ВЗАИМОСВЯЗЬ ИНТЕРЛЕЙКИНА-6 И КОМПОНЕНТОВ КАРДИОРЕНАЛЬНОГО АНЕМИЧЕСКОГО СИНДРОМА ПРИ ДИАБЕТИЧЕСКОЙ НЕФРОПАТИИ*

Пчелин Иван Юрьевич; Наталья Валерьевна Худякова; Александр Николаевич Шишкин

doi:10.21638/11701/spbu11.2016.201

Authors

Пчелин Иван Юрьевич St. Petersburg State University, 7–9, Universitetskaya nab., St. Petersburg, 199034, Russian Federation
Наталья Валерьевна Худякова St. Petersburg State University, 7–9, Universitetskaya nab., St. Petersburg, 199034, Russian Federation
Александр Николаевич Шишкин St. Petersburg State University, 7–9, Universitetskaya nab., St. Petersburg, 199034, Russian Federation

DOI:

https://doi.org/10.21638/11701/spbu11.2016.201

Abstract

Diabetic nephropathy is a common complication of diabetes mellitus with a negative prognostic value.
Currently, there are no doubts that infl ammation has a pathogenic role not only in the development of diabetic kidney disease but in the formation of all of the characteristics of cardiorenal anemia syndrome. The aim of the study was to assess the clinical signifi cance of interleukin-6 evaluation in patients with diabetic nephropathy. We investigated 127 patients with type 2 diabetes mellitus complicated with chronic kidney disease stages 1–3. Th e results of the study indicate that serum concentration The study was supported by the President Grant for Government Support of Young Russian Scientists of interleukin-6 correlates negatively with hemoglobin level and estimated glomerular fi ltration rate. Meanwhile, it has no clear relationship with age, sex, treatment modality, body mass index, urinary albumin excretion and echocardiography data. In this paper we discuss the causes and the eff ects of elevated interleukin-6 production in patients with diabetic nephropathy. Further avenues of research are proposed. Refs 25. Figs 1. Table 2.

Keywords:

diabetic nephropathy, interleukin-6, inflammation, anemia

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References

Литература

International Diabetes Federation. IDF Diabetes Atlas update poster, 6th edn. Brussels, Belgium: International Diabetes Federation, 2014.

Шестакова М. В., Шамхалова М. Ш., Ярек-Мартынова И. Я. и др. Сахарный диабет и хроническая болезнь почек: достижения, нерешенные проблемы и перспективы лечения // Сахарный диабет. 2011. № 1. С. 81–88.

Viberti G., Wheeldon N. M. Microalbuminuria reduction with valsartan in patients with type 2 diabetes mellitus: A blood pressure independent effect // Circulation. 2002. Vol. 106. P. 672–678.

Karalliedde J., Gnudi L. ACCORD and ADVANCE: A tale of two studies on the merits of glycaemic control in type 2 diabetic patients // Nephrol. Dial. Transplant. 2008. Vol. 23. P. 1796–1798.

Chaturvedi N. Randomised placebo-controlled trial of lisinopril in normotensive patients with insulin-dependent diabetes and normoalbuminuria or microalbuminuria // Lancet. 1997. Vol. 349. P. 1787–1792.

Rivero A., Mora C., Muros M. et al. Pathogenic perspectives for the role of infl ammation in diabetic nephropathy // Clin. Sci. 2009. Vol. 116, N 6. P. 479–492.

Wada J., Makino H. Infl ammation and the pathogenesis of diabetic nephropathy // Clin. Sci. 2013. Vol. 124, N 3. P. 139–152.

Fornoni A., Ijaz A., Tejada T. et al. Role of Infl ammation in Diabetic Nephropathy // Curr. Diab. Rev. 2008. Vol. 4. P. 10–17.

Navarro-Gonzalez J. F., Mora-Fernandez C. The Role of Infl ammatory Cytokines in Diabetic Nephropathy // J. Am. Soc. Nephrol. 2008. Vol. 19. P. 433–442.

Ray A., Huisman M. V., Tamsma J. T. et al. Th e role of infl ammation on atherosclerosis, intermediate and clinical cardiovascular endpoints in type 2 diabetes mellitus // Eur. J. Int. Med. 2009. Vol. 20. P. 253–260.

Пчелин И. Ю., Шишкин А. Н. Механизмы развития и клиническое значение анемии у пациентов с сахарным диабетом 1 и 2 типа // Вестн. С.-Петерб. ун-та. Сер. 11. 2010. № 2. С. 73–80.

Kaul K., Hodgkinson A., Tarr J. M. Is inflammation a common retinal-renal-nerve pathogenic link in diabetes? // Curr. Diab. Rev. 2010. Vol. 6. P. 294–303.

