RBP4: A Culprit for Insulin Resistance in End Stage Renal Disease That Can Be Cleared by Hemodiafiltration

Fabrizio Grosjean,Antonio Dal Canton,Teresa Rampino,Rosario Maccarrone,Carmelo Libetta,Pasquale Esposito

doi:10.1155/2017/7270595

Abstract

Introduction Retinol Binding Protein 4 (RBP4) is mainly excreted by the kidney and plays a pivotal role in insulin resistance (IR). In our study, we evaluated the association between RBP4 and IR in hemodialysis subjects (HD). We also assessed how circulating RBP4 could be influenced by kidney transplant or different dialytic techniques. Methods RBP4 serum levels were evaluated in HD (n = 16) and matched healthy controls (C; n = 16). RBP4 and glucose transporter type 4 (GLUT4) mRNA expressions were also determined in adipose tissue. Circulating RBP4 was evaluated after kidney transplant (n = 7) and in hemodialysis patients (n = 10) enrolled in a cross-over study treated with standard bicarbonate dialysis (BD) or hemodiafiltration (HDF). Results HOMA index (P < 0.05) and serum RBP4 (P < 0.005) were higher in HD compared to C. RBP4 levels positively correlated with fasting serum glucose (P < 0.05). RBP4 mRNA was lower in HD compared to C (P < 0.05) and positively correlated with kidney function (P < 0.05) and GLUT4 mRNA (P < 0.001). Transplant or HDF reduced circulating RBP4 (P < 0.01 and P < 0.05, resp.). Our results demonstrate that IR is associated with high circulating RBP4 and that suppressed RBP4 adipose tissue expression is accompanied by reduced GLUT4 expression in HD. Renal transplantation or HDF are effective in lowering serum RBP4 levels.

Highlights

Retinol Binding Protein 4 (RBP4) is mainly excreted by the kidney and plays a pivotal role in insulin resistance (IR)
IR is defined by normal fasting serum glucose associated with high serum insulin levels, a state that results in type 2 diabetes when the increased insulin secretion is no longer able to compensate for impaired peripheral insulin responsiveness [2]
Our study shows that serum RBP4 levels are four times higher in End Stage Renal Disease (ESRD) patients on maintenance hemodialysis compared to subjects with normal renal function

Summary

Introduction

Retinol Binding Protein 4 (RBP4) is mainly excreted by the kidney and plays a pivotal role in insulin resistance (IR). Circulating RBP4 was evaluated after kidney transplant (n = 7) and in hemodialysis patients (n = 10) enrolled in a cross-over study treated with standard bicarbonate dialysis (BD) or hemodiafiltration (HDF). RBP4 levels positively correlated with fasting serum glucose (P < 0.05). Our results demonstrate that IR is associated with high circulating RBP4 and that suppressed RBP4 adipose tissue expression is accompanied by reduced GLUT4 expression in HD. Renal transplantation or HDF are effective in lowering serum RBP4 levels. IR is defined by normal fasting serum glucose associated with high serum insulin levels, a state that results in type 2 diabetes when the increased insulin secretion is no longer able to compensate for impaired peripheral insulin responsiveness [2].

Methods

Results

Conclusion