medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2017-3-8-16medsovet-1742Research ArticleСАХАРНЫЙ ДИАБЕТDIABETES MELLITUSПЕРСПЕКТИВЫ НЕФРОПРОТЕКЦИИ ПРИ САХАРНОМ ДИАБЕТЕ 2-го ТИПА C ИСПОЛЬЗОВАНИЕМ ИНГИБИТОРА ДПП-4 ВИЛДАГЛИПТИНАPROSPECTS OF NEPHROPROTECTION AGAINST TYPE 2 DIABETES USING THE DPP-4 INHIBITOR VILDAGLIPTINБайрашеваВ. К.BayrashevaV. K.

Санкт-Петербург

Saint-Petersburg

БабенкоА. Ю.BabenkoA. Y.

д.м.н., 

Санкт-Петербург

MD, 

Saint-Petersburg

БайрамовА. А.BayramovA. A.

д.м.н., 

Санкт-Петербург

MD, 

Saint-Petersburg

ЧефуС. Г.ChefuS. G.

к.б.н., 

Санкт-Петербург

PhD in biology, 

Saint-Petersburg

ШаталовИ. С.ShatalovI. S.

Санкт-Петербург

Saint-Petersburg

ПчелинИ. Ю.PchelinI. Y.

к.м.н., 

Санкт-Петербург

PhD in medicine, 

Saint-Petersburg

АрефьеваА. Н.ArefievaA. N.

Санкт-Петербург

Saint-Petersburg

ГриневаЕ. Н.GrinevaE. N.

д.м.н., профессор,

Санкт-Петербург

MD, Prof.,

Saint-Petersburg

Северо-Западный федеральный медицинский исследовательский центр им. В.А. Алмазова Минздрава России, Институт эндокринологии; Первый Санкт-Петербургский государственный медицинский университет им. И.П. Павлова Минздрава РоссииРоссияAlmazov Federal North-West Medical Research Centre of the Ministry of Health of Russia, Institute of Endocrinology; Pavlov First Saint-Petersburg State Medical University of the Ministry of Health of RussiaRussian FederationСеверо-Западный федеральный медицинский исследовательский центр им. В.А. Алмазова Минздрава России, Институт эндокринологииРоссияAlmazov Federal North-West Medical Research Centre of the Ministry of Health of Russia, Institute of EndocrinologyRussian FederationПервый Санкт-Петербургский государственный медицинский университет им. И.П. Павлова Минздрава РоссииРоссияPavlov First Saint-Petersburg State Medical University of the Ministry of Health of RussiaRussian FederationСанкт-Петербургский национальный исследовательский университет информационных технологий, механики и оптикиРоссияSt.-Petersburg National Research University of Information Technologies, Mechanics and OpticsRussian FederationСанкт-Петербургский государственный университетРоссияSaint-Petersburg State UniversityRussian Federation20173012201703816Copyright © Байрашева В.К., Бабенко А.Ю., Байрамов А.А., Чефу С.Г., Шаталов И.С., Пчелин И.Ю., Арефьева А.Н., Гринева Е.Н., 20172017Байрашева В.К., Бабенко А.Ю., Байрамов А.А., Чефу С.Г., Шаталов И.С., Пчелин И.Ю., Арефьева А.Н., Гринева Е.Н.Bayrasheva V.K., Babenko A.Y., Bayramov A.A., Chefu S.G., Shatalov I.S., Pchelin I.Y., Arefieva A.N., Grineva E.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/1742

Диабетическая нефропатия (ДН) является грозным осложнением сахарного диабета (СД), повышающим инвалидизацию и смертность. Накоплены данные, в основном экспериментальные, что ингибиторы ДПП-4 обладают негликемическими тканевыми эффектами, включая нефропротективные. Клинических данных, подтверждающих эти эффекты, недостаточно. Это делает актуальным изучение влияния иДПП-4 на почечную функцию у пациентов с СД 2-го типа.

С целью изучения эффектов иДПП-4 вилдаглиптина на гликемические, метаболические и почечные параметры у пациентов с СД 2-го типа с ХБП 1–2, получающих инсулинотерапию, обследовано 44 пациента, рандомизированных продолжить терапию инсулином или получать дополнительно к инсулину вилдаглиптин в дозе 50 мг/сут, с оценкой результатов через 6 месяцев. В группе терапии вилдаглиптином произошло достоверное снижение HbA1c, постпрандиальной гликемии, диастолического АД, индекса HOMA-IR, потребности в инсулине и снижение частоты гипогликемий. Также в этой группе отмечалась положительная динамика показателей гломерулярной функции почки – значимое уменьшение альбуминурии, а также достоверное повышение рСКФ по цистатину С и снижение экскреции коллагена IV типа. Полученные данные свидетельствуют как о ранее подтвержденном в клинических исследованиях положительном влиянии вилдаглиптина на метаболический статус, показатели гликемии и гемодинамики, так и о независимой от гликемических эффектов способности вилдаглиптина тормозить развитие гломерулярной дисфункции у пациентов с СД 2-го типа и начальными проявлениями ДН.

Diabetic nephropathy (DN) is a serious complication of diabetes mellitus (DM), which increases morbidity and mortality. Accumulated evidence, mostly experimental ones that DPP-4 inhibitors have non-glycemic tissue effects including renal protection. Clinical data confirming these effects are insufficient. This makes it relevant to study the influence of iDPP-4 on the renal function in patients with Type 2 diabetes.

