Abstract
It has been reported that retinol-binding protein 4 (RBP4) is associated to adiposity, insulin resistance, and type 2 diabetes. Meanwhile, circulating RBP4 levels are also affected by renal function. The aim of the present study is to investigate whether serum levels of RBP4 are primarily associated with different stages of chronic kidney disease (CKD) or type 2 diabetes, if there is more potential relevance between RBP4 and renal replacement therapy. The serum levels of RBP4 were assessed by commercial competitive enzyme-linked immunosorbent assay (ELISA) kit in 212 patients with the CKD stages 1—5 and in 24 healthy controls, while its correlation with clinical and metabolic parameters was analyzed. The serum level of RBP4 had a strong correlation with estimated glomerular filtration rate (eGFR) (P < 0.001). Stratified by eGFR and treatment, no more differences in RBP4 serum concentration were detected between type 2 diabetic and non-diabetic subjects [CKD stages 1—5, non-dialysis (ND), hemodialysis (HD) and peritoneal dialysis (PD); P >0.05 for all]. The elevation of RBP4 become higher in HD than in PD and ND in CKD5 patients (P = 0.008 and P = 0.04, respectively), while there was no significant difference between PD and ND groups. Multivariate linear regression analysis demonstrated three independent predictors of eGFR (β = −0.676, P < 0.001), C-reactive protein (CRP) (β = −0.573, P < 0.001) and creatine (β = 0.509, P = 0.024) in the study population. The study results demonstrated that the serum level of RBP4 was negatively related to the eGFR, whether diabetes mellitus (DM) affected the blood concentration of RBP4 or not. And the serum level of RBP4 exhibited significant difference in different renal replacement therapies.
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HENZE A, FREY S K, RAILA J, et al. Evidence that kidney function but not type 2 diabetes determines retinol-binding protein 4 serum levels [J]. Diabetes, 2008, 57(12): 3323–3326.
ZIEGELMEIER M, BACHMANN A, SEEGER J, et al. Serum levels of adipokine retinol-binding protein-4 in relation to renal function [J]. Diabetes Care, 2007, 30(10): 2588–2592.
RAILA J, HENZE A, SPRANGER J, et al. Microalbuminuria is a major determinant of elevated plasma retinol-binding protein 4 in type 2 diabetic patients [J]. Kidney International, 2007, 72(4): 505–511.
YANG Q, GRAHAM TE, MODY N, et al. Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes [J]. Nature, 2005, 436(7049): 356–362.
GRAHAM T E, YANG Q, BLüHER M, et al. Retinolbinding protein 4 and insulin resistance in lean, obese, and diabetic subjects [J]. The New England Journal of Medicine, 2006, 354(24): 2552–2563.
RAILA J, WILLNOW T E, SCHWEIGERT F J. Megalin-mediated reuptake of retinol in the kidneys of mice is essential for vitamin A homeostasis [J]. The Journal of Nutrition, 2005, 135(11): 2512–2516.
BLOMHOFF R. Transport and metabolism of vitamin A [J]. Nutrition Reviews, 1994, 52(2): 13–23.
NAYLOR H M, NEWCOMER M E. The structure of human retinol-binding protein (RBP) with its carrier protein transthyretin reveals an interaction with the carboxy terminus of RBP [J]. Biochemistry, 1999, 38(9): 2647–2653.
WIHLER C, SCHäFER S, SCHMID K, et al. Renal accumulation and clearance of advanced glycation endproducts in type 2 diabetic nephropathy: Effect of angiotensin-converting enzyme and vasopeptidase inhibition [J]. Diabetologia, 2005, 48(8): 1645–1653.
KIERNAN U A, TUBBS K A, NEDELKOV D, et al. Comparative phenotypic analyses of human plasma and urinary retinol binding protein using mass spectrometric immunoassay [J]. Biochemical and Biophysical Research Communications, 2002, 297(2): 401–405.
JACONI S, SAURAT J H, SIEGENTHALER G. Analysis of normal and truncated holo-and apo-retinolbinding protein (RBP) in human serum: Altered ratios in chronic renal failure [J]. European Journal of Endocrinology, 1996, 134(5): 576–582.
WANG F, YIN J Y, LU Z Y, et al. Limb ischemic preconditioning protects against contrastinduced nephropathy via renalase [J]. EBioMedicine, 2016, 9: 356–365
WANG F, PENG C, ZHANG G Y, et al. Delayed kidney injury following coronary angiography [J]. Experimental and Therapeutic Medicine, 2016, 12(1): 530–534.
WANG F, ZHANG G Y, LU Z Y, et al. Antithrombin III/SerpinC1 insufficiency exacerbates renal ischemia/reperfusion injury [J]. Kidney International, 2015, 88(4): 796–803.
