medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2018-5-58-63medsovet-2357Research ArticleСердечная недостаточностьHeart failureАнтагонисты минералокортикоидных рецепторов новые расширенные возможности для кардио- и нефропротекцииMineralocorticoid receptor antagonists: new extended roles in cardio- and nephroprotectionЕсаянА. М.EsayanA. M.

д.м.н., профессор

MD, Prof.

НимгироваА. Н.NimgirovaA. N.Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. ПавловаРоссияPavlov First Saint Petersburg State Medical UniversityRussian Federation201810042018055863Copyright © Есаян А.М., Нимгирова А.Н., 20182018Есаян А.М., Нимгирова А.Н.Esayan A.M., Nimgirova A.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/2357

В статье описаны современные представления о роли альдостерона в прогрессировании кардиоваскулярных и почечных заболеваний. Обсуждаются вопросы эффективности и безопасности антагонистов минералокортикоидных рецепторов у пациентов с хронической сердечной недостаточностью, на разных стадиях хронической болезни почек, включая терминальную почечную недостаточность, диализную терапию, трансплантацию почки.

 

The article presents the contemporary views of the role of aldosterone in the progression of cardiovascular and renal diseases. It addresses matters related to the efficacy and safety of mineralocorticoid receptor antagonists in patients with chronic heart failure, chronic kidney disease at various stages including terminal renal failure, dialysis therapy, and kidney transplantation.

 

альдостеронантагонисты минералокортикоидных рецепторовсердечная недостаточностьхроническая болезнь почекдиализтрансплантация почкиaldosteronemineralocorticoid receptor antagonistsheart failurechronic kidney diseasedialysiskidney transplantationReferenceshttp://www.who.int/mediacentre/factsheets/ fs355/en/.http://www.who.int/mediacentre/factsheets/ fs355/en/.Herzog CA, Asinger RW, Berger AK et al. Cardiovascular disease in chronic kidney disease. A clinical update from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int, 2011, 80: 572–586.Herzog CA, Asinger RW, Berger AK et al. Cardiovascular disease in chronic kidney disease. A clinical update from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int, 2011, 80: 572–586.Coresh J, Byrd-Holt D, Astor BC, et al. Chronic kidney disease awareness, prevalence, and trends among U.S. adults, 1999 to 2000. J Am Soc Nephrol, 2005, 16: 180-188.Coresh J, Byrd-Holt D, Astor BC, et al. Chronic kidney disease awareness, prevalence, and trends among U.S. adults, 1999 to 2000. J Am Soc Nephrol, 2005, 16: 180-188.Chudek et al. The prevalence of chronic kidney disease and its relation to socioeconomic conditions in an elderly Polish population: results from the national population-based study PolSenior. Nephrol Dial Transplant, 2014, 29: 1073–1082.Chudek et al. The prevalence of chronic kidney disease and its relation to socioeconomic conditions in an elderly Polish population: results from the national population-based study PolSenior. Nephrol Dial Transplant, 2014, 29: 1073–1082.Foley RN, Parfrey PS, Sarnak MJ. Epidemiology of cardiovascular disease in chronic renal disease. J Am Soc Nephrol, 1998, 9(12 suppl): 16–23.Foley RN, Parfrey PS, Sarnak MJ. