nefrНефрологияNephrology (Saint-Petersburg)1561-62742541-9439Pavlov First Saint-Petersburg State Medical Universitynefr-85Research ArticleОБЗОРЫ И ЛЕКЦИИREVIEWS AND LECTURESДиабетическая нефропатия - фокус на повреждение подоцитовDiabetic nephropathy - focus on podocytes damageБобковаИ. Н.BobkovaI. N.irbo.mma@mail.ruШестаковаМ. В.ShestakovaM. V.noemail@neicon.ruЩукинаА. А.SchukinaA. A.noemail@neicon.ruНаучно-исследовательский институт профессионального образования; Первый Московский государственный медицинский университет им. И.М. СеченоваРоссияI.M.Sechenov First Moscow State Medical UniversityRussian FederationЭндокринологический научный центрРоссияEndocrinologically research centerRussian FederationПервый Московский государственный медицинский университет им. И.М. СеченоваРоссияI.M.Sechenov First Moscow State Medical UniversityRussian Federation2015010320151923344Copyright © Бобкова И.Н., Шестакова М.В., Щукина А.А., 20152015Бобкова И.Н., Шестакова М.В., Щукина А.А.Bobkova I.N., Shestakova M.V., Schukina A.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.nephrolog.ru/jour/article/view/85

В настоящем обзоре подробно рассмотрены механизмы повреждения подоцитов при сахарном диабете, их взаимосвязь с метаболическими и гемодинамическими нарушениями, представлены результаты последних экспериментальных и клинических исследований по данным вопросам. Авторами освещены биомаркеры, отражающие выраженность подоцитарной дисфункции и структурно-функциональных изменений в нефроне при диабетической нефропатии, обсуждены современные возможности коррекции данных нарушений с целью предупреждения прогрессирования поражения почек.

Present review describes the mechanisms of podocytes damage at diabetes, their relationship with metabolic and hemodynamic disorders, the results of recent experimental and clinical studies on these issues are presented. The authors present biomarkers reflecting the intensity of podocyturia dysfunction and structural-functional changes in the nephron in diabetic nephropathy, modern opportunities of such disorders correction to prevent the progression of kidney injury are discussed.

подоцитыдиабетическая нефропатияподоцитопатиянефринурияподоцитопенияпротеинуриямикроальбуминуриягломерулосклерознефропротекцияpodocytesdiabetic nephropathypodocytopenianephrinuriapodocytopeniaproteinuriamicroalbuminuriaglomerulosclerosisnephroprotectionReferencesДедов И.И. Сахарный диабет: развитие технологий в диагностике, лечении и профилактике (пленарная лекция). Сахарный диабет 2010; 3: 6-12 [Dedov I.I. Saharny'i' diabet: razvitie tekhnologii' v diagnostike, lechenii i profilaktike (plenarnaia lektciia). Saharny'i' diabet 2010; 3: 6-12]Дедов И.И. Сахарный диабет: развитие технологий в диагностике, лечении и профилактике (пленарная лекция). Сахарный диабет 2010; 3: 6-12 [Dedov I.I. Saharny'i' diabet: razvitie tekhnologii' v diagnostike, lechenii i profilaktike (plenarnaia lektciia). Saharny'i' diabet 2010; 3: 6-12]Шамхалова М.Ш., Трубицына Н.П., Шестакова М.В. Новые перспективы терапии пациентов с сахарным диабетом 2 типа. Сахарный диабет 2012; 4: 109-114 [Shamhalova M.Sh., Trubitcy'na N.P., Shestakova M.V. Novy'e perspektivy' terapii patcientov s saharny'm diabetom 2 tipa. Saharny'i' diabet 2012; 4: 109-114Шамхалова М.Ш., Трубицына Н.П., Шестакова М.В. Новые перспективы терапии пациентов с сахарным диабетом 2 типа. Сахарный диабет 2012; 4: 109-114 [Shamhalova M.Sh., Trubitcy'na N.P., Shestakova M.V. Novy'e perspektivy' terapii patcientov s saharny'm diabetom 2 tipa. Saharny'i' diabet 2012; 4: 109-114Лебедева Н.О., Викулова О.К. Маркеры доклинической диагностики диабетической нефропатии у пациентов с сахарным диабетом 1 типа. Сахарный диабет 2012; 2: 38-45 [Lebedeva N.O., Vikulova O.K. Markery' doclinicheskoi' diagnostiki diabeticheskoi' nefropatii u patcientov s saharny'm diabetom 1 tipa. Saharny'i' diabet 2012; 2: 38-45]Лебедева Н.