To study the effects of iDPP vildagliptin on glycemic, metabolic and renal parameters in patients with type 2 diabetes with CKD 1–2 receiving insulin therapy 44 patients were randomized to continue therapy with insulin or insulin + vildagliptin at a dose of 50 mg/day, with the evaluation of results in 6 months.

In group of vildagliptin therapy a significant decrease of HbA1c, postprandial glycemia, diastolic blood pressure, HOMA-IR, insulin demand and a reduction in the frequency of hypoglycemia occurred. The positive dynamics of indicators of glomerular functions of the kidney were noted in this group - a significant reduction in albuminuria and a significant increase in eGFR by cystatin C and decreased urinary excretion of type IV collagen. The findings suggest the positive effect of vildagliptin on metabolic status and indicators of glycaemia and hemodynamics as earlier confirmed in clinical studies and the ability of vildagliptin independent from glycemic effects to slow the development of glomerular dysfunction in patients with type 2 diabetes and the initial manifestations of DN. 

вилдаглиптиннефропротекциядиабетическая нефропатияэкскреция коллагена IV типаСКФ по цистатину Сvildagliptinnephroprotectiondiabetic nephropathyurinary excretion of type IV collagenEGFR by cystatin SReferencesДедов И.И., Шестакова М.В. (ред.) Алгоритмы специализированной медицинской помощи больным сахарным диабетом. 7-й выпуск. Сахарный диабет, 2015, 18(1S): 1-112.Дедов И.И., Шестакова М.В. (ред.) Алгоритмы специализированной медицинской помощи больным сахарным диабетом. 7-й выпуск. Сахарный диабет, 2015, 18(1S): 1-112.Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M et al. Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care, 2015, 38(1): 140-149.Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M et al. Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care, 2015, 38(1): 140-149.Mearns ES, Sobieraj DM, White CM, Saulsberry WJ, Kohn CG, Doleh Y, et al. Comparative efficacy and safety of antidiabetic drug regimens added to metformin monotherapy in patients with type 2 diabetes: a network meta-analysis. PLoS One, 2015, 10(4): e0125879.Mearns ES, Sobieraj DM, White CM, Saulsberry WJ, Kohn CG, Doleh Y, et al. Comparative efficacy and safety of antidiabetic drug regimens added to metformin monotherapy in patients with type 2 diabetes: a network meta-analysis. PLoS One, 2015, 10(4): e0125879.Шестакова М.В., Дедов И.И. Сахарный диабет и хроническая болезнь почек. М.: Медицинское информационное агенство; 2009. 482 с.Шестакова М.В., Дедов И.И. Сахарный диабет и хроническая болезнь почек. М.: Медицинское информационное агенство; 2009. 482 с.Pozzilli P, Leslie RD, Chan J, De Fronzo R, Monnier L, Raz I, et al. The A1C and ABCD of glycaemia management in type 2 diabetes: a physician’s personalized approach. Diabetes Metab Res Rev, 2010, 26(4): 239-244.Pozzilli P, Leslie RD, Chan J, De Fronzo R, Monnier L, Raz I, et al. The A1C and ABCD of glycaemia management in type 2 diabetes: a physician’s personalized approach. Diabetes Metab Res Rev, 2010, 26(4): 239-244.Бабенко А.Ю., Байрашева В.К. Диабетическая нефропатия: зависит ли ренопротекция от выбора сахароснижающей терапии? Медицинский совет, 2015, 7: 32-43.Бабенко А.Ю., Байрашева В.К. Диабетическая нефропатия: зависит ли ренопротекция от выбора сахароснижающей терапии? Медицинский совет, 2015, 7: 32-43.Шестакова М.В. Сахарный диабет и хроническая болезнь почек: возможности прогнозирования, ранней диагностики и нефропротекции в XXI веке. Терапевтический архив, 2016, 88(6): 84-88.Шестакова М.В. Сахарный диабет и хроническая болезнь почек: возможности прогнозирования, ранней диагностики и нефропротекции в XXI веке. Терапевтический архив, 2016, 88(6): 84-88.Ahrén B, Landin-Olsson M, Jansson PA, Svensson M, Holmes D, Schweizer A. Inhibition of dipeptidyl peptidase-4 reduces glycemia, sustains insulin levels, and reduces glucagon levels in type 2 diabetes. J Clin Endocrinol Metab, 2004, 89(5): 2078-2084.Ahrén B, Landin-Olsson M, Jansson PA, Svensson M, Holmes D, Schweizer A. Inhibition of dipeptidyl peptidase-4 reduces glycemia, sustains insulin levels, and reduces glucagon levels in type 2 diabetes. J Clin Endocrinol Metab, 2004, 89(5): 2078-2084.Mentlein R, Gallwitz B, Schmidt WE. Dipeptidylpeptidase IV hydrolyses gastric inhibitory polypeptide, glucagon-like peptide-1(7-36)amide, peptide histidine methionine and is responsiblefor their degradation in human