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Published in: BMC Endocrine Disorders 1/2018

Open Access 01-12-2018 | Research article

The ratio of AGE to sRAGE independently associated with albuminuria in hypertensive patients

Authors: Kuang-Hsing Chiang, Jaw-Wen Chen, Shao-Sung Huang, Hsin-Bang Leu, Shing-Jong Lin, Po-Hsun Huang

Published in: BMC Endocrine Disorders | Issue 1/2018

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Abstract

Background

Soluble receptor for advanced glycation end-products (sRAGE) and advanced glycation end-products (AGE) have been associated with risks of cardiovascular disease. Because sRAGE is regarded as a scavenger to AGE, we hypothesized that the ratio of AGE to sRAGE (AGE/sRAGE) is associated with albuminuria in hypertensive patients.

Methods

In this cross-sectional study, a total of 104 patients with essential hypertension were recruited. Hypertension was defined as a systolic blood pressure ≥ 140 mmHg, a diastolic blood pressure ≥ 90 mmHg, or use of antihypertensive treatment. Albuminuria was defined as albumin excretion rate ≧ 20 μg/min. Multivariate logistic regression analyses were performed to evaluate the association between AGE/sRAGE and albuminuria.

Results

Among the 104 patients, 30 (28.8%) patients had albuminuria and 74 (71.2%) patients did not. Patients with albuminuria had higher AGE (2.15 vs. 1.71 μg/mL), lower sRAGE (424.5 vs. 492.5 pg/ml) and higher AGE/sRAGE (3.79 vs. 3.29 μg/pg) than those without albuminuria. Multivariate logistic regression model revealed that AGE/sRAGE (OR = 1.131, 95% CI = 1.001–1.278, P = 0.048) was independently associated with albuminuria. There was no significant relationship between AGE and sRAGE alone with albuminuria.

Conclusion

This study suggests that the ratio of AGE to sRAGE may be a surrogate biomarker for microvascular injury. Further prospective studies of the prognostic value of the ratio in relation to microvasular injury are needed.
Literature
1.
go back to reference Pontremoli R. Microalbuminuria in essential hypertension--its relation to cardiovascular risk factors. Nephrol Dial Transplant. 1996;11(11):2113–5.CrossRef Pontremoli R. Microalbuminuria in essential hypertension--its relation to cardiovascular risk factors. Nephrol Dial Transplant. 1996;11(11):2113–5.CrossRef
2.
go back to reference Pontremoli R, Ravera M, Bezante GP, Viazzi F, Nicolella C, Berruti V, Leoncini G, Del Sette M, Brunelli C, Tomolillo C, et al. Left ventricular geometry and function in patients with essential hypertension and microalbuminuria. J Hypertens. 1999;17(7):993–1000.CrossRef Pontremoli R, Ravera M, Bezante GP, Viazzi F, Nicolella C, Berruti V, Leoncini G, Del Sette M, Brunelli C, Tomolillo C, et al. Left ventricular geometry and function in patients with essential hypertension and microalbuminuria. J Hypertens. 1999;17(7):993–1000.CrossRef
3.
go back to reference Leoncini G, Sacchi G, Ravera M, Viazzi F, Ratto E, Vettoretti S, Parodi D, Bezante GP, Del Sette M, Deferrari G, et al. Microalbuminuria is an integrated marker of subclinical organ damage in primary hypertension. J Hum Hypertens. 2002;16(6):399–404.CrossRef Leoncini G, Sacchi G, Ravera M, Viazzi F, Ratto E, Vettoretti S, Parodi D, Bezante GP, Del Sette M, Deferrari G, et al. Microalbuminuria is an integrated marker of subclinical organ damage in primary hypertension. J Hum Hypertens. 2002;16(6):399–404.CrossRef
4.
go back to reference Viazzi F, Leoncini G, Ratto E, Vaccaro V, Tomolillo C, Falqui V, Parodi A, Conti N, Deferrari G, Pontremoli R. Microalbuminuria, blood pressure load, and systemic vascular permeability in primary hypertension. Am J Hypertens. 2006;19(11):1183–9.CrossRef Viazzi F, Leoncini G, Ratto E, Vaccaro V, Tomolillo C, Falqui V, Parodi A, Conti N, Deferrari G, Pontremoli R. Microalbuminuria, blood pressure load, and systemic vascular permeability in primary hypertension. Am J Hypertens. 2006;19(11):1183–9.CrossRef
5.
go back to reference Jensen JS, Feldt-Rasmussen B, Strandgaard S, Schroll M, Borch-Johnsen K. Arterial hypertension, microalbuminuria, and risk of ischemic heart disease. Hypertension. 2000;35(4):898–903.CrossRef Jensen JS, Feldt-Rasmussen B, Strandgaard S, Schroll M, Borch-Johnsen K. Arterial hypertension, microalbuminuria, and risk of ischemic heart disease. Hypertension. 2000;35(4):898–903.CrossRef
6.
go back to reference Asselbergs FW, de Boer RA, Diercks GF, Langeveld B, Tio RA, de Jong PE, van Veldhuisen DJ, van Gilst WH. Vascular endothelial growth factor: the link between cardiovascular risk factors and microalbuminuria? Int J Cardiol. 2004;93(2–3):211–5.CrossRef Asselbergs FW, de Boer RA, Diercks GF, Langeveld B, Tio RA, de Jong PE, van Veldhuisen DJ, van Gilst WH. Vascular endothelial growth factor: the link between cardiovascular risk factors and microalbuminuria? Int J Cardiol. 2004;93(2–3):211–5.CrossRef
7.
go back to reference Heerspink HJ, Ninomiya T, Persson F, Brenner BM, Brunel P, Chaturvedi N, Desai AS, Haffner SM, McMurray JJ, Solomon SD, Pfeffer MA, Parving HH, de Zeeuw D. Is a reduction in albuminuria associated with renal and cardiovascular protection? A post hoc analysis of the ALTITUDE trial. Diabetes Obes Metab. 2016;18(2):169–77.CrossRef Heerspink HJ, Ninomiya T, Persson F, Brenner BM, Brunel P, Chaturvedi N, Desai AS, Haffner SM, McMurray JJ, Solomon SD, Pfeffer MA, Parving HH, de Zeeuw D. Is a reduction in albuminuria associated with renal and cardiovascular protection? A post hoc analysis of the ALTITUDE trial. Diabetes Obes Metab. 2016;18(2):169–77.CrossRef
8.
go back to reference Asselbergs FW, Hillege HL, van Gilst WH. Framingham score and microalbuminuria: combined future targets for primary prevention? Kidney Int Suppl. 2004;92:S111–4.CrossRef Asselbergs FW, Hillege HL, van Gilst WH. Framingham score and microalbuminuria: combined future targets for primary prevention? Kidney Int Suppl. 2004;92:S111–4.CrossRef
