За пределами контроля гликемии: нефропротективные эффекты агонистов рецепторов глюкагоноподобного пептида 1


DOI: https://dx.doi.org/10.18565/nephrology.2021.3.84-91

М.Ш. Шамхалова, И.А. Скляник, М.В. Шестакова

ФГБУ «НМИЦ эндокринологии» Минздрава РФ, Москва, Россия
Хроническая болезнь почек у пациентов с сахарным диабетом (СД) – лидирующая причина терминальной почечной недостаточности (ТПН), определяющая высокий риск сердечно-сосудистой патологии и смертности. Успехи в лечении СД не отменяют риски ТПН, а сдвигают их в соответствии с возрастом и длительностью заболевания. Современные сахароснижающие препараты – агонисты рецепторов глюкагоноподобного пептида 1 (арГПП-1), эффективно контролирующие гликемию, компоненты метаболического синдрома, значимо снижающие риск первичной 3-компонентной конечной точки (МАСЕ), по данным крупных исследований сердечно-сосудистой безопасности, обладают недооцененным нефропротективным потенциалом. Ренальные эффекты арГПП-1 определены противовоспалительными, антиапоптотическими, антиоксидантными возможностями препаратов этой группы. В статье представлен анализ исследований, посвященных изучению свойств арГПП-1.
Ключевые слова: агонисты рецепторов глюкагоноподобного пептида 1, сахарный диабет, нефропротекция, хроническая болезнь почек
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Литература


  1. Koye D.N., Magliano D.J., Nelson R.G., Pavkov M.E. The global epidemiology of diabetes and kidney disease. Adv. Chronic Kidney Dis. 2018;25(2):121–32.

  2. Fox C.S., Matsushita K., Woodward M., et al. Associations of kidney diseases measures with mortality and end-stage renal disease in individuals with and without diabetes: a meta-analysis. Lancet. 2012;10;380(98540):1662–73.

  3. Tonneijck L., Muskiet M.H., Smits M.M., et al. Glomerular hyperfiltration in diabetes: mechanisms, clinical significance, and treatment. J. Am. Soc. Nephrol. 2017;28:1023–39.

  4. Осложнения сахарного диабета. Лечение и профилактика. Под ред. И.И. Дедова и М.В. Шестаковой. М., 2017. 744 с. 

  5. Afrarian M., Zelnick L.R., Hall Y.N., et al. Clinical manifestations of kidney disease fmong US adults with diabetes, 1988–2014. JAMA. 2016;316(6):602–10.

  6. Shyangdan D.S., Royle P., Clar C., et al. Glucagonlike peptide analogues for type 2 diabetes malloitus. Cochrane Database Syst. Rev. 2011;CD006423.

  7. Nauck M. Incretin therapies: highlighting common features and differences in the modes of action of glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors. Diab. Obes. Metab. 2016;18:203–16.

  8. Smits M.M., van Raalte D.H., Tonneijck L., et al. GLP-1 based therapies: clinical implications for gastroenterologists. Gut. 2016;65:702–11.

  9. Bethel M.A., Patel R.A., Merrill P., et al. Cardiovascular outcomes with glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes: meta-analysis. Lancet. Diab. Endocrinol. 2018;6(2):105–13.

  10. American Diabetes Association. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes – 2021. Diab. Care. 2021;44(Suppl. 1):S111–24. Doi: 10.2337/dc21-S009.

  11. Avgerinos I., Karaqiannis T., Malandris K., et al. Glucagon-like peptide-1 receptor agonists and microvascular outcomes in type 2 diabetes: a systematic review and metaanalysis. Diabetes Obes Metab 2019;21:188–193

  12. Dicembrini I., Nreu B., Scatena A., et al. Microvascular effects of glucagon-like peptide-1 receptor agonists in type 2 diabetes: a meta-analysis of randomized controlled trials. Acta Diabetol. 2017;54:933–41.

  13. Kristensen S.L., Rørth R., Jhund P.S., et al. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet. Diab. Endocrinol. 2019;7(10):776–85.

  14. Sattar N., Lee M.M.Y., Kristensen S.L., et al. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of randomized trials. L-ancet Diabetes Endocrinol. 2021;9:953–662.

  15. Greco E.V., Russo G., Giandalia A., et al. GLP-1 receptor agonist and kidney protection. Med. 2019;55:233. Doi: 10.3390/medicina55060233.

  16. Skov J., Dejgaard A., Frokiaer J., et al. Glucagonlike peptide-1 (GLP-1): effect on kidney hemodynamics and renin-angiotensin-aldosterone system in healthy men. J. Clin. Endocrinol. Metab. 2013;98:E664–71.

  17. Asmar A., Simonsen L., Asmar M., et al. Renal extraction and acute effects of glucagon-like peptide-1 on central and renal hemodynamics in healthy men. Am. J. Physiol. Endocrinol. Metab. 2015;308:E641–49.

  18. Gutzwiller J.P., Tschopp S., Bock A., et al. Glucagonlike peptide 1 induces natriuresis in healthy subjects and in insulin-resistant obese men. J. Clin. Endocrinol. Metab. 2004;89:89:3055–61.

