МЕХАНИЗМЫ И КЛИНИЧЕСКОЕ ЗНАЧЕНИЕ НЕФРОПРОТЕКТИВНОГО ДЕЙСТВИЯ ИНГИБИТОРОВ НАТРИЙ-ГЛЮКОЗНОГО КОТРАНСПОРТЁРА 2 ТИПА


Авторы

  • И. Ю. Пчелин Санкт-Петербургский государственный университет
  • О. Н. Василькова Гомельский государственный медицинский университет
  • А. Н. Шишкин Санкт-Петербургский государственный университет
  • В. К. Байрашева Национальный медицинский исследовательский центр им. В.А. Алмазова
  • Н. В. Худякова Санкт-Петербургский государственный университет

Ключевые слова:

сахарный диабет, пероральные сахароснижающие препараты, ингибиторы натрий-глюкозного котранспортёра 2 типа, ингибиторы SGLT2, хроническая болезнь почек, диабетическая нефропатия, нефропротекция

Аннотация

В статье представлены данные о механизмах и клиническом значении нефропротективного действия ингибиторов натрий-глюкозного котранспортёра 2 типа (SGLT2). Обсуждаются эффекты, связанные с влиянием представителей данной фармакологической группы на скорость клубочковой фильтрации, уровень гликемии, диурез, кетогенез и другие факторы. Проанализированы результаты недавно проведённых экспериментальных и клинических исследований, направленных на изучение отдельных аспектов нефропротективного действия ингибиторов SGLT2 при сахарном диабете 2 типа и других патологических состояниях.

Библиографические ссылки

Thrasher J. Pharmacologic Management of Type 2 Diabetes Mellitus: Available Therapies // Am. J. Cardiol. 2017. Vol. 120. S. 1. P. S4-S16. doi: 10.1016/j.amjcard.2017.05.009.

Демидова Т.Ю. Сосудистые осложнения сахарного диабета 2 типа за гранью гликемического контроля // Сахарный диабет. 2010. №3. С. 111-116.

Muskiet M.H., Tonneijck L., Smits M.M. et al. Pleiotropic effects of type 2 diabetes management strategies on renal risk factors // Lancet Diabetol. Endocrinol. 2015. Vol. 3. P. 367-381. doi: 10.1016/S2213-8587(15)00030-3.

Bonadonna R.C., Borghi C., Consoli A., Volpe M. Novel antidiabetic drugs and cardiovascular risk: Primum non nocere // Nutr. Metab. Cardiovasc. Dis. 2016. Vol. 26. P. 759-766. doi: 10.1016/j.numecd.2016.05.007.

Vallianou N.G., Geladari E., Kazazis C.E. SGLT-2 inhibitors: Their pleiotropic properties // Diabetes Metab. Syndr. 2017. Vol. 11. P. 311-315. doi: 10.1016/j.dsx.2016.12.003.

Satoh H. Pleiotropic effects of SGLT2 inhibitors beyond the effect on glycemic control // Diabetol. Int. 2018. Vol. 9. P. 212-214. doi: 10.1007/s13340-018-0367-x.

Maltese G., Abou-Saleh A., Gnudi L., Karalliedde J. Preventing diabetic renal disease: the potential reno-protective effects of SGLT2 inhibitors // Br. J. Diabetes Vasc. Dis. 2015. Vol. 15. P. 114-118. doi: 10.15277/bjdvd.2015.031.

Prie D. Familial renal glycosuria and modifications of glucose renal excretion // Diabetes Metab. 2014. Vol. 40. S. 1. P. S12-S16. doi: 10.1016/S1262-3636(14)72690-4.

Vallon V. The mechanisms and therapeutic potential of SGLT2 inhibitors in diabetes mellitus // Annu. Rev. Med. 2015. Vol. 66. P. 255-270. doi: 10.1146/annurev-med-051013-110046.

Maldonado-Cervantes M.I., Galicia O.G., Moreno-Jaime B. et al. Autocrine modulation of glucose transporter SGLT2 by IL-6 and TNF-α in LLC-PK1 cells // J. Physiol. Biochem. 2012. Vol. 68. P. 411-420. doi: 10.1007/s13105-012-0153-3.

