Urinary Retinol Binding Protein (RBP) Level as an early Biomarker of Diabetic Nephropathy in type 2 Diabetic Patients

Serum fatty acid-binding protein 4 (FABP4) has been linked to renal dysfunction. This study evaluated the association between serum FABP4 and the radioisotope glomerular filtration rate (rGFR) in type 2 diabetic patients (T2DM) with early diabetic nephropathy. Twenty healthy controls and 172 patients with T2DM were enrolled. Serum FABP4 and renal impairment biomarkers including urinary albumin-to-creatinine ratio (UACR), serum retinal-binding protein 4 (RBP4), urinary cystatin C-to-creatinine ratio (CysC/Cr), and neutrophil gelatinase-associated lipocalin-to-creatinine ratio (NGAL/Cr) were measured. Diethylenetriaminepentaacetic acid (99mTc-DTPA) was used to test rGFR. Serum FABP4 levels were higher in T2DM patients compared with the controls. There was no significant correlation between serum FABP4 and UACR in patients with T2DM. Multivariate stepwise regression analysis showed that, in patients with T2DM, FABP4 was significantly associated with rGFR while CysC/Cr and RBP4 were significantly associated with UACR independently. But UACR had no independent association with rGFR. NGAL/Cr had no significant correlation with either rGFR or UACR. FABP4 might be an early biomarker for diabetic nephropathy if combined with UACR.

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Assessment of Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Retinol-Binding Protein 4 (RBP4) in Type 2 Diabetic Patients with Nephropathy

Biomarker Insights ◽

10.4137/bmi.s33191 ◽

2016 ◽

Vol 11 ◽

pp. BMI.S33191 ◽

Cited By ~ 22

Author(s):

Mohamed H. Mahfouz ◽

Adel M. Assiri ◽

Mohammed H. Mukhtar

Keyword(s):

Early Detection ◽

Binding Protein ◽

Retinol Binding Protein ◽

Diabetic Patients ◽

Type 2 Diabetic Patients ◽

Retinol Binding Protein 4 ◽

Neutrophil Gelatinase Associated Lipocalin ◽

Neutrophil Gelatinase ◽

Type 2 Diabetic

Diabetic nephropathy (DN) is one of the most serious microvascular complications of diabetes. The study aims to evaluate the diagnostic value of serum neutrophil gelatinase-associated lipocalin (NGAL) and retinol-binding protein 4 (RBP4) as biomarkers for early detection of nephropathy in type 2 diabetic patients. The current study was performed on 150 type 2 diabetic patients. These patients were classified into three equal groups according to their albumin/creatinine ratio (ACR), including patients with normoalbuminuria (ACR <30 mg/g creatinine), patients with microalbuminuria (ACR = 30–300 mg/g creatinine), and patients with macroalbuminuria (ACR >300 mg/g creatinine). Fifty apparently healthy subjects matching the same age and socioeconomic status with diabetic subjects were selected as a control group. The plasma glucose, insulin, glycosylated hemoglobin (HbA1c), homeostasis model assessment of insulin resistance (HOMA-IR), lipid profile, urea, creatinine, cystatin C, glomerular filtration rate (GFR), NGAL, and RBP4 were measured in the studied groups. Significantly elevated NGAL and RBP4 levels were observed in micro- and macroalbuminuric diabetic groups when compared to the control and normoalbuminuric diabetic groups. NGAL and RBP4 were found to correlate positively with duration of diabetes, systolic and diastolic blood pressure, glucose, HbA1c, HOMA-IR, triacylglycerol, and ACR, but correlate inversely with GFR in DN groups. Receiver operating characteristic curves revealed that for early detection of DN, the best cutoff values to discriminate DN and diabetic without nephropathy groups were 91.5 ng/mL for NGAL with 87% sensitivity, 74% specificity, and area under the curve (AUC) = 0.881; 24.5 ng/mL for RBP4 with 84% sensitivity, 90% specificity, and AUC = 0.912; and 37.5 mg/g creatinine for ACR with 89% sensitivity, 72% specificity, and AUC = 0.819. RBP4 is more specific (90% specificity) than NGAL (74% specificity) and ACR (72% specificity). Therefore, RBP4 marker may serve as a tool to follow-up clinical monitoring of the development and progression of DN.

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