Navarro J. F., Milena F. J., Mora C. et al. Renal pro-infl ammatory cytokine gene expression in diabetic nephropathy: eff ect of angiotensin-converting enzyme inhibition and pentoxifylline administration // Am. J. Nephrol. 2007. Vol. 26, N 6. P. 562–570.

Пчелин И. Ю., Шишкин А. Н., Лаптева О. А. Роль системного и локального воспаления в развитии диабетической нефропатии // Нефрология. 2011. Т. 15, № 4. С. 21–26.

Meléndez G. C., McLarty J. L., Levick S. P. et al. Interleukin 6 mediates myocardial fi brosis, concentric hypertrophy, and diastolic dysfunction in rats // Hypertension. 2010. Vol. 56, N 2. P. 225–231.

Jiang F., Sun Z.-Z., Tang Y.-T. et al. Hepcidin expression and iron parameters change in type 2 diabetic patients // Diabetes Res. Clin. Pract. 2011. Vol. 93. P. 43–48.

Choudhary N., Ahlawat R. S. Interleukin-6 and C-reactive protein in pathogenesis of diabetic nephropathy: new evidence linking infl ammation, glycemic control, and microalbuminuria // Iran. J. Kidney Dis. 2008. Vol. 2, N 2. P. 72–79.

Papaoikonomou S., Tentolouris N., Tousoulis D. et al. Th e association of the 174G > C polymorphism of interleukin 6 gene with diabetic nephropathy in patients with type 2 diabetes mellitus // J. Diabetes Compllications. 2013. Vol. 27, N 6. P. 576–579.

Kitamura A., Hasegawa G., Obayashi H. et al. Interleukin-6 polymorphism (-634C/G) in the promotor region and the progression of diabetic nephropathy in Type 2 diabetes // Diabet. Med. 2002. Vol. 19, N 12. P. 1000–1005.

Devaraj S., Venugopal S. K., Singh U., Jialal I. Hyperglycemia induces monocytic release of interleukin-6 via induction of protein kinase C-α and –β // Diabetes. 2004. Vol. 54, N 1. P. 85–91.

Andersson C. X., Sopasakis V. R., Wallerstedt E., Smith U. Insulin antagonizes interleukin-6 signaling and is anti-infl ammatory in 3T3-L1 adipocytes // J. Biol. Chem. 2007. Vol. 282, N 13. P. 9430–9435.

Andreozzi F., Laratta E., Procopio C. et al. Interleukin-6 impairs the insulin signaling pathway, promoting production of nitric oxide in human umbilical vein endothelial cells // Mol. Cell. Biol. 2007. Vol. 27,N 6. P. 2372–2383.

Lankhorst C. E., Wish J. B. Anemia in renal disease: Diagnosis and management // Blood Rev. 2010. Vol. 24. P. 39–47.

Otto C., Engelschalk C., Fraunberger P. et al. Lack of an association of urinary albumin excretion with interleukin-6 or C-reactive protein in patients with type 2 diabetes // Acta Diabetol. 2001. Vol. 38, N 4. P. 153–155.

Sahakyan K., Klein B. E. K., Lee K. E. et al. Infl ammatory and endothelial dysfunction markers and proteinuria in persons with type 1 diabetes mellitus // Eur. J. Endocrinol. 2010. Vol. 162, N 6. P. 1101–1105.

References

International Diabetes Federation. IDF Diabetes Atlas update poster, 6th edn. Brussels, Belgium, International Diabetes Federation, 2014.

Shestakova M. V., Shamkhalova M. Sh., Iarek-Martynova I. Ia. i dr. Sakharnyi diabet i khronicheskaia bolezn’ pochek: dostizheniia, nereshennye problemy i perspektivy lecheniia [Diabetes mellitus and chronic kidney disease: advances, unsolved problems and perspectives of treatment]. Sakharnyi diabet [Diabetes mellitus], 2011, no. 1, pp. 81–88. (In Russian)

Viberti G., Wheeldon N. M. Microalbuminuria reduction with valsartan in patients with type 2 diabetes mellitus: A blood pressure independent eff ect. Circulation, 2002, vol. 106, pp. 672–678.

Karalliedde J., Gnudi L. ACCORD and ADVANCE: A tale of two studies on the merits of glycaemic control in type 2 diabetic patients. Nephrol. Dial. Transplant., 2008, vol. 23, pp. 1796–1798.

Chaturvedi N. Randomised placebo-controlled trial of lisinopril in normotensive patients with insulin-dependent diabetes and normoalbuminuria or microalbuminuria. Lancet, 1997, vol. 349, pp. 1787–1792.

Rivero A., Mora C., Muros M. et al. Pathogenic perspectives for the role of infl ammation in diabetic nephropathy. Clin. Sci., 2009, vol. 116, no. 6, pp. 479–492.

Wada J., Makino H. Infl ammation and the pathogenesis of diabetic nephropathy. Clin. Sci., 2013,vol. 124, no. 3, pp. 139–152.