  19. Muskiet M.H., Tonneijck L., Smits M.M., et al. Acute renal haemodynamic effects of glucagonlike peptide-1 receptor agonist exenatide in healthy overweight men. Diab. Obes. Metab. 2016;18:178–85.

  20. Tonneijck L., Smits M.M., Muskiet M.H., et al. Acute renal effects of the GLP-1 receptor agonist exenatide in overweight type 2 diabetes patients: a randomised, double-blind, placebo-controlled trial. Diabetol. 2016;59:1412–21.

  21. Skov J., Pedersen M., Holst J.J., et al. Shortterm effects of liraglutide on kidney function and vasoactive hormones in type 2 diabetes: a randomized clinical trial. Diab. Obes. Metab. 2016;18:581–89.

  22. Kim M., Platt M.J., Shibasaki T., et al. GLP-1 receptor activation and Epac2 link atrial natriuretic peptide secretion to control of blood pressure. Nat. Med. 2013;19:567–75.

  23. Tonneijck L., Smits M.M., Muskiet M.H., et al. Renal effects of DPP-4 inhibitor sitagliptin or GLP-1 receptor agonist liraglutide in overweight patients with type 2 diabetes: a 12-week, randomized, double-blind, placebocontrolled trial. Diab. Care. 2016;39:2042–50.

  24. Fujita H., Morii T., Fujishima H., et al. The protective roles of GLP-1R signaling in diabetic nephropathy: Possible mechanism and therapeutic potential. Kidney Int. 2014;85:579–89.

  25. Tanaka T., Higashijima Y., Wada T., Nangaku M. The potential for renoprotection with incretin-based drugs. Kidney Int. 2014;86:701–11.

  26. Thomas M.C. The potential and pitfalls of GLP-1 receptor agonists for renal protection in type 2 diabetes. Diab. Metab. 2017;43(Suppl. 1):2S20–7.

  27. Farah L.X., Valentini V., Pessoa T.D., et al. The physiological role of glucagon-like peptide-1 in the regulation of renal function. Am. J. Physiol. Renal. Physiol. 2016;310:F123–27.

  28. Muskiet M.H., Smits M.M., Morsink L.M., et al. The gut-renal axis: do incretin-based agents confer renoprotection in diabetes? Nat. Rev. Nephrol. 2014;10:88–103.

  29. Von Scholten B.J., Hansen T.W., Goetze J.P., et al. Glucagon-like peptide 1 receptor agonist (GLP-1 RA): long-term effect on kidney function in patients with type 2 diabetes. J. Diab. Complicat. 2015;29:670–74.

  30. Pyke C., Heller R.S., Kirk R.K., et al. GLP-1 receptor localization in monkeyand human tissue: novel distribution revealed with extensively validated monoclonal antibody. Endocrinol. 2014;155:1280–90.

  31. Van Baar M.J.D., van der Art A.B., Hoogenberg K., et al. The incretin pathway as a therapeutic target in diabetic kidney disease: a clinical focus on GLP-1 receptor agonists. Ther. Adv. Endocrinol. Metab. 2019;10:1–11.

  32. Von Scholten B.J., Lajer M., Goetze J.P., et al. Time course and mechanisms of the anti-hypertensive and renal effects of liraglutide treatment. Diab. Med. 2015;32:343–52.

  33. Davies M.J., Bain S.C., Atkin S.L., et al. Efficacy and safety of liraglutide versus placebo as add-on to glucose-lowering therapy in patients with type 2 diabetes and moderate renal impairment (LIRARENAL): a randomized clinical trial. Diab. Care 2016;39:222–30.

  34. Tuttle K.R., Heilmann C., Hoogwerf B.J., et al. Effects of exenatide on kidney function, adverse events, and clinical end points of kidney disease in type 2 diabetes. Am. J. Kidney Dis. 2013;62:396–98.

  35. Tuttle K.R., McKinney T.D., Davidson J.A., et al. Effects of once-weekly dulaglutide on kidney function in patients with type 2 diabetes in phase II and III clinical trials. Diab. Obes. Metab. 2017;19:436–41.

  36. Von Scholten B.J., Persson F., Rosenlund S., et al. The effect of liraglutide on renal function: a randomized clinical trial. Diab. Obes. Metab. 2017;19:239–47.

  37. Tonneijck L., Muskiet M.H.A., Smits M.M., et al. Postprandial renal haemodynamic effect of lixisenatide versus once-daily insulin glulisine in type 2 diabetes patients on insulin-glargine: an 8-week, randomised, open-label trial. Diab. Obes. Metab. 2017;19:1669–80.

  38. Lee Y.S., Jun H.S. Anti-inflammatory effects of GLP-1-based therapies beyond glucose control. Mediat. Inflamm. 2016. https:// doi.org/10.1155/2016/3094642.

  39. Deb D.K., Bao R., Li Y.C. Critical role of the cAMP-PKA pathway in hyperglycemia-induced epigenetic activation of fibrogenic program in the kidney. FASEB. J. 2017;31:2065–75.