serum. Eur J Biochem, 1993, 214: 829–835.Mentlein R, Gallwitz B, Schmidt WE. Dipeptidylpeptidase IV hydrolyses gastric inhibitory polypeptide, glucagon-like peptide-1(7-36)amide, peptide histidine methionine and is responsiblefor their degradation in human serum. Eur J Biochem, 1993, 214: 829–835.Gupta V. Pleiotropic effects of incretins. Indian J Endocrinol Metab, 2012, 6(Supp1l1): S47–S56.Gupta V. Pleiotropic effects of incretins. Indian J Endocrinol Metab, 2012, 6(Supp1l1): S47–S56.Chen C, Yu Q, Zhang S, Yang P, Wang CY. Assessing the efficacy and safety of combined DPP-4 inhibitor and insulin treatment in patients with type 2 diabetes: a meta-analysis. Int J Clin Exp Pathol, 2015, 8(11): 14141-14150.Chen C, Yu Q, Zhang S, Yang P, Wang CY. Assessing the efficacy and safety of combined DPP-4 inhibitor and insulin treatment in patients with type 2 diabetes: a meta-analysis. Int J Clin Exp Pathol, 2015, 8(11): 14141-14150.Аметов А.С., Карпова Е.В. Эффективность терапии ингибиторами ДПП-4 в комбинации с базальным инсулином у больных сахарным диабетом 2 типа. Сахарный диабет, 2011, 4: 55-59.Аметов А.С., Карпова Е.В. Эффективность терапии ингибиторами ДПП-4 в комбинации с базальным инсулином у больных сахарным диабетом 2 типа. Сахарный диабет, 2011, 4: 55-59.Cai L, Cai Y, Lu ZJ, Zhang Y, Liu P. The efficacy and safety of vildagliptin in patients with type 2 diabetes: a meta-analysis of randomized clinical trials. J Clin Pharm Ther, 2012, 37(4): 386-398.Cai L, Cai Y, Lu ZJ, Zhang Y, Liu P. The efficacy and safety of vildagliptin in patients with type 2 diabetes: a meta-analysis of randomized clinical trials. J Clin Pharm Ther, 2012, 37(4): 386-398.Mannucci E, Mosenzon O, Avogaro A. Analyses of results from cardiovascular safety trials with DPP-4 inhibitors: cardiovascular outcomes, predefined safety outcomes, and pooled analysis and metaanalysis. Diabetes Care, 2016, 39(Suppl 2): 196-204.Mannucci E, Mosenzon O, Avogaro A. Analyses of results from cardiovascular safety trials with DPP-4 inhibitors: cardiovascular outcomes, predefined safety outcomes, and pooled analysis and metaanalysis. Diabetes Care, 2016, 39(Suppl 2): 196-204.Kim NH, Yu T, Lee DH. The nonglycemic actions of dipeptidyl peptidase-4 inhibitors. Biomed Res Int, 2014, 2014: 368703.Kim NH, Yu T, Lee DH. The nonglycemic actions of dipeptidyl peptidase-4 inhibitors. Biomed Res Int, 2014, 2014: 368703.Aroor AR, Sowers JR, Jia G, DeMarco VG. Pleiotropic effects of the dipeptidylpeptidase-4 inhibitors on the cardiovascular system. Am J Physiol Heart Circ Physiol, 2014, 307(4): H477-492.Aroor AR, Sowers JR, Jia G, DeMarco VG. Pleiotropic effects of the dipeptidylpeptidase-4 inhibitors on the cardiovascular system. Am J Physiol Heart Circ Physiol, 2014, 307(4): H477-492.Pyke C, Heller RS, Kirk RK, Ørskov C, ReedtzRunge S, Kaastrup P, et al. GLP-1 receptor localization in monkey and human tissue: novel distribution revealed with extensively validated monoclonal antibody. Endocrinology, 2014, 155(4): 1280-1290.Pyke C, Heller RS, Kirk RK, Ørskov C, ReedtzRunge S, Kaastrup P, et al. GLP-1 receptor localization in monkey and human tissue: novel distribution revealed with extensively validated monoclonal antibody. Endocrinology, 2014, 155(4): 1280-1290.Körner M, Stöckli M, Waser B, Reubi JC. GLP-1 receptor expression in human tumors and human normal tissues: potential for in vivo targeting. J Nucl Med, 2007, 48(5): 736-743.Körner M, Stöckli M, Waser B, Reubi JC. GLP-1 receptor expression in human tumors and human normal tissues: potential for in vivo targeting. J Nucl Med, 2007, 48(5): 736-743.Panchapakesan U, Pollock C. The role of dipeptidyl peptidase - 4 inhibitors in diabetic kidney disease. Front Immunol, 2015, 6: 443.Panchapakesan U, Pollock C. The role of dipeptidyl peptidase - 4 inhibitors in diabetic kidney disease. Front Immunol, 2015, 6: 443.Корбут А. И., Климонтов В. В. Терапия, основанная на инкретинах: почечные эффекты. Сахарный диабет, 2016, 19(1): 53-63.Корбут А. И., Климонтов В. В. Терапия, основанная на инкретинах: почечные эффекты. Сахарный диабет, 2016, 19(1): 53-63.Juillerat-Jeanneret L. Dipeptidyl peptidase IV and its inhibitors: therapeutics for type 2 diabetes and what else? J Med Chem, 2014, 57(6): 2197-2212.Juillerat-Jeanneret L. Dipeptidyl peptidase IV and its inhibitors: therapeutics for type 2 diabetes and what else? J Med Chem, 2014, 57(6): 2197-2212.Dipeptidyl Aminopeptidases. Basic Science and Clinical Applications. In: U Lendeckel, D Reinhold, U Bank, editors. Advanced in experimental medicine and biology. 