9.
go back to reference Stirban A, Gawlowski T, Roden M. Vascular effects of advanced glycation endproducts: clinical effects and molecular mechanisms. Mol Metab. 2014;3(2):94–108.CrossRef Stirban A, Gawlowski T, Roden M. Vascular effects of advanced glycation endproducts: clinical effects and molecular mechanisms. Mol Metab. 2014;3(2):94–108.CrossRef
10.
go back to reference Yamagishi S, Matsui T. Soluble form of a receptor for advanced glycation end products (sRAGE) as a biomarker. Front Biosci (Elite Ed). 2010;2:1184–95.CrossRef Yamagishi S, Matsui T. Soluble form of a receptor for advanced glycation end products (sRAGE) as a biomarker. Front Biosci (Elite Ed). 2010;2:1184–95.CrossRef
11.
go back to reference Park L, Raman KG, Lee KJ, Lu Y, Ferran LJ Jr, Chow WS, Stern D, Schmidt AM. Suppression of accelerated diabetic atherosclerosis by the soluble receptor for advanced glycation endproducts. Nat Med. 1998;4(9):1025–31.CrossRef Park L, Raman KG, Lee KJ, Lu Y, Ferran LJ Jr, Chow WS, Stern D, Schmidt AM. Suppression of accelerated diabetic atherosclerosis by the soluble receptor for advanced glycation endproducts. Nat Med. 1998;4(9):1025–31.CrossRef
12.
go back to reference Schmidt AM, Yan SD, Wautier JL, Stern D. Activation of receptor for advanced glycation end products: a mechanism for chronic vascular dysfunction in diabetic vasculopathy and atherosclerosis. Circ Res. 1999;84(5):489–97.CrossRef Schmidt AM, Yan SD, Wautier JL, Stern D. Activation of receptor for advanced glycation end products: a mechanism for chronic vascular dysfunction in diabetic vasculopathy and atherosclerosis. Circ Res. 1999;84(5):489–97.CrossRef
13.
go back to reference Fujisawa K, Katakami N, Kaneto H, Naka T, Takahara M, Sakamoto F, Irie Y, Miyashita K, Kubo F, Yasuda T, et al. Circulating soluble RAGE as a predictive biomarker of cardiovascular event risk in patients with type 2 diabetes. Atherosclerosis. 2013;227(2):425–8.CrossRef Fujisawa K, Katakami N, Kaneto H, Naka T, Takahara M, Sakamoto F, Irie Y, Miyashita K, Kubo F, Yasuda T, et al. Circulating soluble RAGE as a predictive biomarker of cardiovascular event risk in patients with type 2 diabetes. Atherosclerosis. 2013;227(2):425–8.CrossRef
14.
go back to reference Falcone C, Emanuele E, D'Angelo A, Buzzi MP, Belvito C, Cuccia M, Geroldi D. Plasma levels of soluble receptor for advanced glycation end products and coronary artery disease in nondiabetic men. Arterioscler Thromb Vasc Biol. 2005;25(5):1032–7.CrossRef Falcone C, Emanuele E, D'Angelo A, Buzzi MP, Belvito C, Cuccia M, Geroldi D. Plasma levels of soluble receptor for advanced glycation end products and coronary artery disease in nondiabetic men. Arterioscler Thromb Vasc Biol. 2005;25(5):1032–7.CrossRef
15.
go back to reference Hanssen NM, Beulens JW, van Dieren S, Scheijen JL, van der AD, Spijkerman AM, van der Schouw YT, Stehouwer CD, Schalkwijk CG. Plasma advanced glycation end products are associated with incident cardiovascular events in individuals with type 2 diabetes: a case-cohort study with a median follow-up of 10 years (EPIC-NL). Diabetes. 2015;64(1):257–65.CrossRef Hanssen NM, Beulens JW, van Dieren S, Scheijen JL, van der AD, Spijkerman AM, van der Schouw YT, Stehouwer CD, Schalkwijk CG. Plasma advanced glycation end products are associated with incident cardiovascular events in individuals with type 2 diabetes: a case-cohort study with a median follow-up of 10 years (EPIC-NL). Diabetes. 2015;64(1):257–65.CrossRef
16.
go back to reference Kizer JR, Benkeser D, Arnold AM, Ix JH, Mukamal KJ, Djousse L, Tracy RP, Siscovick DS, Psaty BM, Zieman SJ. Advanced glycation/glycoxidation endproduct carboxymethyl-lysine and incidence of coronary heart disease and stroke in older adults. Atherosclerosis. 2014;235(1):116–21.CrossRef Kizer JR, Benkeser D, Arnold AM, Ix JH, Mukamal KJ, Djousse L, Tracy RP, Siscovick DS, Psaty BM, Zieman SJ. Advanced glycation/glycoxidation endproduct carboxymethyl-lysine and incidence of coronary heart disease and stroke in older adults. Atherosclerosis. 2014;235(1):116–21.CrossRef