О., Викулова О.К. Маркеры доклинической диагностики диабетической нефропатии у пациентов с сахарным диабетом 1 типа. Сахарный диабет 2012; 2: 38-45 [Lebedeva N.O., Vikulova O.K. Markery' doclinicheskoi' diagnostiki diabeticheskoi' nefropatii u patcientov s saharny'm diabetom 1 tipa. Saharny'i' diabet 2012; 2: 38-45]International Diabetes Federation. Diabetes Atlas. Sixth edition; 2013International Diabetes Federation. Diabetes Atlas. Sixth edition; 2013Дедов И.И., Шестакова М.В. Сахарный диабет и хроническая болезнь почек. Медицинское информационное агентство, М., 2009 [Dedov I.I., Shestakova M.V. Saharny'i' diabet i khronicheskaia bolezn' pochek. Meditcinskoe informatcionnoe agentstvo, M., 2009]Дедов И.И., Шестакова М.В. Сахарный диабет и хроническая болезнь почек. Медицинское информационное агентство, М., 2009 [Dedov I.I., Shestakova M.V. Saharny'i' diabet i khronicheskaia bolezn' pochek. Meditcinskoe informatcionnoe agentstvo, M., 2009]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: 81-88 [6. Shestakova M.V., Shamhalova M.Sh., Iarek-Marty'nova I.I. A i dr. Saharny'i' diabet i khronicheskaia bolezn' pochek: dostizheniia, nereshenny'e problemy' i perspektivy' lecheniia. Saharny'i' diabet 2011; 1: 81-88]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: 81-88 [6. Shestakova M.V., Shamhalova M.Sh., Iarek-Marty'nova I.I. A i dr. Saharny'i' diabet i khronicheskaia bolezn' pochek: dostizheniia, nereshenny'e problemy' i perspektivy' lecheniia. Saharny'i' diabet 2011; 1: 81-88]Granier C., Makni K., Molina L. et al. Gene and protein markers of diabetic nephropathy. Nephrol Dial Transplant 2008; 23: 7922-8799Granier C., Makni K., Molina L. et al. Gene and protein markers of diabetic nephropathy. Nephrol Dial Transplant 2008; 23: 7922-8799Caramori M.L., Fioretto P., Mauer M. The need for early predictors of diabetic nephropathy risk: is albumin excretion rate sufficient? Diabetes 2000; 49: 1399-1408Caramori M.L., Fioretto P., Mauer M. The need for early predictors of diabetic nephropathy risk: is albumin excretion rate sufficient? Diabetes 2000; 49: 1399-1408Shankland S.J. Podocyte's response to injury: role in proteinuria and sclerosis. Kidney Int 2006; 69: 2131-2147Shankland S.J. Podocyte's response to injury: role in proteinuria and sclerosis. Kidney Int 2006; 69: 2131-2147Kimmelstiel P., Wilson C. Intercapillary lesion in the glomeruli of the kidney. Am J Pathol 1936; 12: 82-97Kimmelstiel P., Wilson C. Intercapillary lesion in the glomeruli of the kidney. Am J Pathol 1936; 12: 82-97Stitt-Cavanagh E., MacLeod L., Kennedy C.R.J. The podocyte in diabetic kidney disease. The Scientific World Journal 2009; 9: 1127-1139Stitt-Cavanagh E., MacLeod L., Kennedy C.R.J. The podocyte in diabetic kidney disease. The Scientific World Journal 2009; 9: 1127-1139Reddy G.R., Kotlyarevska K., Ransom R.F. The podocyte and diabetes mellitus: is the podocyte key to the origins of diabetic nephropathy? Curr Opin Nephrol Hypertens 2008; 17: 32-36Reddy G.R., Kotlyarevska K., Ransom R.F. The podocyte and diabetes mellitus: is the podocyte key to the origins of diabetic nephropathy? Curr Opin Nephrol Hypertens 2008; 17: 32-36Wolf G., Chen S., Ziyadeh F.N. From the periphery of glomerular capillary wall toward the center of disease. Podocyte injury comes of age in diabetic nephropathy. Diabetes 2005; 54(6): 1626-1634Wolf G., Chen S., Ziyadeh F.N. From the periphery of glomerular capillary wall toward the center of disease. Podocyte injury comes of age in diabetic nephropathy. Diabetes 2005; 54(6): 1626-1634Ziyadeh F.N., Wolf G. Pathogenesis of podocytopathy and proteiuria in diabetic glomerulopathy. Current Diabetes Reviews 2008; 4: 39-45Ziyadeh F.N., Wolf G. Pathogenesis of podocytopathy and proteiuria in diabetic glomerulopathy. Current