.38, p value=0.019) and β2M/ creatinine (r=0.48, p value= 0.004) in cases. The AUC was 0.57 (95% CI 0.36,0.78); p value= 0.48 for NGAL/creatinine, and 0.62 (95%CI 0.43,0.81); p value=0.21 for β2M /creatinine to predict microalbuminuria (ACR >30mg/g). Conclusion: Urinary biomarkers NGAL and β2M showed a good correlation with ACR suggesting their role in screening of diabetic tubulopathy before overt glomerular damage in T1DM.