Panchapakesan U., Pegg K., Gross S. et al. Effects of SGLT2 inhibition in human kidney proximal tubular cells – renoprotection in diabetic nephropathy? // PLoS One. 2013. Vol. 8. e54442. doi: 10.1371/journal.pone.0054442.

Vallon V., Thomson S.C. Targeting renal glucose reabsorption to treat hyperglycaemia: the pleiotropic effects of SGLT2 inhibition // Diabetologia. 2017. Vol. 60. P. 215-225. doi: 10.1007/s00125-016-4157-3.

Malatiali S., Francis I., Barac-Nieto M. Phlorizin prevents glomerular hyperfiltration but not hypertrophy in diabetic rats // Exp. Diabetes Res. 2008. Vol. 2008. ID305403. doi: 10.1155/2008/305403.

Osorio H., Coronel I., Arellano A. et al. Sodium-glucose cotransporter inhibition prevents oxidative stress in the kidney of diabetic rats // Oxid. Med. Cell. Longev. 2012. Vol. 2012. ID542042. doi: 10.1155/2012/542042.

Wakisaka M., Nagao T., Yoshinari M. Sodium glucose cotransporter 2 (SGLT2) plays as a physiological glucose sensor and regulates cellular contractility in rat mesangial cells // PLoS ONE. 2016. Vol. 11. e0151585. doi: 10.1371/journal.pone.0151585.

Gembardt F., Bartaun C., Jarzebska N. et al. The SGLT2 inhibitor empagliflozin ameliorates early features of diabetic nephropathy in BTBR ob/ob type 2 diabetic mice with and without hypertension // Am. J. Physiol. Renal Physiol. 2014. Vol. 307. P. F317-F325. doi: 10.1152/ajprenal.00145.2014.

Gallo L.A., Ward M.S., Fotheringham A.K. et al. Once daily administration of the SGLT2 inhibitor, empagliflozin, attenuates markers of renal fibrosis without improving albuminuria in diabetic db/db mice // Sci Rep. 2016. Vol. 26. e26428. doi: 10.1038/srep26428.

Gangadharan Komala M., Gross S., Mudaliar H. et al. Inhibition of kidney proximal tubular glucose reabsorption does not prevent against diabetic nephropathy in type 1 diabetic eNOS knockout mice // PLoS One. 2014. Vol. 9. e108994. doi: 10.1371/journal.pone.0108994.

Ojima A., Matsui T., Nishino Y. et al. Empagliflozin, an Inhibitor of Sodium-Glucose Cotransporter 2 Exerts Anti-Inflammatory and Antifibrotic Effects on Experimental Diabetic Nephropathy Partly by Suppressing AGEs-Receptor Axis // Horm. Metab. Res. 2015. Vol. 47. P. 686-692. doi: 10.1055/s-0034-1395609.

Terami N., Ogawa D., Tachibana H. et al. Long-term treatment with the sodium glucose cotransporter 2 inhibitor, dapagliflozin, ameliorates glucose homeostasis and diabetic nephropathy in db/db mice // PLoS One. 2014. Vol. 24. e100777. doi: 10.1371/journal.pone.0100777.

Hatanaka T., Ogawa D., Tachibana H. et al. Inhibition of SGLT2 alleviates diabetic nephropathy by suppressing high glucose-induced oxidative stress in type 1 diabetic mice // Pharmacol. Res. Perspect. 2016. Vol. 4. e00239. doi: 10.1002/prp2.239 .

Nagata T., Fukuzawa T., Takeda M. et al. Tofogliflozin, a novel sodium-glucose co-transporter 2 inhibitor, improves renal and pancreatic function in db/db mice // Br. J. Pharmacol. 2013. Vol. 170. P. 519-531. doi: 10.1111/bph.12269.

Kawanami D., Matoba K., Takeda Y. et al. SGLT2 Inhibitors as a Therapeutic Option for Diabetic Nephropathy // Int. J. Mol. Sci. 2017. Vol. 18. P. E1083. doi: 10.3390/ijms18051083.

Jaikumkao K., Pongchaidecha A., Chueakula N. et al. Renal outcomes with sodium glucose cotransporter 2 (SGLT2) inhibitor, dapagliflozin, in obese insulin-resistant model // Biochim. Biophys. Acta. 2018. Vol. 1864. P. 2021-2033. doi: 10.1016/j.bbadis.2018.03.017.