1st ed. USA: Springer US, 2006. Vol 575: 3-38.Dipeptidyl Aminopeptidases. Basic Science and Clinical Applications. In: U Lendeckel, D Reinhold, U Bank, editors. Advanced in experimental medicine and biology. 1st ed. USA: Springer US, 2006. Vol 575: 3-38.Mamgain S, Mathur S, Kothiyal P. Immunomodu latory activity of DPP4. J Pharmacol Clin Toxicol, 2013, 1(1): 1006.Mamgain S, Mathur S, Kothiyal P. Immunomodu latory activity of DPP4. J Pharmacol Clin Toxicol, 2013, 1(1): 1006.Mentlein R, Gallwitz B, Schmidt WE. Ohnuma K, Takahashi N, Yamochi T, Hosono O, Dang NH, Morimoto C. Role of CD26/dipeptidyl peptidase IV in human T cell activation and function. Front Biosci, 2008, 13: 2299-2310.Mentlein R, Gallwitz B, Schmidt WE. Ohnuma K, Takahashi N, Yamochi T, Hosono O, Dang NH, Morimoto C. Role of CD26/dipeptidyl peptidase IV in human T cell activation and function. Front Biosci, 2008, 13: 2299-2310.Pala L, Mannucci E, Pezzatini A, Ciani S, Sardi J, Raimondi L, et al. Dipeptidyl peptidase-IV expression and activity in human glomerular endothelial cells. Biochem Biophys Res Commun, 2003, 310(1): 28-31.Pala L, Mannucci E, Pezzatini A, Ciani S, Sardi J, Raimondi L, et al. Dipeptidyl peptidase-IV expression and activity in human glomerular endothelial cells. Biochem Biophys Res Commun, 2003, 310(1): 28-31.Helbert MJ, Dauwe SE, Van der Biest I, Nouwen EJ, De Broe ME. Immunodissection of the human proximal nephron: flow sorting of S1S2S3, S1S2 and S3 proximal tubular cells. Kidney Int, 1997, 52(2): 414-428.Helbert MJ, Dauwe SE, Van der Biest I, Nouwen EJ, De Broe ME. Immunodissection of the human proximal nephron: flow sorting of S1S2S3, S1S2 and S3 proximal tubular cells. Kidney Int, 1997, 52(2): 414-428.Байрашева В.К., Бабенко А.Ю., Дмитриев Ю.В., Иванова А.Н., Шаталов И.С., Гринева Е.Н. Нефропротективные свойства ингибитора ДПП-4 в условиях экспериментальной диабетической нефропатии. Современные проблемы науки и образования, 2015, 3: 247(8). www.science-education.ru/123-20212.Байрашева В.К., Бабенко А.Ю., Дмитриев Ю.В., Иванова А.Н., Шаталов И.С., Гринева Е.Н. Нефропротективные свойства ингибитора ДПП-4 в условиях экспериментальной диабетической нефропатии. Современные проблемы науки и образования, 2015, 3: 247(8). www.science-education.ru/123-20212.Байрашева В.К., Бабенко А.Ю., Чефу С.Г., Дмитриев Ю.В., Шаталов И.С., Гринева Е.Н. Ингибиторы ДПП-4: от сахароснижающего эффекта до нефропротекции. Балтийский журнал современной эндокринологии, 2015, 11: 23-26.Байрашева В.К., Бабенко А.Ю., Чефу С.Г., Дмитриев Ю.В., Шаталов И.С., Гринева Е.Н. Ингибиторы ДПП-4: от сахароснижающего эффекта до нефропротекции. Балтийский журнал современной эндокринологии, 2015, 11: 23-26.Nistala R, Habibi J, Aroor A, Sowers JR, Hayden MR, Meuth A, et al. DPP4 inhibition attenuates filtration barrier injury and oxidant stress in the zucker obese rat. Obesity (Silver Spring), 2014, 22(10): 2172-2179.Nistala R, Habibi J, Aroor A, Sowers JR, Hayden MR, Meuth A, et al. DPP4 inhibition attenuates filtration barrier injury and oxidant stress in the zucker obese rat. Obesity (Silver Spring), 2014, 22(10): 2172-2179.Tanaka Y, Kume S, Chin-Kanasaki M, Araki H, Araki S, Ugi S, et al. Renoprotective effect of DPP-4 inhibitors against free fatty acid-bound albumininduced renal proximal tubular cell injury. Biochem Biophys Res Commun, 2016, 470(3): 539-545.Tanaka Y, Kume S, Chin-Kanasaki M, Araki H, Araki S, Ugi S, et al. Renoprotective effect of DPP-4 inhibitors against free fatty acid-bound albumininduced renal proximal tubular cell injury. Biochem Biophys Res Commun, 2016, 470(3): 539-545.Gangadharan Komala M, Gross S, Zaky A, Pollock C, Panchapakesan U. Saxagliptin reduces renal tubulointerstitial inflammation, hypertrophy and fibrosis in diabetes. Nephrology (Carlton), 2016, 21(5): 423-431.Gangadharan Komala M, Gross S, Zaky A, Pollock C, Panchapakesan U. Saxagliptin reduces renal tubulointerstitial inflammation, hypertrophy and fibrosis in diabetes. Nephrology (Carlton), 2016, 21(5): 423-431.Ali SM, Khalifa H, Mostafa DK, E Sharkawy A. Suppression of connective tissue growth factor mediates the renoprotective effect of Sitagliptin rather than Pioglitazone in type 2 diabetes mellitus. Life Sci, 2016, 153: 180-187.Ali SM, Khalifa H, Mostafa DK, E Sharkawy A. Suppression of connective tissue growth factor mediates the renoprotective