Diabetes Reviews 2008; 4: 39-45Steffes M.W., Schmidt D., McGregory R., Basgen J.M. Glomerular cell number in normal subject and in type 1diabetic patients. Kidney Int 2001; 59: 2104-2113Steffes M.W., Schmidt D., McGregory R., Basgen J.M. Glomerular cell number in normal subject and in type 1diabetic patients. Kidney Int 2001; 59: 2104-2113Pätäri A., Forsblom C., Havana M. et al. Nephrinuria in diabetic nephropathy of type 1 diabetes. Diabetes 2003; 52: 2969-2974Pätäri A., Forsblom C., Havana M. et al. Nephrinuria in diabetic nephropathy of type 1 diabetes. Diabetes 2003; 52: 2969-2974Lewko B., Stepinski J. Hypergliycemia and mechanical stress: Targeting the renal podocyte. J Cell Physiol 2009; 221(2): 288-295Lewko B., Stepinski J. Hypergliycemia and mechanical stress: Targeting the renal podocyte. J Cell Physiol 2009; 221(2): 288-295Diez-Sampedro A., Lenz O., Fornoni A. Podocytopathy in diabetes: a metabolic and endocrine disorder. Am J Kidney Dis 2011; 58(4): 637-646Diez-Sampedro A., Lenz O., Fornoni A. Podocytopathy in diabetes: a metabolic and endocrine disorder. Am J Kidney Dis 2011; 58(4): 637-646Vestra M.D., Masiero A., Roiter A.M. et al. Is podocyte injury relevant in diabetic nephropathy? Studies in patients with type 2 diabetes. Diabetes 2003; 52: 1031-1035Vestra M.D., Masiero A., Roiter A.M. et al. Is podocyte injury relevant in diabetic nephropathy? Studies in patients with type 2 diabetes. Diabetes 2003; 52: 1031-1035Nakatsue T., Koike H., Han G.D. et al. Nephrin and podocin dissociate at the onset of proteinuria in experimental membranous nephropathy. Kidney Int 2005; 67: 2239-2253Nakatsue T., Koike H., Han G.D. et al. Nephrin and podocin dissociate at the onset of proteinuria in experimental membranous nephropathy. Kidney Int 2005; 67: 2239-2253Huh W., Kim D.J., Kim M.-K. et al. Expression of nephrin in acquired human glomerular disease. Nephrol Dial Transplant 2002; 17: 478-484Huh W., Kim D.J., Kim M.-K. et al. Expression of nephrin in acquired human glomerular disease. Nephrol Dial Transplant 2002; 17: 478-484Ng D.P.K., Tai B.C., Tan E. et al. Nephrinuria associates with multiple renal traits in type 2 diabetes. Nephrol Dial Transplant. 2010; 26: 2508-2514.Ng D.P.K., Tai B.C., Tan E. et al. Nephrinuria associates with multiple renal traits in type 2 diabetes. Nephrol Dial Transplant. 2010; 26: 2508-2514.Jim B., Ghanta M., Qipo A. et al. Dysregulated nephrin in diabetic nephropathy of type 2 diabetes: A cross Sectional study. PLoS ONE 2012; 7(5): e36041Jim B., Ghanta M., Qipo A. et al. Dysregulated nephrin in diabetic nephropathy of type 2 diabetes: A cross Sectional study. PLoS ONE 2012; 7(5): e36041Doublier S., Salvidio G., Lupia E. et al. Nephrin expression is reduced in human diabetic nephropathy of type 1 diabetes. Diabetes 2003; 52: 2969-2974Doublier S., Salvidio G., Lupia E. et al. Nephrin expression is reduced in human diabetic nephropathy of type 1 diabetes. Diabetes 2003; 52: 2969-2974Koop K., Eikhmans M., Baelde H.J. et al. Expression of podocyte-associated molecules in acquired human kidney diseases. Am J Soc Nephrol 2003; 14: 2063-2071Koop K., Eikhmans M., Baelde H.J. et al. Expression of podocyte-associated molecules in acquired human kidney diseases. Am J Soc Nephrol 2003; 14: 2063-2071Benigni A., Gagliardini E., Tomasoni S. et al. Selective impairment of gene expression and assembly of nephrin in human diabetic nephropathy. Kidney Int 2004; 65: 2193-2200Benigni A., Gagliardini E., Tomasoni S. et al. Selective impairment of gene expression and assembly of nephrin in human diabetic nephropathy. Kidney Int 2004; 65: 2193-2200Chen H.C., Chen C.A., Guh J.Y. et al. Altering expression of alpha3beta1 integrin on podocytes of human and rats with diabetes. Life Sci 2000; 67: 2345-2353Chen H.C., Chen C.A., Guh J.Y. et al. Altering expression of