Nephroprotective effects of sodium-glucose linked transporter-2 inhibitors


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Abstract

The article presents data on the mechanisms and clinical significance of the nephroprotective effect of sodium-glucose linked transporter-2 inhibitors (glyflozines). the effects associated with the influence of representatives of this pharmacological group on the glomerular filtration rate, glycemic level, diuresis, ketogenesis and other factors are discussed. the results of recent experimental and clinical studies aimed at studying certain aspects of the nephroprotective effect of sglt2 inhibitors in type 2 diabetes mellitus and other pathological conditions are analyzed.

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About the authors

B. T. Daminov

Tashkent Pediatric Medical Institute; Republican Specialized Scientific and Practical Medical Center for Nephrology and Kidney Transplantation

Email: nefrologiya2019@mail.ru
Dr. Sci. (Med.), Professor at the Department of Faculty Internal Diseases, Occupational Pathology, MFT, Hospital Internal Diseases and PID, Tashkent Pediatric Medical Institute; Director of the Republican Specialized Scientific and Practical Medical Center for Nephrology and Kidney Transplantation

Sh. S Abdullaev

Tashkent Pediatric Medical Institute

Email: dr.sherzod@rambler.ru
Dr. Sci. (Med.), Associate Professor at the Department of Faculty Internal Diseases, Occupational Pathology, MFT, Hospital Internal Diseases and PID, Tashkent Pediatric Medical Institute

O. N Sharapov

Tashkent Pediatric Medical Institute; Republican Specialized Scientific and Practical Medical Center for Nephrology and Kidney Transplantation

Email: olimkhon@gmail.com
Doctoral Student at the Department of Faculty Internal Diseases, Occupational Pathology, MFT, Hospital Internal Diseases and PID, Tashkent Pediatric Medical Institute; Nephrologist at the Republican Specialized Scientific and Practical Medical Center of Nephrology and Kidney Transplantation

References

  1. Thrasher J. Pharmacologic Management of Type 2 Diabetes Mellitus: Available Therapies. Am. J. Cardiol. 2017;120(1):S4-S16. Doi: 10.1016/j. amjcard.2017.05.009.
  2. Демидова Т.Ю. Сосудистые осложнения сахарного диабета 2 типа за гранью гликемического контроля. Сахарный диабет. 2016;3:111-116.
  3. Bonadonna R.C., Borghi C., Consoli A., Volpe M. Novel antidiabetic drugs and cardiovascular risk: Primum non nocere. Nutr. Metab. Cardiovasc. Dis. 2016;26:759-766. doi: 10.1016/j.numecd.2016.05.007.
  4. Satoh H. Pleiotropic effects of SGLT2 inhibitors beyond the effect on glycemic control. Diabetol. Int. 2018;9:212-214. doi: 10.1007/s1334018-0367-x.
  5. 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;15:114-118. doi: 10.15277/bjdvd.2015.031.
  6. Prie D. Familial renal glycosuria and modifications of glucose renal excretion. Diabetes Metab. 2014;40(1):S12-S16. Doi: 10.1016/ S1262-3636(14)72690-4.
  7. Vallon V. The mechanisms and therapeutic potential of SGLT2 inhibitors in diabetes mellitus. Annu. Rev. Med. 2015;66:255-270. doi: 10.1146/annurev-med-051013-110046.
  8. Maldonado-Cervantes M.I., Galicia O.G., Moreno-Jaime B. et al. Autocrine modulation of glucose transporter SGLT2 by IL-6 and TNF-a in LLC-PK1 cells. J. Physiol. Biochem. 2012;68:411-420. doi: 10.1007/s13105-012-0153-3.
  9. 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;8:e54442. doi: 10.1371/journal.pone.0054442.
  10. Vallon V., Thomson S.C. Targeting renal glucose reabsorption to treat hypergly-caemia: the pleiotropic effects of SGLT2 inhibition. Diabetologia. 2017;60:215-225. doi: 10.1007/s00125-016-4157-3.
  11. Gembardt F., Bartaun C., Jarzebska N. et al. The SGLT2 inhibitor empa-gliflozin ameliorates early features of diabetic nephropathy in BTBR ob/ob type 2 diabetic mice with and without hypertension. Am. J. Physiol. Renal Physiol. 2014;307:F317-F325. doi: 10.1152/ajprenal.00145.2014.
  12. 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;47:686-692. doi: 10.1055/s-0034-1395609.
  13. 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;24:e100777. doi: 10.1371/journal.pone.0100777.
  14. 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;4:e00239. Doi: 10.1002/ prp2.239.
  15. 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.
  16. Kawanami D., Matoba K., Takeda Y. et al. SGLT2 Inhibitors as a Therapeutic Option for Diabetic Nephropathy. Int. J. Mol. Sci. 2017;18:E1083. doi: 10.3390/ijms18051083.
  17. 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;1864:2021-2033. doi: 10.1016/j.bbadis.2018.03.017.
  18. 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;3:e12436. doi: 10.14814/phy2.12436.
  19. 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;137:220-223. doi: 10.1016/j.jphs.2017.10.006.
  20. 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;11:e0144640. doi: 10.1371/journal.pone.0144640.
  21. 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;830:68-75. doi: 10.1016/j.ejphar.2018.04.024.
  22. 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;5:e13228. doi: 10.14814/phy2.13228.
  23. Chang Y.-K., Choi H, Jeong J.Y. et al. Dapagliflozin, SGLT2 Inhibitor, attenuates renal ischemia-reperfusion injury. PLoS ONE. 2016;11:e0158810. doi: 10.1371/journal.pone.0158810.
  24. Zapata-Morales J.R., Galicia-Cruz O.G., Franco M., Morales F.M. Hypoxia-inducible factor-1a (HIF-1a) protein diminishes sodium glucose transport 1 (SGLT1) and SGLT2protein expression in renal epithelial tubular cells (LLC-PK1) under hypoxia. J. Biol. Chem. 2014;289:346-357. doi: 10.1074/jbc. M113.526814.
  25. Shimazu T., Hirschey M.D., Newman J. et al. Suppression of oxidative stress by beta-hydroxybutyrate, an endogenous histone deacetylase inhibitor. Science. 2013;339:211-214. doi: 10.1126/science.1227166.
  26. 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;39:1115-1122. Doi: 10.2337/ dc16-0542.
  27. 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;6:691-704. Doi: 10.1016/ S2213-8587(18)30141-4.
  28. 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.
  29. 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;42:318-326. Doi: 10.2337/ dc18-1871.
  30. 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;19:1106-1115. doi: 10.1111/dom.12917
  31. 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;129:587-597. Doi: 10.1161/ CIRCULA TIONAHA.113.005081.
  32. Gomez D.M. Evaluation of renal resistances, with special reference to changes in essential hypertension. J. Clin. Invest. 1951;30:1143-1155.
  33. 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;57:2599-2602. doi: 10.1007/s00125-014-3396-4.
  34. 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;2:1988-1993. doi: 10.1111/dom.13301.
  35. 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;20:2532-2540. doi: 10.1111/dom.13413.
  36. 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;12:751-759. doi: 10.2215/CJN.10180916.
  37. U. S. National Library of Medicine Clinical Trials Database. URL: https:// clinicaltrials.gov.

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