scholarly journals Neutrophil Gelatinase-Associated Lipocalin and Retinol-Binding Protein-4 as Biomarkers for Diabetic Kidney Disease

2020 ◽  
Vol 45 (2) ◽  
pp. 222-232 ◽  
Author(s):  
Fatemeh Abbasi ◽  
Fatemeh Moosaie ◽  
Pegah Khaloo ◽  
Fatemeh Dehghani Firouzabadi ◽  
Seyede Marzie Fatemi Abhari ◽  
...  

Aims: This study was designed to evaluate the conflicting association between 2 tubular protein markers including neutrophil gelatinase-associated lipocalin (NGAL) and retinol-binding protein-4 (RBP-4) with albuminuria and glomerular filtration rate (GFR) and calculate the accuracy of the role of NGAL and RBP-4 in diagnosis of diabetic nephropathy (DN) in patients with type2 diabetes. Methods: This is a cross-sectional study that included 133 patients with type 2 diabetes. There were 3 diabetic study groups with normoalbuminuria, moderately increased albuminuria, severely increased albuminuria, and non-diabetic control group without any renal disease. We analyzed the difference of urinary NGAL (uNGAL) and RBP-4 between nondiabetics and diabetics, as well as within the diabetic group. We also assessed the association between albuminuria and NGAL and RBP-4. Results: The urinary levels of NGAL and RBP-4 were higher in patients with type 2 diabetes compared to nondiabetics as well as in albuminuric diabetics compared to nonalbuminuric patients with diabetes (p value <0.001). These 2 proteins were higher in patients with severely increased albuminuria compared to patients with moderately increased albuminuria, even after adjustment for other metabolic factors (all p < 0.01). Moreover, areas under the curve of NGAL and RBP-4 for the diagnosis of chronic kidney disease were 80.6 and 74.6%, respectively. Conclusion: uNGAL and RBP-4 are potential markers of tubular damage that may increase before the onset of glomerular markers such as albuminuria and GFR in patients with type 2 diabetes. Therefore, these markers can be used as complementary measurements to albuminuria and GFR in the earlier diagnosis of DN.

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Agnieszka Gala-Błądzińska ◽  
Paulina Dumnicka ◽  
Beata Kuśnierz-Cabala ◽  
Katarzyna Rybak ◽  
Ryszard Drożdż ◽  
...  

Background. Two clinical phenotypes of diabetic kidney disease (DKD) have been reported, that is, with or without increased albuminuria. The aim of study was to assess the usefulness of urinary neutrophil gelatinase-associated lipocalin (uNGAL) for the early diagnosis of DKD in the type 2 diabetes mellitus (T2DM). Methods. The study group consisted of 123 patients with T2DM (mean age 62 ± 14 years), with urine albumin/creatinine ratio (uACR) < 300 mg/g and eGFR ≥ 60 ml/min/1.73 m2. The control group included 22 nondiabetic patients with comparable age, sex, and comorbidities. uNGAL, albumin, and creatinine were measured in the first morning urine samples. uACR and uNGAL/creatinine ratios (uNCR) were calculated. Results. In the control group, maximum uNCR was 39.64 µg/g. In T2DM group, 24 patients (20%) had higher results, with the maximum value of 378.6 µg/g. Among patients with uNCR > 39.64 µg/g, 13 (54%) did not have markedly increased albuminuria. Women with T2DM had higher uNCR than men (p<0.001), without difference in uACR (p=0.09). uNCR in T2DM patients correlated significantly with HbA1c. Sex, total cholesterol, and uACR were independent predictors of uNCR above 39.64 µg/g. Conclusions. Increased uNGAL and uNCR may indicate early tubular damage, associated with dyslipidemia and worse diabetes control, especially in females with T2DM.


2016 ◽  
Vol 11 ◽  
pp. BMI.S33191 ◽  
Author(s):  
Mohamed H. Mahfouz ◽  
Adel M. Assiri ◽  
Mohammed H. Mukhtar

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.


2013 ◽  
Vol 16 (2) ◽  
pp. 388-397 ◽  
Author(s):  
Vivian C. Luft ◽  
Mark Pereira ◽  
James S. Pankow ◽  
Christie Ballantyne ◽  
David Couper ◽  
...  

Background: Retinol binding protein 4 (RBP4) has been described as a link between impaired glucose uptake in adipocytes and systemic insulin sensitivity. Objective: To determine whether RBP4 fasting levels predict the development of type 2 diabetes. Methods: Using a case-cohort design, we followed 543 middle-aged individuals who developed diabetes and 537 who did not over ~9 years within the population-based Atherosclerosis Risk in Communities Study. Weighted Cox proportional hazards analyses permitted statistical inference of the RBP4 – incident diabetes associations to the entire cohort. Results: Women in the highest tertile of RBP4 presented greater risk of developing diabetes (HR = 1.74; 95%CI 1.03 – 2.94) in analyses adjusted for age, ethnicity, study center, parental history of diabetes, hypertension, glomerular filtration rate, body mass index, waist-hip ratio, nonesterified fatty acids, adiponectin, leptin, triglycerides and HDL-C. When additionally adjusted for fasting insulin, this association’s significance became borderline (HR = 1.68; 95%CI 1.00 – 2.82). No association between RBP4 levels and incident diabetes was found in men. Conclusion: These findings suggest that RBP4 levels may be directly involved in the pathogenesis of type 2 diabetes in women.


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