17.
go back to reference Busch M, Franke S, Wolf G, Brandstadt A, Ott U, Gerth J, Hunsicker LG, Stein G. The advanced glycation end product N(epsilon)-carboxymethyllysine is not a predictor of cardiovascular events and renal outcomes in patients with type 2 diabetic kidney disease and hypertension. Am J Kidney Dis. 2006;48(4):571–9.CrossRef Busch M, Franke S, Wolf G, Brandstadt A, Ott U, Gerth J, Hunsicker LG, Stein G. The advanced glycation end product N(epsilon)-carboxymethyllysine is not a predictor of cardiovascular events and renal outcomes in patients with type 2 diabetic kidney disease and hypertension. Am J Kidney Dis. 2006;48(4):571–9.CrossRef
18.
go back to reference Prasad K. Low levels of serum soluble receptors for advanced glycation end products, biomarkers for disease state: myth or reality. Int J Angiol. 2014;23(1):11–6.CrossRef Prasad K. Low levels of serum soluble receptors for advanced glycation end products, biomarkers for disease state: myth or reality. Int J Angiol. 2014;23(1):11–6.CrossRef
19.
go back to reference Tahara N, Yamagishi S, Tahara A, Ishibashi M, Hayabuchi N, Takeuchi M, Imaizumi T. Adiponectin is inversely associated with ratio of serum levels of AGEs to sRAGE and vascular inflammation. Int J Cardiol. 2012;158(3):461–2.CrossRef Tahara N, Yamagishi S, Tahara A, Ishibashi M, Hayabuchi N, Takeuchi M, Imaizumi T. Adiponectin is inversely associated with ratio of serum levels of AGEs to sRAGE and vascular inflammation. Int J Cardiol. 2012;158(3):461–2.CrossRef
20.
go back to reference Tahara A, Tahara N, Yamagishi SI, Honda A, Igata S, Nitta Y, Bekki M, Nakamura T, Sugiyama Y, Sun J, et al. Ratio of serum levels of AGEs to soluble RAGE is correlated with trimethylamine-N-oxide in non-diabetic subjects. Int J Food Sci Nutr. 2017;68(8):1013–20.CrossRef Tahara A, Tahara N, Yamagishi SI, Honda A, Igata S, Nitta Y, Bekki M, Nakamura T, Sugiyama Y, Sun J, et al. Ratio of serum levels of AGEs to soluble RAGE is correlated with trimethylamine-N-oxide in non-diabetic subjects. Int J Food Sci Nutr. 2017;68(8):1013–20.CrossRef
21.
go back to reference Kajikawa M, Nakashima A, Fujimura N, Maruhashi T, Iwamoto Y, Iwamoto A, Matsumoto T, Oda N, Hidaka T, Kihara Y, et al. Ratio of serum levels of AGEs to soluble form of RAGE is a predictor of endothelial function. Diabetes Care. 2015;38(1):119–25.CrossRef Kajikawa M, Nakashima A, Fujimura N, Maruhashi T, Iwamoto Y, Iwamoto A, Matsumoto T, Oda N, Hidaka T, Kihara Y, et al. Ratio of serum levels of AGEs to soluble form of RAGE is a predictor of endothelial function. Diabetes Care. 2015;38(1):119–25.CrossRef
22.
go back to reference Prasad K, Dhar I, Zhou Q, Elmoselhi H, Shoker M, Shoker A. AGEs/sRAGE, a novel risk factor in the pathogenesis of end-stage renal disease. Mol Cell Biochem. 2016;423(1–2):105–14.CrossRef Prasad K, Dhar I, Zhou Q, Elmoselhi H, Shoker M, Shoker A. AGEs/sRAGE, a novel risk factor in the pathogenesis of end-stage renal disease. Mol Cell Biochem. 2016;423(1–2):105–14.CrossRef
23.
go back to reference Machahua C, Montes-Worboys A, Llatjos R, Escobar I, Dorca J, Molina-Molina M, Vicens-Zygmunt V. Increased AGE-RAGE ratio in idiopathic pulmonary fibrosis. Respir Res. 2016;17(1):144.CrossRef Machahua C, Montes-Worboys A, Llatjos R, Escobar I, Dorca J, Molina-Molina M, Vicens-Zygmunt V. Increased AGE-RAGE ratio in idiopathic pulmonary fibrosis. Respir Res. 2016;17(1):144.CrossRef
24.
go back to reference Cuccurullo C, Iezzi A, Fazia ML, De Cesare D, Di Francesco A, Muraro R, Bei R, Ucchino S, Spigonardo F, Chiarelli F, et al. Suppression of RAGE as a basis of simvastatin-dependent plaque stabilization in type 2 diabetes. Arterioscler Thromb Vasc Biol. 2006;26(12):2716–23.CrossRef Cuccurullo C, Iezzi A, Fazia ML, De Cesare D, Di Francesco A, Muraro R, Bei R, Ucchino S, Spigonardo F, Chiarelli F, et al. Suppression of RAGE as a basis of simvastatin-dependent plaque stabilization in type 2 diabetes. Arterioscler Thromb Vasc Biol. 2006;26(12):2716–23.CrossRef
25.
