Retinol-binding protein 4 versus albuminuria as predictors of estimated glomerular filtration rate decline in patients with type 2 diabetes

Background: Since the increase in some tubular damage biomarkers can be observed at the early stage of diabetic nephropathy, even in the absence of albuminuria, we aimed to investigate if urinary albumin is superior than tubular damage marker, such as serum retinol-binding protein 4 (RBP4), in predicting renal function decline (defined as estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2) in the cohort of patients with type 2 diabetes mellitus (T2D). Materials and Methods: A total of 106 sedentary T2D patients (mean [± standard deviation] age 64.9 [±6.6] years) were included in this cross-sectional study. Anthropometric and biochemical parameters (fasting glucose, glycated hemoglobin [HbA1c], lipid parameters, creatinine, RBP4, high sensitivity C-reactive protein [hsCRP], urinary albumin excretion [UAE]), as well as blood pressure were obtained. Results: HsCRP (odds ratio [OR] =0.754, 95% confidence interval [CI] (0.603–0.942), P = 0.013) and RBP4 (OR = 0.873, 95% CI [0.824–0.926], P < 0.001) were independent predictors of eGFR decline. Moreover, although RBP4 and UAE as single diagnostic parameters of renal impairment showed excellent clinical accuracy (area under the curve [AUC] = 0.900 and AUC = 0.940, respectively), the Model which included body mass index, HbA1c, triglycerides, hsCRP, and RBP4 showed statistically same accuracy as UAE, when UAE was used as a single parameter (AUC = 0.932 vs. AUC = 0.940, respectively; P for AUC difference = 0.759). As well, the Model had higher sensitivity and specificity (92% and 90%, respectively) than single predictors, RBP4, and UAE. Conclusion: Although serum RBP4 showed excellent clinical accuracy, just like UAE, a combination of markers of tubular damage, inflammation, and traditional markers has the higher sensitivity and specificity than UAE alone for prediction renal impairment in patients with T2D.

[1]  G. Kocic,et al.  Xanthine oxidase and uric acid as independent predictors of albuminuria in patients with diabetes mellitus type 2 , 2018, Clinical and Experimental Medicine.

[2]  A. Ninić,et al.  Are visceral adiposity index and lipid accumulation product reliable indices for metabolic disturbances in patients with type 2 diabetes mellitus? , 2018, Journal of clinical laboratory analysis.

[3]  B. Kestenbaum,et al.  Kidney function is associated with an altered protein composition of high-density lipoprotein. , 2017, Kidney international.

[4]  A. Ninić,et al.  Association between unfavorable lipid profile and glycemic control in patients with type 2 diabetes mellitus , 2017, Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences.

[5]  G. Kocic,et al.  Relationship between Oxidative Stress, Inflammation and Dyslipidemia with Fatty Liver Index in Patients with Type 2 Diabetes Mellitus , 2017, Experimental and Clinical Endocrinology & Diabetes.

[6]  I. Soldatovic,et al.  Bioavailable testosterone is independently associated with Fatty Liver Index in postmenopausal women , 2017, Archives of medical science : AMS.

[7]  H. Deng,et al.  RBP4/Lp-PLA2/Netrin-1 signaling regulation of cognitive dysfunction in diabetic nephropathy complicated with silent cerebral infarction. , 2017, Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association.

[8]  P. Lotufo,et al.  Serum RBP4 and CKD: Association with insulin resistance and lipids. , 2017, Journal of diabetes and its complications.

[9]  K. Al-Rubeaan,et al.  Assessment of the diagnostic value of different biomarkers in relation to various stages of diabetic nephropathy in type 2 diabetic patients , 2017, Scientific Reports.

[10]  B. Bjelakovic,et al.  The Association Between Retinol-Binding Protein 4 and Cardiovascular Risk Score is Mediated by Waist Circumference in Overweight/Obese Adolescent Girls , 2017, Acta clinica Croatica.

[11]  M. Saif-Elnasr,et al.  Role of Vitamin D on glycemic control and oxidative stress in type 2 diabetes mellitus , 2017, Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences.

[12]  A. Feizi,et al.  Association of retinol-binding protein 4 with metabolic syndrome in first-degree relatives of type 2 diabetic patients , 2017, Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences.

[13]  J. Chudek,et al.  Increased plasma RBP4 concentration in older hypertensives is related to the decreased kidney function and the number of antihypertensive drugs-results from the PolSenior substudy. , 2017, Journal of the American Society of Hypertension : JASH.

[14]  Wael A Alanazi,et al.  Diabetes-Induced Reactive Oxygen Species: Mechanism of Their Generation and Role in Renal Injury , 2017, Journal of diabetes research.

[15]  J. Kotur-Stevuljević,et al.  Relationship between Cystatin C, Retinol-binding Protein 4 and Framingham Risk Score in Healthy Postmenopausal Women. , 2016, Archives of Iranian medicine.

[16]  R. Glassock Control of albuminuria in overt diabetic nephropathy: durability counts. , 2016, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[17]  A. Miranda-Díaz,et al.  Oxidative Stress in Diabetic Nephropathy with Early Chronic Kidney Disease , 2016, Journal of diabetes research.

[18]  Zemenu Tamir,et al.  Urinary Markers of Tubular Injury in Early Diabetic Nephropathy , 2016, International journal of nephrology.

[19]  M. Varma,et al.  Serum Total Sialic Acid and Highly Sensitive C-reactive Protein: Prognostic Markers for the Diabetic Nephropathy , 2016, Journal of laboratory physicians.

[20]  A. Assiri,et al.  Assessment of Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Retinol-Binding Protein 4 (RBP4) in Type 2 Diabetic Patients with Nephropathy , 2016, Biomarker insights.

[21]  Q. Liu,et al.  The association between high-sensitivity C-reactive protein concentration and diabetic nephropathy: a meta-analysis. , 2015, European review for medical and pharmacological sciences.

[22]  H. Nasri,et al.  Diabetes mellitus and renal failure: Prevention and management , 2015, Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences.

[23]  G. Papaetis,et al.  Central obesity, type 2 diabetes and insulin: exploring a pathway full of thorns , 2015, Archives of medical science : AMS.

[24]  M. Abdi,et al.  Diagnostic value of cystatin C for diagnosis of early renal damages in type 2 diabetic mellitus patients: The first experience in Iran , 2015, Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences.

[25]  E. Porrini,et al.  Non-proteinuric pathways in loss of renal function in patients with type 2 diabetes. , 2015, The lancet. Diabetes & endocrinology.

[26]  L. Nyström,et al.  The risk for diabetic nephropathy is low in young adults in a 17‐year follow‐up from the Diabetes Incidence Study in Sweden (DISS). Older age and higher BMI at diabetes onset can be important risk factors , 2015, Diabetes/metabolism research and reviews.

[27]  Z. Q. Zhang,et al.  Decreased retinol-binding protein 4 in the sera of patients with end-stage renal disease after kidney transplantation. , 2014, Genetics and molecular research : GMR.

[28]  K. Al-Rubeaan,et al.  Diabetic Nephropathy and Its Risk Factors in a Society with a Type 2 Diabetes Epidemic: A Saudi National Diabetes Registry-Based Study , 2014, PloS one.

[29]  J A Swets,et al.  Measuring the accuracy of diagnostic systems. , 1988, Science.