alpha3beta1 integrin on podocytes of human and rats with diabetes. Life Sci 2000; 67: 2345-2353Regoli M., Bendayan M. Alteration in the expression of alpha3beta1 integrin in certain membrane domains of the glomerular epithelial cells (podocytes) in diabetes mellitus. Diabetologia 1997; 40: 15-22Regoli M., Bendayan M. Alteration in the expression of alpha3beta1 integrin in certain membrane domains of the glomerular epithelial cells (podocytes) in diabetes mellitus. Diabetologia 1997; 40: 15-22Nakamura T., Ushiyama C., Suzuki S. et al. Urinary excretion of podocytes in patients with diabetic nephropathy. Nephrol Dial Transplant 2000; 15: 1379-1383Nakamura T., Ushiyama C., Suzuki S. et al. Urinary excretion of podocytes in patients with diabetic nephropathy. Nephrol Dial Transplant 2000; 15: 1379-1383Wogelmann S.U., Nelson W.J., Myers B.D. et al. Urinary excretion of podocytes in health and renal disease. Am J Physiol Renal Physiol 2003; 285: F40-F48Wogelmann S.U., Nelson W.J., Myers B.D. et al. Urinary excretion of podocytes in health and renal disease. Am J Physiol Renal Physiol 2003; 285: F40-F48Sanches-Nino M.D., Sanz A.B., Sanches-Lopes E. et al. HSP27 / HSPB1 as an adaptive podocyte antiapoptotic protein activated by high glucose and angiotensin II. Laboratory Investigation 2012; 92: 32-45Sanches-Nino M.D., Sanz A.B., Sanches-Lopes E. et al. HSP27 / HSPB1 as an adaptive podocyte antiapoptotic protein activated by high glucose and angiotensin II. Laboratory Investigation 2012; 92: 32-45Susztac K., Raff A.C., Schiffer M. et al. Glucose-induced reactive oxygen species cause apoptosis of podocytes and podocyte depletion at the onset of diabetic nephropathy. Diabetes 2006; 55: 226-233Susztac K., Raff A.C., Schiffer M. et al. Glucose-induced reactive oxygen species cause apoptosis of podocytes and podocyte depletion at the onset of diabetic nephropathy. Diabetes 2006; 55: 226-233Versola D., Gandolfo M.T., Ferrario.F et al. Apoptosis in the kidney of the patients with type 2 diabetic nephropathy. Intern Soc Nephrol. 2007; 72: 1262-1272.Versola D., Gandolfo M.T., Ferrario.F et al. Apoptosis in the kidney of the patients with type 2 diabetic nephropathy. Intern Soc Nephrol. 2007; 72: 1262-1272.Liu Y. New insights into epithelial-mesenchymal transitition contribute in kidney fibrosis. J Am Soc Nephrol 2010; 21: 212-222Liu Y. New insights into epithelial-mesenchymal transitition contribute in kidney fibrosis. J Am Soc Nephrol 2010; 21: 212-222Wolf G., Wenzel U., Ziadeh F.N. et al. Angiotensin convertingenzyme inhibitor treatment reduces glomerular p16 INK4 and p27Kip1 expression in diabetic BBdp rats. Diabetologia 1999; 42: 11425-11432Wolf G., Wenzel U., Ziadeh F.N. et al. Angiotensin convertingenzyme inhibitor treatment reduces glomerular p16 INK4 and p27Kip1 expression in diabetic BBdp rats. Diabetologia 1999; 42: 11425-11432Griffin S.V., Peterman A.N., Durvasula R.V. et al. Podocyte proliferation and differentiation in glomerular disease: role of cell-cycle regulatory proteins. Nephrol Dial Transplant 2003; 18(6): 8-13Griffin S.V., Peterman A.N., Durvasula R.V. et al. Podocyte proliferation and differentiation in glomerular disease: role of cell-cycle regulatory proteins. Nephrol Dial Transplant 2003; 18(6): 8-13Xu Z.G.,Yoo T.H., Ryu D.R. et al. Angiotensin II receptor blocker inhibits p27Kip1 expression in glucose stimulated podocytes and in diabetic glomeruli. Kidney Intern 2005; 67: 944-952Xu Z.G.,Yoo T.H., Ryu D.R. et al. Angiotensin II receptor blocker inhibits p27Kip1 expression in glucose stimulated podocytes and in diabetic glomeruli. Kidney Intern 2005; 67: 944-952Hoshi S., Shu Y. Yoshida F et al. Podocyte injury promotes progressive nephropathy in Zucker diabetic fatty rats. Lab Invest 2002; 82: 25-35Hoshi S., Shu Y. Yoshida F et al. Podocyte injury promotes progressive