effect of Sitagliptin rather than Pioglitazone in type 2 diabetes mellitus. Life Sci, 2016, 153: 180-187.Haluzík M, Frolík J, Rychlík I. Renal effects of DPP-4 inhibitors: a focus on microalbuminuria. Int J Endocrinol, 2013, 2013: 895102.Haluzík M, Frolík J, Rychlík I. Renal effects of DPP-4 inhibitors: a focus on microalbuminuria. Int J Endocrinol, 2013, 2013: 895102.Penno G, Garofolo M, Del Prato S. Dipeptidyl peptidase-4 inhibition in chronic kidney disease and potential for protection against diabetesrelated renal injury. Nutr Metab Cardiovasc Dis, 2016, 26(5): 361-373.Penno G, Garofolo M, Del Prato S. Dipeptidyl peptidase-4 inhibition in chronic kidney disease and potential for protection against diabetesrelated renal injury. Nutr Metab Cardiovasc Dis, 2016, 26(5): 361-373.Baetta R, Corsini A. Pharmacology of dipeptidyl peptidase-4 inhibitors: similarities and differences. Drugs, 2011, 71(11): 1441-1467.Baetta R, Corsini A. Pharmacology of dipeptidyl peptidase-4 inhibitors: similarities and differences. Drugs, 2011, 71(11): 1441-1467.Mulvihill EE, Drucker DJ. Pharmacology, physiology, and mechanisms of action of dipeptidyl peptidase-4 inhibitors. Endocr Rev, 2014, 35(6): 992-1019.Mulvihill EE, Drucker DJ. Pharmacology, physiology, and mechanisms of action of dipeptidyl peptidase-4 inhibitors. Endocr Rev, 2014, 35(6): 992-1019.Liu WJ, Xie SH, Liu YN, Kim W, Jin HY, Park SK, et al. Dipeptidyl peptidase IV inhibitor attenuates kidney injury in streptozotocin-induced diabetic rats. J Pharmacol Exp Ther, 2012, 340(2): 248-255.Liu WJ, Xie SH, Liu YN, Kim W, Jin HY, Park SK, et al. Dipeptidyl peptidase IV inhibitor attenuates kidney injury in streptozotocin-induced diabetic rats. J Pharmacol Exp Ther, 2012, 340(2): 248-255.Vavrinec P, Henning RH, Landheer SW, et al. Vildagliptin restores renal myogenic function and attenuates renal sclerosis independently of effects on blood glucose or proteinuria in zucker diabetic fatty rat. Curr Vasc Pharmacol, 2014, 12(6): 836-844.Vavrinec P, Henning RH, Landheer SW, et al. Vildagliptin restores renal myogenic function and attenuates renal sclerosis independently of effects on blood glucose or proteinuria in zucker diabetic fatty rat. Curr Vasc Pharmacol, 2014, 12(6): 836-844.Glorie LL, Verhulst A, Matheeussen V, Baerts L, Magielse J, Hermans N, et al. DPP4 inhibition improves functional outcome after renal ischemia-reperfusion injury. Am J Physiol Renal Physiol, 2012, 303(5): F681-688.Glorie LL, Verhulst A, Matheeussen V, Baerts L, Magielse J, Hermans N, et al. DPP4 inhibition improves functional outcome after renal ischemia-reperfusion injury. Am J Physiol Renal Physiol, 2012, 303(5): F681-688.Bekiari E, Rizava C, Athanasiadou E, Papatheodorou K, Liakos A, Karagiannis T, et al. Systematic review and meta-analysis of vildagliptin for treatment of type 2 diabetes. Endocrine, 2016, 52(3): 458-480.Bekiari E, Rizava C, Athanasiadou E, Papatheodorou K, Liakos A, Karagiannis T, et al. Systematic review and meta-analysis of vildagliptin for treatment of type 2 diabetes. Endocrine, 2016, 52(3): 458-480.Kothny W, Shao Q, Groop PH, Lukashevich V. One-year safety, tolerability and efficacy of vildagliptin in patients with type 2 diabetes and moderate or severe renal impairment. Diabetes Obes Metab, 2012, 14(11): 1032-1039.Kothny W, Shao Q, Groop PH, Lukashevich V. One-year safety, tolerability and efficacy of vildagliptin in patients with type 2 diabetes and moderate or severe renal impairment. Diabetes Obes Metab, 2012, 14(11): 1032-1039.McInnes G, Evans M, Del Prato S, Stumvoll M, Schweizer A, Lukashevich V, et al. Cardiovascular and heart failure safety profile of vildagliptin: a meta-analysis of 17 000 patients. Diabetes Obes Metab, 2015, 17(11): 1085-1092.McInnes G, Evans M, Del Prato S, Stumvoll M, Schweizer A, Lukashevich V, et al. Cardiovascular and heart failure safety profile of vildagliptin: a meta-analysis of 17 000 patients. Diabetes Obes Metab, 2015, 17(11): 1085-1092.Pratley RE, Schweizer A, Rosenstock J, Foley JE, Banerji MA, Pi-Sunyer FX, et al. Robust improvements in fasting and prandial measures of beta-cell function with vildagliptin in drug-naïve patients: analysis of pooled vildagliptin monotherapy database. Diabetes Obes Metab, 2008, 10(10): 931-938.Pratley RE, Schweizer A, Rosenstock J, Foley JE, Banerji MA, Pi-Sunyer FX, et al. Robust improvements in fasting and prandial measures of beta-cell function with vildagliptin in drug-naïve patients: analysis of pooled vildagliptin monotherapy database. Diabetes Obes Metab, 2008, 10(10): 931-938.Анциферов М.Б. Препараты Галвус и Галвусмет в терапии пожилых пациентов с сахарным диабетом 2 типа. Фарматека, 2011, 16: 69-74.Анциферов М.Б. Препараты Галвус и Галвусмет в терапии пожилых пациентов с сахарным диабетом 2 типа. Фарматека, 2011, 16: 69-74.Xidakis D, Antonaki E, Kostakis K, Tzanakakis M, Sfakianaki M, Papadogiannakis A. DPP-4 inhibitor, vildagliptin is effective in reducing albuminuria in early stages of diabetic nephropathy. Nephrol. Dial. Transplant, 2015, 30(suppl 3): iii535.Xidakis D, Antonaki E, Kostakis K, Tzanakakis M, Sfakianaki M, Papadogiannakis A. DPP-4 inhibitor, vildagliptin is effective in reducing albuminuria in early stages of diabetic nephropathy. Nephrol. Dial. Transplant, 2015, 30(suppl 3): iii535.Tani S, Nagao K, Hirayama A. Association between urinary albumin excretion and low-density lipoprotein heterogeneity following treatment of type 2 diabetes patients with the dipeptidyl peptidase-4 inhibitor, vildagliptin: a pilot study. Am J Cardiovasc Drugs, 2013, 13(6): 443-450.Tani S, Nagao K, Hirayama A. Association between urinary albumin excretion and low-density lipoprotein heterogeneity following treatment of type 2 diabetes patients with the dipeptidyl peptidase-4 inhibitor, vildagliptin: a pilot study. Am J Cardiovasc Drugs, 2013, 13(6): 443-450.Watanabe M, Furuya F, Kobayashi T. DPP-4 inhibitor vildagliptin reduces urinary albumin excretion in type 2 diabetic patients with microalbuminuria. Endocrine Abstracts, 2012, 29: P687.Watanabe M, Furuya F, Kobayashi T. DPP-4 inhibitor vildagliptin reduces urinary albumin excretion in type 2 diabetic patients with microalbuminuria. Endocrine Abstracts, 2012, 29: P687.Levey AS, Stevens LA, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med, 2009, 150: 604-612.Levey AS, Stevens LA, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med, 2009, 150: 604-612.KDIGO 2012 Clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney inter, 2013, 3: 1-150.KDIGO 2012 Clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney inter, 2013, 3: 1-150.Reutens AT, Atkins RC. Epidemiology of diabetic nephropathy. Contrib Nephrol, 2011, 170:1-7.Reutens AT, Atkins RC. Epidemiology of diabetic nephropathy. Contrib Nephrol, 2011, 170:1-7.Iijima T, Suzuki S, Sekizuka K, Hishiki T, Yagame M, Jinde K, et al. Follow-up study on urinary type IV collagen in patients with early stage diabetic nephropathy. J Clin Lab Anal, 1998, 12(6): 378-382.Iijima T, Suzuki S, Sekizuka K, Hishiki T, Yagame M, Jinde K, et al. Follow-up study on urinary type IV collagen in patients with early stage diabetic nephropathy. J Clin Lab Anal, 1998, 12(6): 378-382.Kado S, Aoki A, Wada S et al. Urinary type IV collagen as a marker for early diabetic nephropathy. Diabetes Research and Clinical Practice, 1996, 31(1–3): 103-108.Kado S, Aoki A, Wada S et al. Urinary type IV collagen as a marker for early diabetic nephropathy. Diabetes Research and Clinical Practice, 1996, 31(1–3): 103-108.Inoue M, Oishi C, Shimajiri Y, Furuta M, Ueyama M, Sanke T. Clinical usefulness of measurement of urine type IV collagen for detection of early phase of nephropathy in type 2 diabetic patients. Rinsho Byori, 2008, 56(7): 564-569.Inoue M, Oishi C, Shimajiri Y, Furuta M, Ueyama M, Sanke T. Clinical usefulness of measurement of urine type IV collagen for detection of early phase of nephropathy in type 2 diabetic patients. Rinsho Byori, 2008, 56(7): 564-569.Tomino Y, Suzuki S, Azushima S et al. Asian multicenter trials on urinary type IV collagen in patients with diabetic nephropathy. Journal of Clinical Laboratory Analysis, 2001, 15(4): 188-192.Tomino Y, Suzuki S, Azushima S et al. Asian multicenter trials on urinary type IV collagen in patients with diabetic nephropathy. Journal of Clinical Laboratory Analysis, 2001, 15(4): 188-192.Banu N, Hara H, Okamura M, Egusa G, Yamakido M. Urinary excretion of type IV collagen and laminin in the evaluation of nephropathy in NIDDM: comparison with urinary albumin and markers of tubular dysfunction and/or damage. Diabetes Res Clin Pract, 1995, 29(1): 57-67.Banu N, Hara H, Okamura M, Egusa G, Yamakido M. Urinary excretion of type IV collagen and laminin in the evaluation of nephropathy in NIDDM: comparison with urinary albumin and markers of tubular dysfunction and/or damage. Diabetes Res Clin Pract, 1995, 29(1): 57-67.Okonogi H, Nishimura M, Utsunomiya