Kojima N., Williams J.M., Slaughter T.N. et al. Renoprotective effects of combined SGLT2 and ACE inhibitor therapy in diabetic Dahl S rats // Physiol. Rep. 2015. Vol. 3. e12436. doi: 10.14814/phy2.12436.

Li L., Konishi Y., Morikawa T. et al. Effect of a SGLT2 inhibitor on the systemic and intrarenal renin-angiotensin system in subtotally nephrectomized rats // J. Pharm Sci. 2018. Vol. 137. P. 220-223. doi: 10.1016/j.jphs.2017.10.006.

Zhang Y., Thai K., Kepecs D.M., Gilbert R.E. Sodium-glucose linked cotransporter-2 inhibition does not attenuate disease progression in the rat remnant kidney model of chronic kidney disease // PLoS ONE. 2016. Vol. 11. e0144640. doi: 10.1371/journal.pone.0144640.

Tahara A., Takasu T. Prevention of progression of diabetic nephropathy by the SGLT2 inhibitor ipragliflozin in uninephrectomized type 2 diabetic mice // Eur. J. Pharmacol. 2018. Vol. 830. P. 68-75. doi: 10.1016/j.ejphar.2018.04.024.

Ma Q., Steiger S., Anders H.J. Sodium glucose transporter-2 inhibition has no renoprotective effects on non-diabetic chronic kidney disease // Physiol. Rep. 2017. Vol. 5. e13228. doi: 10.14814/phy2.13228.

Chang Y.-K., Choi H., Jeong J.Y. et al. Dapagliflozin, SGLT2 Inhibitor, attenuates renal ischemia-reperfusion injury // PLoS ONE. 2016. Vol. 11. e0158810. doi: 10.1371/journal.pone.0158810.

Zapata-Morales J.R., Galicia-Cruz O.G., Franco M., Morales F.M. Hypoxia-inducible factor-1α (HIF-1α) protein diminishes sodium glucose transport 1 (SGLT1) and SGLT2 protein expression in renal epithelial tubular cells (LLC-PK1) under hypoxia // J. Biol. Chem. 2014. Vol. 289. P. 346-357. doi: 10.1074/jbc.M113.526814.

Shimazu T., Hirschey M.D., Newman J. et al. Suppression of oxidative stress by beta-hydroxybutyrate, an endogenous histone deacetylase inhibitor // Science. 2013. Vol. 339. P. 211-214. doi: 10.1126/science.1227166.

Guder W.G., Wagner S., Wirthensohn G. Metabolic fuels along the nephron: pathways and intracellular mechanisms of interaction // Kidney Int. 1986. Vol. 29. P. 41-45.

Wanner C., Inzucchi S.E., Zinman B. et al. Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes // N. Engl. J. Med. 2016. Vol. 375. P. 323-334. doi: 10.1056/NEJMc1611290.

Mudaliar S., Alloju S., Henry R.R. Can a Shift in Fuel Energetics Explain the Beneficial Cardiorenal Outcomes in the EMPA-REG OUTCOME Study? A Unifying Hypothesis // Diabetes Care. 2016. Vol. 39. P. 1115-1122. doi: 10.2337/dc16-0542.

Perkovic V., de Zeeuw D., Mahaffey K.W. et al. Canagliflozin and renal outcomes in type 2 diabetes: results from the CANVAS Program randomised clinical trials // Lancet Diabetes Endocrinol. 2018. Vol. 6. P. 691-704. doi: 10.1016/S2213-8587(18)30141-4.

Wiviott S.D., Raz I., Bonaca M.P. et al. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes // N. Engl. J. Med. 2018. Nov 10. [Epub ahead of print]. doi: 10.1056/NEJMoa1812389.

Clegg L.E., Heerspink H.J.L., Penland R.C. et al. Reduction of Cardiovascular Risk and Improved Estimated Glomerular Filtration Rate by SGLT2 Inhibitors, Including Dapagliflozin, Is Consistent Across the Class: An Analysis of the Placebo Arm of EXSCEL // Diabetes Care. 2019. Vol. 42. P. 318-326. doi: 10.2337/dc18-1871.