SCARPIONI L, DALL’AGLIO P P, POISETTI P G, et al. Retinol binding protein in serum and in urine of glomerular and tubular nephropathies [J]. Clinica Chimica Acta, 1976, 68(2): 107–113.
KELLEHER J, HUMPHREY C S, HOMER D, et al. Vitamin A and its transport proteins in patients with chronic renal failure receiving maintenance haemodialysis and after renal transplantation [J]. Clinical Science, 1983, 65(6): 619–626.
BERNARD A, VYSKOCYL A, MAHIEU P, et al. Effect of renal insufficiency on the concentration of free retinol-binding protein in urine and serum [J]. Clinica Chimica Acta, 1988, 171(1): 85–93.
AYATSE J O. Human retinol-binding protein: Its relationship to renal function in renal diseases [J]. West African Journal of Medicine, 1991, 10(3/4): 226–231.
LEE D C, LEE J W, IM J A. Association of serum retinol binding protein 4 and insulin resistance in apparently healthy adolescents [J]. Metabolism Clinical and Experimental, 2007, 56(3): 327–331.
BALAGOPAL P, GRAHAM T E, KAHN B B, et al. Reduction of elevated serum retinol binding protein in obese children by lifestyle intervention: Association with subclinical inflammation [J]. The Journal of Clinical Endocrinology & Metabolism, 2007, 92(5): 1971–1974.
LEVEY A S, CORESH J, BALK E, et al. K/DOQI clinical practice guidelines for chronic kidney disease: Evaluation, classification, and stratification [J]. Annals of Internal Medicine, 2003, 139(2): 137–147.
LU Z Y, YIN J Y, BAO H D, et al. Coexistence of acute crescent glomerulonephritis and IgG4-related kidney disease [J]. Case Rep Nephrol Dial, 2016, 6(2): 89–95.
CHEN B, TANG J, LU Z Y, et al. Primary cutaneous nocardiosis in a patient with nephrotic syndrome: A case report and review of the literature [J]. Medicine (Baltimore), 2016, 95(3), e2490.
WANG F, ZHANG G Y, XING T, et al. Renalase contributes to the renal protection of delayed ischaemic preconditioning via the regulation of hypoxia-inducible factor-1alpha [J]. Journal of Cellular and Molecular Medicine, 2015, 19(6): 1400–1409.
DONADIO C, LUCCHESI A, ARDINI M, et al. Cystatin C, ß2-microglobulin, and retinol-binding protein as indicators of glomerular filtration rate: Comparison with plasma creatinine [J]. Journal of Pharmaceutical and Biomedical Anallysis, 2001, 24(5/6): 835–842.
FREY S K, NAGL B, HENZE A, et al. Isoforms of retinol binding protein 4 (RBP4) are increased in chronic diseases of the kidney but not of the liver [J]. Lipids in Health and Disease, 2008, 7: 29.
SMITH F R, GOODMAN D S. The effects of diseases of the liver, thyroid, and kidneys on the transport of vitamin A in human plasma [J]. The Journal of Clinical Investigation, 1971, 50(11): 2426–2436.
MOGIELNICKI R P, WALDMANN T A, STROBER W. Renal handling of low molecular weight proteins. I. L-chain metabolism in experimental renal disease [J]. The Journal of Clinical Investigation, 1971, 50(4): 901–909.
YIN J Y, LU Z Y, WANG F, et al. Renalase attenuates hypertension, renal injury and cardiac remodelling in rats with subtotal nephrectomy [J]. Journal of Cellular and Molecular Medicine, 2016, 20(6): 1106–1117.
GERLACH T H, ZILE M H. Upregulation of serum retinol in experimental acute renal failure [J]. The FASEB Journal, 1990, 4(8): 2511–2517.
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Foundation item: the National Natural Science Foundation of China (Nos. 81570603, 81270824 and 81670632), the New-100 Talent Plan of Shanghai Jiao Tong University School of Medicine, the Shanghai Talents Development Fund (No. 201350) and the Shanghai Pujiang Talent Projects (No. 15PJ1406700)
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Lu, Z., Zhang, G., Xie, Y. et al. Serum levels of RBP4 might not be determined by diabetes mellitus but by kidney function and renal replacement therapy. J. Shanghai Jiaotong Univ. (Sci.) 21, 757–762 (2016). https://doi.org/10.1007/s12204-016-1791-3
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DOI: https://doi.org/10.1007/s12204-016-1791-3
Key words
- chronic kidney disease (CKD)
- retinol binding protein 4 (RBP4)
- renal replacement therapy
- diabetes mellitus (DM)