nephropathy in Zucker diabetic fatty rats. Lab Invest 2002; 82: 25-35Kriz W., Le Hir M. Pathway to nephron loss starting from glomerular diseases-insights from animal models. Kidney Intern 2005; 67: 404-419Kriz W., Le Hir M. Pathway to nephron loss starting from glomerular diseases-insights from animal models. Kidney Intern 2005; 67: 404-419Wiggins R.C.: The spectrum of podocytopathies: A unifying view of glomerular diseases. Kidney Int 2007; 71: 1205-1214Wiggins R.C.: The spectrum of podocytopathies: A unifying view of glomerular diseases. Kidney Int 2007; 71: 1205-1214Steffes M.W., Schmidt D., Mc Grery R. et al. Glomerular cell number in normal subjects and in type 1diabetic patients. Kidney Intern 2001; 59: 2104-2113Steffes M.W., Schmidt D., Mc Grery R. et al. Glomerular cell number in normal subjects and in type 1diabetic patients. Kidney Intern 2001; 59: 2104-2113Meyer T.W., Bennett P.H., Nelson R.G. et al. Podocyte number predicts long-term urinary albumin excretion in Pima Indians with type II diabetes and microalbuminuria. Diabetologia 1999; 42: 1341-1344Meyer T.W., Bennett P.H., Nelson R.G. et al. Podocyte number predicts long-term urinary albumin excretion in Pima Indians with type II diabetes and microalbuminuria. Diabetologia 1999; 42: 1341-1344White K.E., Bilous R.W. Structural alterations to the podocyte are related to proteinuria in 2 type diabetic patients. Nephrol Dial Transplant 2004; 9: 1437-1440White K.E., Bilous R.W. Structural alterations to the podocyte are related to proteinuria in 2 type diabetic patients. Nephrol Dial Transplant 2004; 9: 1437-1440Abbate M., Zoja C., Morigi M. et al. Transforming growth factor-beta 1 is upregulated by podocytes in response to excess intraglomerular passage of proteins: a central pathway in progressive glomerulosclerosis. Am J Pathol 2002; 161: 21792193Abbate M., Zoja C., Morigi M. et al. Transforming growth factor-beta 1 is upregulated by podocytes in response to excess intraglomerular passage of proteins: a central pathway in progressive glomerulosclerosis. Am J Pathol 2002; 161: 21792193Durvasula R.V., Petermann A.T., Hiromura K. et al. Activation of local tissue angiotensin system in podocytes by mechanical strain. Kidney Intern 2004; 65: 309Durvasula R.V., Petermann A.T., Hiromura K. et al. Activation of local tissue angiotensin system in podocytes by mechanical strain. Kidney Intern 2004; 65: 309Ichihara A., Kaneshiro Y. Takemuro T. et al. The (pro)renin receptor and the kidney. Sem Nephrol 2007; 27: 524-528Ichihara A., Kaneshiro Y. Takemuro T. et al. The (pro)renin receptor and the kidney. Sem Nephrol 2007; 27: 524-528Parving H.H., Persson P., Lewis E.J. et al. Aliskiren combined with losartan in type 2 diabetes and nephropathy. N Eng J Med 2008; 358: 2433-2446Parving H.H., Persson P., Lewis E.J. et al. Aliskiren combined with losartan in type 2 diabetes and nephropathy. N Eng J Med 2008; 358: 2433-2446Ding G., Reddy K., Kapasi A.A. et al. Angiotensin II induces apoptosis in rat glomerularepithelial cells. Am J Physiol Renal Physio. 2002; 283: F173-180Ding G., Reddy K., Kapasi A.A. et al. Angiotensin II induces apoptosis in rat glomerularepithelial cells. Am J Physiol Renal Physio. 2002; 283: F173-180Schiffer M., Mundel P., Shaw A.S. et al. A novel role for the adapter molecule CD2-associated protein in transforming growth factor-beta-1-induced apoptosis. J Biol Chem 2004; 279: 3700437012Schiffer M., Mundel P., Shaw A.S. et al. A novel role for the adapter molecule CD2-associated protein in transforming growth factor-beta-1-induced apoptosis. J Biol Chem 2004; 279: 3700437012Mifsud S.A., Allen T.J., Bertram J.F. et al. Podocyte foot process broadening in experimental diabetic nephropathy: amelioration with renin-angiotensin blockade. Diabetologia 2001; 44: 878-882Mifsud S.A., Allen T.J., Bertram J.F. et