Y, Hamaguchi K, Tsuchida H, Miura Y, et al. Urinary type IV collagen excretion reflects renal morphological alterations and type IV collagen expression in patients with type 2 diabetes mellitus. Clin Nephrol, 2001, 55(5): 357-364.Okonogi H, Nishimura M, Utsunomiya Y, Hamaguchi K, Tsuchida H, Miura Y, et al. Urinary type IV collagen excretion reflects renal morphological alterations and type IV collagen expression in patients with type 2 diabetes mellitus. Clin Nephrol, 2001, 55(5): 357-364.Ming S, Qi Z, Wang L, and Zhu K. Urinary type IV collagen: a specific indicator of incipient diabetic nephropathy. Chinese Medical Journal, 2002, 115(3): 389-394.Ming S, Qi Z, Wang L, and Zhu K. Urinary type IV collagen: a specific indicator of incipient diabetic nephropathy. Chinese Medical Journal, 2002, 115(3): 389-394.Cohen-Bucay A, Viswanathan G. Urinary markers of glomerular injury in diabetic nephropathy. Int J Nephrol, 2012, 2012: 146987.Cohen-Bucay A, Viswanathan G. Urinary markers of glomerular injury in diabetic nephropathy. Int J Nephrol, 2012, 2012: 146987.Вельков В.В. Диабетическая нефропатия в трех измерениях: гиперфильтрация, альбумин, креатинин. В. В. Вельков (ред.). Лабораторна діагностика. К.:ТОВ « ДІА», 2012, 4: 50-72.Вельков В.В. Диабетическая нефропатия в трех измерениях: гиперфильтрация, альбумин, креатинин. В. В. Вельков (ред.). Лабораторна діагностика. К.:ТОВ « ДІА», 2012, 4: 50-72.Lukashevich V, Schweizer A, Shao Q, Groop PH, Kothny W. Safety and efficacy of vildagliptin versus placebo in patients with type 2 diabetes and moderate or severe renal impairment: a prospective 24-week randomized placebo-controlled trial. Diabetes Obes Metab, 2011, 13(10): 947-954.Lukashevich V, Schweizer A, Shao Q, Groop PH, Kothny W. Safety and efficacy of vildagliptin versus placebo in patients with type 2 diabetes and moderate or severe renal impairment: a prospective 24-week randomized placebo-controlled trial. Diabetes Obes Metab, 2011, 13(10): 947-954.Петунина Н.А. Снижение риска гипогликемий на фоне терапии вилдаглиптином: клинический опыт, данные исследований и преимущества при управлении сахарным диабетом 2-го типа. Лечащий врач, 2011, 3: 27.Петунина Н.А. Снижение риска гипогликемий на фоне терапии вилдаглиптином: клинический опыт, данные исследований и преимущества при управлении сахарным диабетом 2-го типа. Лечащий врач, 2011, 3: 27.Qiao Q, Tuomilehto J, Borch-Johnsen K. Postchallenge hyperglycaemia is associated with premature death and macrovascular complications. Diabetologia, 2003, 46(Suppl 1): M17-21.Qiao Q, Tuomilehto J, Borch-Johnsen K. Postchallenge hyperglycaemia is associated with premature death and macrovascular complications. Diabetologia, 2003, 46(Suppl 1): M17-21.Аметов А.С. Вилдаглиптин. Возможности оптимального контроля сахарного диабета 2-го типа. Сахарный диабет, 2015, 18(4): 125-129.Аметов А.С. Вилдаглиптин. Возможности оптимального контроля сахарного диабета 2-го типа. Сахарный диабет, 2015, 18(4): 125-129.Ahrén B, Schweizer A, Dejager S, Dunning BE, Nilsson PM, Persson M, et al. Vildagliptin enhances islet responsiveness to both hyper- and hypoglycemia in patients with type 2 diabetes. J Clin Endocrinol Metab, 2009, 94(4): 1236-1243.Ahrén B, Schweizer A, Dejager S, Dunning BE, Nilsson PM, Persson M, et al. Vildagliptin enhances islet responsiveness to both hyper- and hypoglycemia in patients with type 2 diabetes. J Clin Endocrinol Metab, 2009, 94(4): 1236-1243.Evans M, Schweizer A, Foley JE. Blood pressure and fasting lipid changes after 24 weeks’ treatment with vildagliptin: a pooled analysis in >2,000 previously drug-naïve patients with type 2 diabetes mellitus. Vasc Health Risk Manag, 2016, 12: 337-340.Evans M, Schweizer A, Foley JE. Blood pressure and fasting lipid changes after 24 weeks’ treatment with vildagliptin: a pooled analysis in >2,000 previously drug-naïve patients with type 2 diabetes mellitus. Vasc Health Risk Manag, 2016, 12: 337-340.Okajima F, Emoto N, Kato K, Sugihara H. Effect of Glycemic Control on Chylomicron Metabolism and Correlation between Postprandial Meta bolism of Plasma Glucose and Chylomicron in Patients with Type 2 Diabetes Treated withOkajima F, Emoto N, Kato K, Sugihara H. Effect of Glycemic Control on Chylomicron Metabolism and Correlation between Postprandial Meta bolism of Plasma Glucose and Chylomicron in Patients with Type 2 Diabetes Treated withBasal-bolus Insulin Therapy with or without Vildagliptin., Journal of