  40. Kodera R., Shikata K., Kataoka H.U., et al. Glucagon-like peptide-1 receptor agonist ameliorates renal injury through its anti-inflammatory action without lowering blood glucose level in a rat model of type 1 diabetes. Diabetol. 2011;54:965–78.

  41. Hendarto H., Inoguchi T., Maeda Y., et al. GLP-1 analog liraglutide protects against oxidative stress and albuminuria in streptozotocin-induced diabetic rats via protein kinase A-mediated inhibition of renal NAD(P)H oxidases. Metab. 2012;61:1422–34.

  42. Sourris K.C., Yao H., Jerums G., et al. Can targeting the incretin pathway dampen RAGE-mediated events in diabetic nephropathy? Curr. Drug Targets. 2016;17:1252–64.

  43. Xin W., Li Z., Xu Y., et al. Autophagy protects human podocytes from high glucose-induced injury by preventing insulin resistance. Metab. 2016;65(9):1307–15.

  44. Yang H., Li H., Wang Z., et al. Exendin-4 ameliorates renal ischemia-reperfusion injury in the rat. J. Surg. Res. 2013;185:825–32.

  45. Wang C., Li L., Liu S., et al. GLP-1 receptor agonist ameliorates obesity-induced chronic kidney injury via restoring renal metabolism homeostasis. PLoS ONE. 2018;13:0193473.

  46. Roscioni S.S., Heerspink H.J., de Zeeuw D. The effect of RAAS blockade on the progression of diabetic nephropathy. Nat. Rev. Nephrol. 2014;10:77–87.

  47. Sircana A., De Michieli F., Parente R., et al. Gut microbiota, hypertension and chronic kidney disease: recent advances. Pharmacol. Res. 2019;144:390–408.

  48. Wang L., Li P., Tang Z., et al. Structural modulation of the gut microbiota and the relationship with body weight: compared evaluation of liraglutide and saxagliptin treatment. Sci. Rep. 2016;6:33251. Doi: 10.1038/srep33251.

  49. KDIGO 2020. Clinical practice guideline for diabetes mellitus management in chronic kidney disease. Kidney Intern. 2020;98:S1–115.

  50. Клинические рекомендации Российской ассоциации эндокринологов «Сахарный диабет 2 типа у взрослых» 2019. Сахарный диабет. 2020;23(Suppl. 1). 

  51. Pfeffer M.A., Claggett B., Diaz R., et al. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N. Engl. J. Med. 2015;373:2247–57.

  52. Marso S.P., Daniels G.H., Brown-Frandsen K., et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N. Engl. J. Med. 2016;375:311–22.

  53. Bethel M.A., Mentz R.J., Merrill P., et al. Renal outcomes in the EXenatide study of cardiovascular event lowering (EXSCEL) (Abstract). Diab. 2018;67(Suppl. 1):A522.

  54. Hernandez A.F., Green J.B., Janmohamed S, et al. Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-dlind, randomised placebo-controlled trial. Lancet. 2018;392:1519–29.

  55. Gerstein H.C., Colhoun H.M., Dagenais G.R., et al. Dulaglutide and renal outcomes in type 2 diabetes: an exploratory analysis of the REWIND randomized, placebo-controlled trial. Lancet. 2019;394(10193):131–38.

  56. Marso S.P., Bain S.C., Consoli A., et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N. Engl. J. Med. 2016;375:1834–44.

  57. Zoungas S., Arima H., Gerstein H.C., et al. Effects of intensive glucose control on microvascular outcomes in patients with type 2 diabetes: a meta-analysis of individual participant data from randomized controlled trials. Lancet. Diab. Endocrinol. 2017;5:431–37.

  58. Xie X., Atkins E., Lv J., et al. Effects of intensive blood pressure lowering on cardiovascular and renal outcomes: updated systematic review and meta-analysis. Lancet. 2016;387:435–43.

  59. Mann J.F., Hansen T., Idorn T., et al. Effects of once-weekly subcutaneous on kidney function and safety in patients with type 2 diabetes: a post-hoc analysis of the SUSTSAIN 1-7 randomised controlled trials. Lancet. Diab. Endocrinol. 2020;8:880–93.


Об авторах / Для корреспонденции

Шамхалова Минара Шамхаловна – д.м.н., ФГБУ «НМИЦ эндокринологии» Минздрава РФ, Москва, Россия; e-mail: shamkhalova@mail.ru.
ORCID: https://orcid.org/0000-0002-3433-0142; eLibrary SPIN: 4942-5481.
Скляник Игорь Александрович – научный сотрудник, ФГБУ «НМИЦ эндокринологии» Минздрава РФ, Москва, Россия; e-mail: sklyanik.igor@gmail.com.
ORCID: https://orcid.org/0000-0002-7768-4717; eLibrary SPIN: 7081-8077.
Шестакова Марина Владимировна –д.м.н., профессор, академик РАН ФГБУ «НМИЦ эндокринологии» Минздрава РФ, Москва, Россия; e-mail: nephro@endocrincentr.ru. ORCID: https://orcid.org/0000-0002-5057-127X; eLibrary SPIN: 7584-7015.


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