al. Podocyte foot process broadening in experimental diabetic nephropathy: amelioration with renin-angiotensin blockade. Diabetologia 2001; 44: 878-882Gross M.L., El-Shakmak A., Szabo A. et al. ACE-inhibitor but not endothelin receptor blockers prevent podocyte loss in early nephropathy. Diabetologia 2003; 46: 856-868Gross M.L., El-Shakmak A., Szabo A. et al. ACE-inhibitor but not endothelin receptor blockers prevent podocyte loss in early nephropathy. Diabetologia 2003; 46: 856-868Flannery P.J., Spurney R.F. Transactivation of epidermal growth factor receptor by angiotensin II in glomerular podocytes. Nephrol Exp Nephrol 2006; 103: e109-1018Flannery P.J., Spurney R.F. Transactivation of epidermal growth factor receptor by angiotensin II in glomerular podocytes. Nephrol Exp Nephrol 2006; 103: e109-1018Yard B.A., Kahlert S., Engelleiter R. et al. Decreased glomerular expression of agrin in diabetic nephropathy and podocytes, culturedin high dglucose medium. Exp Nephrol 2001; 9: 214-222Yard B.A., Kahlert S., Engelleiter R. et al. Decreased glomerular expression of agrin in diabetic nephropathy and podocytes, culturedin high dglucose medium. Exp Nephrol 2001; 9: 214-222Chen S., Lee J.S., Iglesias-de la Cruz M.C. et al. Angiotensin II stimulates alpha3(IV) collagen production in mouse podocytes via TGF-beta and VEGF signalling: implications for diabetic glomerulopathy. Nephrol Dial Transplant 2005; 20: 1320-1328Chen S., Lee J.S., Iglesias-de la Cruz M.C. et al. Angiotensin II stimulates alpha3(IV) collagen production in mouse podocytes via TGF-beta and VEGF signalling: implications for diabetic glomerulopathy. Nephrol Dial Transplant 2005; 20: 1320-1328Wolf G. Free radical production and angiotensin. Curr Hypertens Rep. 2000; 2: 167-173.Wolf G. Free radical production and angiotensin. Curr Hypertens Rep. 2000; 2: 167-173.Kritz W., LeHir M. Pathways to nephron loss starting from glomerular diseases-insights from animal models. Kidney Intern 2005; 67: 404-419Kritz W., LeHir M. Pathways to nephron loss starting from glomerular diseases-insights from animal models. Kidney Intern 2005; 67: 404-419Böttinger E.P. TGF-beta in renal injury and disease. Semin Nephrol 2007; 27(3): 309-320Böttinger E.P. TGF-beta in renal injury and disease. Semin Nephrol 2007; 27(3): 309-320Chen S., Jim B., Ziyadeh F.N. Diabetic nephropathy and transforming growth factor-beta: transforming our view of glomerulosclerosis and fibrosis buildup. Sem Nephrol 2003; 23: 532-543Chen S., Jim B., Ziyadeh F.N. Diabetic nephropathy and transforming growth factor-beta: transforming our view of glomerulosclerosis and fibrosis buildup. Sem Nephrol 2003; 23: 532-543Leask A., Abraham D.J. TGF-ß signaling and the fibrotic response. FASEB Journal 2004; 18 (7): 816-827Leask A., Abraham D.J. TGF-ß signaling and the fibrotic response. FASEB Journal 2004; 18 (7): 816-827Li Y., Kang Y.S., Dai C. et al. Epithelial-to-mesenchymal transition is a potential pathway leading to podocyte dysfunction and proteinuria. Am J Pathol 2008; 172: 299-308Li Y., Kang Y.S., Dai C. et al. Epithelial-to-mesenchymal transition is a potential pathway leading to podocyte dysfunction and proteinuria. Am J Pathol 2008; 172: 299-308Yamaguchi Y., Iwano M., Suzuki D. et al. Epithelial-mesenchymal transition as a potential explanation for podocyte depletion in diabetic nephropathy. Am J Kidney Dis 2009; 54(4): 653-664Yamaguchi Y., Iwano M., Suzuki D. et al. Epithelial-mesenchymal transition as a potential explanation for podocyte depletion in diabetic nephropathy. Am J Kidney Dis 2009; 54(4): 653-664Tufro А. VEGF and podocytes in diabetic nephropathy. Sem Nephrol 2012; 32 (4): 385-393Tufro А. VEGF and podocytes in diabetic nephropathy. Sem Nephrol 2012; 32 (4): 385-393Veron D., Bertuccio C.A., Marlier A. et al. Podocyte vascular endothelial growth factor (Vegf164) overexpression causes severe nodular glomerulosclerosis in a mouse model of type 1 diabetes. Diabetologia 2011; 54: 1227-1241Veron D., Bertuccio C.A., Marlier A. et al. Podocyte vascular endothelial growth factor (Vegf164) overexpression causes severe nodular glomerulosclerosis in a mouse model of type 1 diabetes. Diabetologia 2011; 54: 1227-1241Kim N.H., Kim K.B., Kim D.L. et al. Plasma and urinary vascular endothelial growth factor and diabetic nephropathy in type 2 diabetes mellitus. Diabet Med 2004; 21: 545-551Kim N.H., Kim K.B., Kim D.L. et al. Plasma and urinary vascular endothelial growth factor and diabetic nephropathy in type 2 diabetes mellitus. Diabet Med 2004; 21: 545-551Fan Q., Xing Y., Ding J., Guan N. Reduction in VEGF protein and phosphorylated nephrin associated with proteinuria in adria-mycin nephropathy rats. Nephron Exp Nephrol 2009; 111: e92Fan Q., Xing Y., Ding J., Guan N. Reduction in VEGF protein and phosphorylated nephrin associated with proteinuria in adria-mycin nephropathy rats. Nephron Exp Nephrol 2009; 111: e92Foster R.R., Saleem M.A., Mathieson P.W. et al. Vascular endothelial growth factor and nephrin interact and reduce apoptosis in human podocyte. Am J Physiol Renal Physiol 2005; 288: F48-57Foster R.R., Saleem M.A., Mathieson P.W. et al. Vascular endothelial growth factor and nephrin interact and reduce apoptosis in human podocyte. Am J Physiol Renal Physiol 2005; 288: F48-57Nakamura T., Ushiyama C., Osada S. et al. Pioglitazone reduces urinary podocyte excretion in type 2 diabetes patients with microalbuminuria. Metabolism 2001; 50: 1193-1196Nakamura T., Ushiyama C., Osada S. et al. Pioglitazone reduces urinary podocyte excretion in type 2 diabetes patients with microalbuminuria. Metabolism 2001; 50: 1193-1196Zhang Y., Guan Y. PPAR-gamma agonists and diabetic nephropathy. Curr Diab Rep 2005; 5: 470-475Zhang Y., Guan Y. PPAR-gamma agonists and diabetic nephropathy. Curr Diab Rep 2005; 5: 470-475Benigni A., Zoja C., Tomasoni S. et al. Transcriptional regulation of nephrin gene by peroxisome proliferator-activated receptor-γ agonist: molecular mechanism of the antiproteinuric effect of pioglitazone. J Am Soc Nephrol 2006; 17: 1624-1632Benigni A., Zoja C., Tomasoni S. et al. Transcriptional regulation of nephrin gene by peroxisome proliferator-activated receptor-γ agonist: molecular mechanism of the antiproteinuric effect of pioglitazone. J Am Soc Nephrol 2006; 17: 1624-1632Lennon R., Welsh G.I., Singh A. Rosiglitazone enhances glucose uptake in glomerular podocytes using the glucose transporter GLUT1. Diabetologia 2009; 52: 1944-1952Lennon R., Welsh G.I., Singh A. Rosiglitazone enhances glucose uptake in glomerular podocytes using the glucose transporter GLUT1. Diabetologia 2009; 52: 1944-1952Zhang H., Saha J., Byun J. et al. Rosiglitazone reduces renal and plasma markers of oxidative injury and reverses urinary metabolite abnormalities in the amelioration of diabetic nephropathy. Am J Physiol Renal Physiol 2008; 295: F1071-F1081Zhang H., Saha J., Byun J. et al. Rosiglitazone reduces renal and plasma markers of oxidative injury and reverses urinary metabolite abnormalities in the amelioration of diabetic nephropathy. Am J Physiol Renal Physiol 2008; 295: F1071-F1081Крячкова А.А., Савельева С.А., Галлямов М.Г. и др. Роль ожирения в поражении почек при метаболическом синдроме. Нефрология и диализ 2010 12(1): 34-38 [Kriachkova A.A., Savel'eva S.A., Galliamov M.G. i dr. Rol' ozhireniia v porazhenii pochek pri metabolicheskom sindrome. Nefrologiia i dializ 2010 12(1): 34-38]Крячкова А.А., Савельева С.А., Галлямов М.Г. и др. Роль ожирения в поражении почек при метаболическом синдроме. Нефрология и диализ 2010 12(1): 34-38 [Kriachkova A.A., Savel'eva S.A., Galliamov M.G. i dr. Rol' ozhireniia v porazhenii pochek pri metabolicheskom sindrome. Nefrologiia i dializ 2010 12(1): 34-38]Савельева С.