go back to reference Derosa G, Bonaventura A, Romano D, Bianchi L, Fogari E, D'Angelo A, Maffioli P. Effects of enalapril/lercanidipine combination on some emerging biomarkers in cardiovascular risk stratification in hypertensive patients. J Clin Pharm Ther. 2014;39(3):277–85.CrossRef Derosa G, Bonaventura A, Romano D, Bianchi L, Fogari E, D'Angelo A, Maffioli P. Effects of enalapril/lercanidipine combination on some emerging biomarkers in cardiovascular risk stratification in hypertensive patients. J Clin Pharm Ther. 2014;39(3):277–85.CrossRef
26.
go back to reference Falcone C, Buzzi MP, Bozzini S, Boiocchi C, D'Angelo A, Schirinzi S, Esposito C, Torreggiani M, Choi J, Ochan Kilama M, et al. Microalbuminuria and sRAGE in high-risk hypertensive patients treated with nifedipine/telmisartan combination treatment: a substudy of TALENT. Mediat Inflamm. 2012;2012:874149.CrossRef Falcone C, Buzzi MP, Bozzini S, Boiocchi C, D'Angelo A, Schirinzi S, Esposito C, Torreggiani M, Choi J, Ochan Kilama M, et al. Microalbuminuria and sRAGE in high-risk hypertensive patients treated with nifedipine/telmisartan combination treatment: a substudy of TALENT. Mediat Inflamm. 2012;2012:874149.CrossRef
27.
go back to reference Komiya N, Hirose H, Saisho Y, Saito I, Itoh H. Effects of 12-month valsartan therapy on glycation and oxidative stress markers in type 2 diabetic subjects with hypertension. Int Heart J. 2008;49(6):681–9.CrossRef Komiya N, Hirose H, Saisho Y, Saito I, Itoh H. Effects of 12-month valsartan therapy on glycation and oxidative stress markers in type 2 diabetic subjects with hypertension. Int Heart J. 2008;49(6):681–9.CrossRef
28.
go back to reference Engelen L, Persson F, Ferreira I, Rossing P, Hovind P, Teerlink T, Stehouwer CD, Parving HH, Schalkwijk CG. Irbesartan treatment does not influence plasma levels of the advanced glycation end products N(epsilon)(1-carboxymethyl)lysine and N(epsilon)(1-carboxyethyl)lysine in patients with type 2 diabetes and microalbuminuria. A randomized controlled trial. Nephrol Dial Transplant. 2011;26(11):3573–7.CrossRef Engelen L, Persson F, Ferreira I, Rossing P, Hovind P, Teerlink T, Stehouwer CD, Parving HH, Schalkwijk CG. Irbesartan treatment does not influence plasma levels of the advanced glycation end products N(epsilon)(1-carboxymethyl)lysine and N(epsilon)(1-carboxyethyl)lysine in patients with type 2 diabetes and microalbuminuria. A randomized controlled trial. Nephrol Dial Transplant. 2011;26(11):3573–7.CrossRef
29.
go back to reference Gugliucci A, Menini T. The axis AGE-RAGE-soluble RAGE and oxidative stress in chronic kidney disease. Adv Exp Med Biol. 2014;824:191–208.CrossRef Gugliucci A, Menini T. The axis AGE-RAGE-soluble RAGE and oxidative stress in chronic kidney disease. Adv Exp Med Biol. 2014;824:191–208.CrossRef
30.
go back to reference Quade-Lyssy P, Kanarek AM, Baiersdorfer M, Postina R, Kojro E. Statins stimulate the production of a soluble form of the receptor for advanced glycation end products. J Lipid Res. 2013;54(11):3052–61.CrossRef Quade-Lyssy P, Kanarek AM, Baiersdorfer M, Postina R, Kojro E. Statins stimulate the production of a soluble form of the receptor for advanced glycation end products. J Lipid Res. 2013;54(11):3052–61.CrossRef
31.
go back to reference Rabbani N, Adaikalakoteswari A, Rossing K, Rossing P, Tarnow L, Parving HH, Thornalley PJ. Effect of Irbesartan treatment on plasma and urinary markers of protein damage in patients with type 2 diabetes and microalbuminuria. Amino Acids. 2012;42(5):1627–39.CrossRef Rabbani N, Adaikalakoteswari A, Rossing K, Rossing P, Tarnow L, Parving HH, Thornalley PJ. Effect of Irbesartan treatment on plasma and urinary markers of protein damage in patients with type 2 diabetes and microalbuminuria. Amino Acids. 2012;42(5):1627–39.CrossRef
Metadata
Title
The ratio of AGE to sRAGE independently associated with albuminuria in hypertensive patients
Authors
Kuang-Hsing Chiang
Jaw-Wen Chen
Shao-Sung Huang
Hsin-Bang Leu
Shing-Jong Lin
Po-Hsun Huang
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Endocrine Disorders / Issue 1/2018
Electronic ISSN: 1472-6823
DOI
https://doi.org/10.1186/s12902-018-0306-7

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