The Role of Circulating RBP4 in the Type 2 Diabetes Patients with Kidney Diseases: A Systematic Review and Meta-Analysis

Abstract

Background. Diabetic nephropathy is a common and serious complication of diabetes mellitus (DM) and is one of the leading causes of end-stage renal disease worldwide. Although there have been many investigations on biomarkers for DN, there is no consistent conclusion about reliable biomarkers. The purpose of this study was to perform a systematic review and meta-analysis of the role of circulating retinol-binding protein 4 (RBP4) in the type 2 diabetes mellitus (T2DM) patients with kidney diseases. Materials and Methods. We searched the PubMed, MEDLINE, EMBASE, and Web of Science databases for publications. For the 12 cross-sectional studies that we included in the review, we calculated standard mean differences (SMD) with 95% confidence intervals (CI) for continuous data when the applied scales were different. Risk of bias of included trials was assessed by using the Newcastle-Ottawa Scale. Results. RBP4 concentrations in the micro-, macro-, or micro+macroalbuminuria groups were significantly higher than those in the normal albuminuria group of T2DM patients [P=0.001, SMD 1.07, 95% CI (0.41, 1.73)]. The estimated glomerular filtration rate (eGFR) was negatively associated with circulating RBP4 concentrations in patients with T2DM [summary Fisher’s Z=−0.48, 95% CI (-0.69, -0.26), P<0.0001]. The albumin-to-creatinine ratio (ACR) was positively associated with circulating RBP4 concentrations in patients with T2DM [summary Fisher’s Z=0.20, 95% CI (0.08, 0.32), P=0.001]. Conclusion. The levels of circulating RBP4 were significantly higher both in T2DM subjects with micro/macroalbuminuria and in T2DM subjects with declined eGFR. The levels of circulating RBP4 were positively correlated with ACR but negatively correlated with eGFR. Circulating RBP4 could be a reliable biomarker for kidney diseases in T2DM.

Correlation and Diagnostic Value of Serum Cys-C, RBP4, and NGAL with the Condition of Patients with Traumatic Acute Kidney Injury

“…e concentration of Cys C in the blood is determined only by the glomerular filtration rate and is not affected by physiological and pathological factors such as age and inflammation, so it can be used as a sensitive indicator to assess glomerular and tubular lesions [14,15]. As an indicator that can also reflect the function of glomeruli and tubules, RBP4 is getting more and more attention in clinical practice, and it was mainly used as a screening marker for diabetic nephropathy and attracted attention in the early stage [16]. RBP4 is mainly synthesized by hepatocytes and is produced at a constant rate, and most of it can be reabsorbed by the Evidence-Based Complementary and Alternative Medicine renal tubules after passing through the glomerular filtration membrane, so the concentration of RBP4 in the blood is less affected by other factors when it is under normal physiological conditions [17].…”

Effect of Add-On Therapy of Sodium-Glucose Cotransporter 2 Inhibitors and Dipeptidyl Peptidase 4 Inhibitors on Adipokines in Type 2 Diabetes Mellitus

“…RBP4 is associated with cardiovascular risk in type 2 diabetic subjects with varying clinical presentations [32]. Recent studies demonstrated that RBP4 levels significantly alter with variables related to insulin resistance, obesity, type 2 diabetes and metabolic syndrome [32][33][34]. Furthermore, there is some indication that reduced RBP4 levels decrease the risk of diabetic nephropathy [34].…”

“…Recent studies demonstrated that RBP4 levels significantly alter with variables related to insulin resistance, obesity, type 2 diabetes and metabolic syndrome [32][33][34]. Furthermore, there is some indication that reduced RBP4 levels decrease the risk of diabetic nephropathy [34]. The plasma level of RBP4 is higher in type 2 diabetic patients when compared with normal controls [35].…”

Analysis of key genes and pathways associated with the pathogenesis of Type 2 diabetes mellitus

“…Metabolism of proteins [38], metabolism [39], the citric acid (TCA) cycle and respiratory electron transport [40], gluconeogenesis [41], immune system [42], heterocyclic compound binding [43], protein binding [44], establishment of localization [45], cellular metabolic process [46], cytoplasm [47] and catalytic activity [48] were the GO terms and signaling pathways responsible for the advancement of T2DM. A previous study showed that IGFBP2 [88], CPT1A [89], ALDH1B1 [90], ESRRA (estrogen related receptor alpha) [91], NISCH (nischarin) [92], SSTR3 [93], ND1 [94], NCOR2 [95], RBP4 [96], GSTP1 [97], CYB5A [98], G6PC2 [99], DNAJC15 [100], TMED6 [101], PSMD6 [102], CLU (clusterin) [103], TTR (transthyretin) [104], TXN (thioredoxin) [105], LAMTOR1 [106], GLUL (glutamate-ammonia ligase) [107], NEU1 [108], HSPA8 [109], AP3S2 [110], COX4I1 [111], MT2A [112] MTCH2 [113], ESD (esterase D) [114], UBE2L6 [115], SCD (stearoyl-CoA desaturase) [116], MGST3 [117] [187], GRB2 [188], ZMPSTE24 [189], COX6B1 [190], SQSTM1…”