Fornoni A., Ijaz A., Tejada T. et al. Role of Infl ammation in Diabetic Nephropathy. Curr. Diab. Rev.,2008, vol. 4, pp. 10–17.

Navarro-Gonzalez J. F., Mora-Fernandez C. The Role of Infl ammatory Cytokines in Diabetic Nephropathy.J. Am. Soc. Nephrol., 2008, vol. 19, pp. 433–442.

Ray A., Huisman M. V., Tamsma J. T. et al. The role of infl ammation on atherosclerosis, intermediate and clinical cardiovascular endpoints in type 2 diabetes mellitus. Eur. J. Int. Med., 2009, vol. 20, pp. 253–260.

Pchelin I. Iu., Shishkin A. N. Mekhanizmy razvitiia i klinicheskoe znachenie anemii u patsientov s sakharnym diabetom 1 i 2 tipa [Mechanisms of development and clinical signifi cance of anemia in patients with type 1 and type 2 diabetes mellitus]. Vestnik of St. Petersburg University. Series 11. Medicine, 2010, no. 2, pp. 73–80. (In Russian)

Kaul K., Hodgkinson A., Tarr J. M. Is infl ammation a common retinal-renal-nerve pathogenic link in diabetes? Curr. Diab. Rev., 2010, vol. 6, pp. 294–303.

Navarro J. F., Milena F. J., Mora C. et al. Renal pro-infl ammatory cytokine gene expression in diabetic nephropathy: eff ect of angiotensin-converting enzyme inhibition and pentoxifylline administration. Am. J. Nephrol., 2007, vol. 26, no. 6, pp. 562–570.

Pchelin I. Iu., Shishkin A. N., Lapteva O. A. Rol’ sistemnogo i lokal’nogo vospaleniia v razvitii diabeticheskoi nefropatii [Th e role of systemic and local infl ammation in development of diabetic nephropathy].Nefrologiia [Nephrology], 2011, vol. 15, no. 4, pp. 21–26. (In Russian)

Meléndez G. C., McLarty J. L., Levick S. P. et al. Interleukin 6 mediates myocardial fi brosis, concentric hypertrophy, and diastolic dysfunction in rats. Hypertension, 2010, vol. 56, no. 2, pp. 225–231.

Jiang F., Sun Z.-Z., Tang Y.-T. et al. Hepcidin expression and iron parameters change in type 2 diabetic patients. Diabetes Res. Clin. Pract., 2011, vol. 93, pp. 43–48.

Choudhary N., Ahlawat R. S. Interleukin-6 and C-reactive protein in pathogenesis of diabetic nephropathy: new evidence linking infl ammation, glycemic control, and microalbuminuria. Iran. J. Kidney Dis., 2008, vol. 2, no. 2, pp. 72–79.

Papaoikonomou S., Tentolouris N., Tousoulis D. et al. Th e association of the 174G > C polymorphism of interleukin 6 gene with diabetic nephropathy in patients with type 2 diabetes mellitus. J. Diabetes Compllications, 2013, vol. 27, no. 6, pp. 576–579.

Kitamura A., Hasegawa G., Obayashi H. et al. Interleukin-6 polymorphism (-634C/G) in the promotor region and the progression of diabetic nephropathy in Type 2 diabetes. Diabet. Med., 2002, vol. 19,no. 12, pp. 1000–1005.

Devaraj S., Venugopal S. K., Singh U., Jialal I. Hyperglycemia induces monocytic release of interleukin-6 via induction of protein kinase C-α and –β. Diabetes, 2004, vol. 54, no. 1, pp. 85–91.

Andersson C. X., Sopasakis V. R., Wallerstedt E., Smith U. Insulin antagonizes interleukin-6 signaling and is anti-infl ammatory in 3T3-L1 adipocytes. J. Biol. Chem., 2007, vol. 282, no. 13, pp. 9430–9435.

Andreozzi F., Laratta E., Procopio C. et al. Interleukin-6 impairs the insulin signaling pathway, promoting production of nitric oxide in human umbilical vein endothelial cells. Mol. Cell. Biol., 2007, vol. 27,no. 6, pp. 2372–2383.

Lankhorst C. E., Wish J. B. Anemia in renal disease: Diagnosis and management. Blood Rev., 2010, vol. 24, pp. 39–47.

Otto C., Engelschalk C., Fraunberger P. et al. Lack of an association of urinary albumin excretion with interleukin-6 or C-reactive protein in patients with type 2 diabetes. Acta Diabetol., 2001, vol. 38, no. 4,pp. 153–155.

Sahakyan K., Klein B. E. K., Lee K. E. et al. Infl ammatory and endothelial dysfunction markers and proteinuria in persons with type 1 diabetes mellitus. Eur. J. Endocrinol., 2010, vol. 162, no. 6, pp. 1101–1105.