Atherosclerosis and Thrombosis, 2017, 24(2): 157-168.Basal-bolus Insulin Therapy with or without Vildagliptin., Journal of Atherosclerosis and Thrombosis, 2017, 24(2): 157-168.Rosenstock J, Foley JE, Rendell M, Landin-Olsson M, Holst JJ, Deacon CF, et al. Effects of the dipeptidyl peptidase-IV inhibitor vildagliptin on incretin hormones, islet function, and postprandial glycemia in subjects with impaired glucose tolerance. Diabetes Care, 2008, 31(1): 30-35.Rosenstock J, Foley JE, Rendell M, Landin-Olsson M, Holst JJ, Deacon CF, et al. Effects of the dipeptidyl peptidase-IV inhibitor vildagliptin on incretin hormones, islet function, and postprandial glycemia in subjects with impaired glucose tolerance. Diabetes Care, 2008, 31(1): 30-35.Derosa G, Ragonesi PD, Carbone A, Fogari E, D’Angelo A, Cicero AF, et al. Vildagliptin action on some adipocytokine levels in type 2 diabetic patients: a 12-month, placebo-controlled study. Expert Opin Pharmacother, 2012, 13(18): 2581-2591.Derosa G, Ragonesi PD, Carbone A, Fogari E, D’Angelo A, Cicero AF, et al. Vildagliptin action on some adipocytokine levels in type 2 diabetic patients: a 12-month, placebo-controlled study. Expert Opin Pharmacother, 2012, 13(18): 2581-2591.Derosa G, Maffioli P, Ferrari I, Mereu R, Ragonesi PD, Querci F, et al. Effects of one year treatment of vildagliptin added to pioglitazone or glimepiride in poorly controlled type 2 diabetic patients. Horm Metab Res, 2010, 42(9): 663-669.Derosa G, Maffioli P, Ferrari I, Mereu R, Ragonesi PD, Querci F, et al. Effects of one year treatment of vildagliptin added to pioglitazone or glimepiride in poorly controlled type 2 diabetic patients. Horm Metab Res, 2010, 42(9): 663-669.Zografou I, Sampanis C, Gkaliagkousi E, Iliadis F, Papageorgiou A, Doukelis P, et al. Effect of vildagliptin on hsCRP and arterial stiffness in patients with type 2 diabetes mellitus. Hormones (Athens), 2015, 14(1): 118-125.Zografou I, Sampanis C, Gkaliagkousi E, Iliadis F, Papageorgiou A, Doukelis P, et al. Effect of vildagliptin on hsCRP and arterial stiffness in patients with type 2 diabetes mellitus. Hormones (Athens), 2015, 14(1): 118-125.Пчелин И.Ю., Шишкин А.Н., Лаптева О.А. Роль системного и локального воспаления в развитии диабетической нефропатии. Нефрология, 2011, 15(4): 21-26.Пчелин И.Ю., Шишкин А.Н., Лаптева О.А. Роль системного и локального воспаления в развитии диабетической нефропатии. Нефрология, 2011, 15(4): 21-26.Yousuf O, Mohanty BD, Martin SS, Joshi PH, Blaha MJ, Nasir K, et al. High-sensitivity C-reactive protein and cardiovascular disease: a resolute belief or an elusive link? J Am Coll Cardiol, 2013, 62(5): 397-408.Yousuf O, Mohanty BD, Martin SS, Joshi PH, Blaha MJ, Nasir K, et al. High-sensitivity C-reactive protein and cardiovascular disease: a resolute belief or an elusive link? J Am Coll Cardiol, 2013, 62(5): 397-408.Uzun S, Ozari M, Gursu M, Karadag S, Behlul A, Sari S, et al. Changes in the inflammatory markers with advancing stages of diabetic nephropathy and the role of pentraxin-3. Ren Fail, 2016, 38(8): 1193-1198.Uzun S, Ozari M, Gursu M, Karadag S, Behlul A, Sari S, et al. Changes in the inflammatory markers with advancing stages of diabetic nephropathy and the role of pentraxin-3. Ren Fail, 2016, 38(8): 1193-1198.Aso Y, Yoshida N, Okumura K, Wakabayashi S, Matsutomo R, Takebayashi K, et al. Coagulation and inflammation in overt diabetic nephropathy: association with hyperhomocysteinemia. Clin Chim Acta, 2004, 348(1-2): 139-145.Aso Y, Yoshida N, Okumura K, Wakabayashi S, Matsutomo R, Takebayashi K, et al. Coagulation and inflammation in overt diabetic nephropathy: association with hyperhomocysteinemia. Clin Chim Acta, 2004, 348(1-2): 139-145.Смирнов А.В., Добронравов В.А., Каюков И.Г. Кардио-ренальный континуум: патогенетические основы превентивной нефрологии. Нефрология, 2005, 91(3): 7-15.Смирнов А.В., Добронравов В.А., Каюков И.Г. Кардио-ренальный континуум: патогенетические основы превентивной нефрологии. Нефрология, 2005, 91(3): 7-15.Jindal A, Garcia-Touza M, Jindal N, WhaleyConnell A, Sowers JR. Diabetic kidney disease and the cardiorenal syndrome: old disease, new perspectives. Endocrinol Metab Clin North Am, 2013, 42(4): 789-808.Jindal A, Garcia-Touza M, Jindal N, WhaleyConnell A, Sowers JR. Diabetic kidney disease and the cardiorenal syndrome: old disease, new perspectives. Endocrinol Metab Clin North Am, 2013, 42(4): 789-808.

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