Tang H., Li D., Zhang J. et al. Sodium-glucose co-transporter-2 inhibitors and risk of adverse renal outcomes among patients with type 2 diabetes: A network and cumulative meta-analysis of randomized controlled trials // Diabetes Obes. Metab. 2017. Vol. 19. P. 1106-1115. doi: 10.1111/dom.12917

Cherney D.Z., Perkins B.A., Soleymanlou N. et al. Renal hemodynamic effect of sodium-glucose cotransporter 2 inhibition in patients with type 1 diabetes mellitus // Circulation. 2014. Vol. 129. P. 587-597. doi: 10.1161/CIRCULATIONAHA.113.005081.

Gomez D.M. Evaluation of renal resistances, with special reference to changes in essential hypertension // J. Clin. Invest. 1951. Vol. 30. P. 1143-1155.

Skrtic M., Yang G.K., Perkins B.A. Characterisation of glomerular haemodynamic responses to SGLT2 inhibition in patients with type 1 diabetes and renal hyperfiltration // Diabetologia. 2014. Vol. 57. P. 2599-2602. doi: 10.1007/s00125-014-3396-4.

Dekkers C.C.J., Petrykiv S., Laverman G.D. et al. Effects of the SGLT-2 inhibitor dapagliflozin on glomerular and tubular injury markers // Diabetes Obes Metab. 2018. Vol. 20. P. 1988-1993. doi: 10.1111/dom.13301.

Fioretto P., Del Prato S., Buse J.B. et al. Efficacy and safety of dapagliflozin in patients with type 2 diabetes and moderate renal impairment (chronic kidney disease stage 3A): The DERIVE Study // Diabetes Obes. Metab. 2018. Vol. 20. P. 2532-2540. doi: 10.1111/dom.13413.

Petrykiv S., Sjostrom C.D., Greasley P.J. Differential Effects of Dapagliflozin on Cardiovascular Risk Factors at Varying Degrees of Renal Function // Clin. J. Am. Soc. Nephrol. 2017. Vol. 12. P. 751-759. doi: 10.2215/CJN.10180916.

U. S. National Library of Medicine Clinical Trials Database. URL: https://clinicaltrials.gov.

Lewin A., DeFronzo R.A., Patel S. et al. Initial combination of empagliflozin and linagliptin in subjects with type 2 diabetes // Diabetes Care. 2015. Vol. 38. P. 394-402. doi: 10.2337/dc14-2365.

Muller M.E., Pruijm M., Bonny O. et al. Effects of the SGLT-2 Inhibitor Empagliflozin on Renal Tissue Oxygenation in Non-Diabetic Subjects: A Randomized, Double-Blind, Placebo-Controlled Study Protocol // Adv Ther. 2018. Vol. 35. P. 875-885. doi: 10.1007/s12325-018-0708-y.

Rajasekeran H., Reich H.N., Hladunewich M.A. et al. Dapagliflozin in focal segmental glomerulosclerosis: a combined human-rodent pilot study // Am. J. Physiol. Renal Physiol. 2018. Vol. 314. P. F412-F422. doi: 10.1152/ajprenal.00445.2017.

Mordi N.A., Mordi I.R., Singh J.S. Renal and Cardiovascular Effects of sodium-glucose cotransporter 2 (SGLT2) inhibition in combination with loop Diuretics in diabetic patients with Chronic Heart Failure (RECEDE-CHF): protocol for a randomised controlled double-blind cross-over trial // BMJ Open. 2017. Vol. 7. E018097. doi: 10.1136/bmjopen-2017-018097.

Загрузки


Просмотров аннотации: 11

Опубликован

30.01.2019

Как цитировать

1.
Пчелин И.Ю., Василькова О.Н., Шишкин А.Н., Байрашева В.К., Худякова Н.В. МЕХАНИЗМЫ И КЛИНИЧЕСКОЕ ЗНАЧЕНИЕ НЕФРОПРОТЕКТИВНОГО ДЕЙСТВИЯ ИНГИБИТОРОВ НАТРИЙ-ГЛЮКОЗНОГО КОТРАНСПОРТЁРА 2 ТИПА // Juvenis Scientia. 2019. № 1. сс. 4-9.

Выпуск

Раздел

ОБЗОРНЫЕ СТАТЬИ

Наиболее читаемые статьи этого автора (авторов)

1 2 3 > >>