Isoforms of Retinol binding protein 4 (RBP4) are increased in chronic diseases of the kidney but not of the liver

Simone K Frey,Martin O Weickert,Beate Schlosser,Jens Raila,Florian J Schweigert,Andreas Fh Pfeiffer,Andrea Henze,Thomas Berg,Britta Nagl,Walter Zidek,Martin Tepel

doi:10.1186/1476-511x-7-29

Abstract

BackgroundThe levels of retinol-binding protein 4 (RBP4) – the carrier protein for Vitamin A in plasma – are tightly regulated under healthy circumstances. The kidney, the main site of RBP4 catabolism, contributes to an elevation of RBP4 levels during chronic kidney disease (CKD) whereas during chronic liver disease (CLD) RBP4 levels decrease. Little is known about RBP4 isoforms including apo-RBP4, holo-RBP4 as well as RBP4 truncated at the C-terminus (RBP4-L and RBP4-LL) except that RBP4 isoforms have been reported to be increased in hemodialysis patients. Since it is not known whether CLD influence RBP4 isoforms, we investigated RBP4 levels, apo- and holo-RBP4 as well as RBP4-L and RBP4-LL in plasma of 36 patients suffering from CKD, in 55 CLD patients and in 50 control subjects. RBP4 was determined by ELISA and apo- and holo-RBP4 by native polyacrylamide gel electrophoresis (PAGE). RBP4-L and RBP4-LL were analyzed after immunoprecipitation by mass spectrometry (MALDI-TOF-MS).ResultsRBP4 isoforms and levels were highly increased in CKD patients compared to controls (P < 0.05) whereas in CLD patients RBP4 isoforms were not different from controls. In addition, in hepatic dysfunction RBP4 levels were decreased whereas the amount of isoforms was not affected.ConclusionThe occurrence of RBP4 isoforms is not influenced by liver function but seems to be strongly related to kidney function and may therefore be important in investigating kidney function and related disorders.

Highlights

The levels of retinol-binding protein 4 (RBP4) – the carrier protein for Vitamin A in plasma – are tightly regulated under healthy circumstances
Serum C-reactive protein (CRP) levels were higher in chronic liver disease (CLD) and chronic kidney disease (CKD) patients compared to controls (P < 0.001, both), and CRP was elevated in CKD patients compared to CLD (P < 0.001)
Our results show that RBP4 levels were significantly elevated in serum of CKD patients compared to both, CLD patients and controls

Summary

Introduction

The levels of retinol-binding protein 4 (RBP4) – the carrier protein for Vitamin A in plasma – are tightly regulated under healthy circumstances. Little is known about RBP4 isoforms including apo-RBP4, holo-RBP4 as well as RBP4 truncated at the C-terminus (RBP4-L and RBP4-LL) except that RBP4 isoforms have been reported to be increased in hemodialysis patients. RBP4 levels have been reported to be elevated in insulin resistant subjects as well as in subjects with obesity and type 2 diabetes (T2DM) [4] These diseases involve liver and kidney disorders in late stages [5,6]. In healthy individuals RBP4 is mainly synthesized in the liver and secreted into the circulation in a 1:1:1 complex with ROH (holo-RBP4) and transthyretin (TTR) [7,8]. Dysfunctions of both, the liver and kidneys, are known to influence RBP4 homeostasis [13,16,17,18]: chronic kidney diseases (CKD) and chronic liver diseases (CLD) interfere with RBP4 metabolism through their action on RBP4 synthesis and catabolism [13,19]

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