А., Крячкова А.А., Курумова К.О. и др. Ожирение - фактор риска поражения почек у больных сахарным диабетом 2 типа. Сахарный диабет 2010; 2: 45-50 [ Savel'eva S.A., Kriachkova A.A., Kurumova K.O. i dr. Ozhirenie - faktor riska porazheniia pochek u bol'ny'kh saharny'm diabetom 2 tipa. Saharny'i' diabet 2010; 2: 45-50]Савельева С.А., Крячкова А.А., Курумова К.О. и др. Ожирение - фактор риска поражения почек у больных сахарным диабетом 2 типа. Сахарный диабет 2010; 2: 45-50 [ Savel'eva S.A., Kriachkova A.A., Kurumova K.O. i dr. Ozhirenie - faktor riska porazheniia pochek u bol'ny'kh saharny'm diabetom 2 tipa. Saharny'i' diabet 2010; 2: 45-50]Сагинова Е.А., Северова М.М., Галлямов М.Г. и др. Клиническое значение адипонектинемии в формировании поражения органов-мишеней при метаболическом синдроме, ассоциированном с неалкогольной жировой болезнью печени. Сеченовский вестн 2011; 1-3: 18-25 [Saginova E.A., Severova M.M., Galliamov M.G. i dr. Clinicheskoe znachenie adiponektinemii v formirovanii porazheniia organov-mishenei' pri metabolicheskom sindrome, assotciirovannom s nealkogol'noi' zhirovoi' bolezn'iu pecheni. Sechenovskii' vestneyk 2011; 1-3: 18-25]Сагинова Е.А., Северова М.М., Галлямов М.Г. и др. Клиническое значение адипонектинемии в формировании поражения органов-мишеней при метаболическом синдроме, ассоциированном с неалкогольной жировой болезнью печени. Сеченовский вестн 2011; 1-3: 18-25 [Saginova E.A., Severova M.M., Galliamov M.G. i dr. Clinicheskoe znachenie adiponektinemii v formirovanii porazheniia organov-mishenei' pri metabolicheskom sindrome, assotciirovannom s nealkogol'noi' zhirovoi' bolezn'iu pecheni. Sechenovskii' vestneyk 2011; 1-3: 18-25]Sharma K., Ramachandrarao S., Qiu G. et al. Adiponectin regulates albuminuria and podocyte function in mice. J Clin Invest 2008; 118: 1645-1656Sharma K., Ramachandrarao S., Qiu G. et al. Adiponectin regulates albuminuria and podocyte function in mice. J Clin Invest 2008; 118: 1645-1656Lee M.H., Song H.K., Ko G.J. et al. Angiotensin receptor blockers improve insulin resistance in type 2 diabetic rats by modulating adipose tissue. Kidney Int 2008; 74: 890-900Lee M.H., Song H.K., Ko G.J. et al. Angiotensin receptor blockers improve insulin resistance in type 2 diabetic rats by modulating adipose tissue. Kidney Int 2008; 74: 890-900Lenz O., Fornoni A. Renin-angiotensin system blockade and diabetes: moving the adipose organ from the periphery to the center. Kidney Int 2008; 74: 851-853Lenz O., Fornoni A. Renin-angiotensin system blockade and diabetes: moving the adipose organ from the periphery to the center. Kidney Int 2008; 74: 851-853Harvey S.J., Jarad G., Cunningham J. et al. Podocyte-specific deletion of dicer alters cytoskeletal dynamics and causes glomerular disease. J Am Soc Nephrol 2008; 19: 2150-2158Harvey S.J., Jarad G., Cunningham J. et al. Podocyte-specific deletion of dicer alters cytoskeletal dynamics and causes glomerular disease. J Am Soc Nephrol 2008; 19: 2150-2158Ho J., Ng K.H., Rosen S. et al. Podocyte-specific loss of functional microRNAs leads to rapid glomerular and tubular injury. J Am Soc Nephrol 2008; 19: 2069-2065Ho J., Ng K.H., Rosen S. et al. Podocyte-specific loss of functional microRNAs leads to rapid glomerular and tubular injury. J Am Soc Nephrol 2008; 19: 2069-2065Kato M., Zhang J., Wang M. et al. MicroRNA-192 in diabetic kidney glomeruli and its function in TGF-beta-induced collagen expression via inhibition of E-box repressors. Proc Nat Acad Sci USA 2007; 104: 3432-3437Kato M., Zhang J., Wang M. et al. MicroRNA-192 in diabetic kidney glomeruli and its function in TGF-beta-induced collagen expression via inhibition of E-box repressors. Proc Nat Acad Sci USA 2007; 104: 3432-3437

The authors declare that there are no conflicts of interest present.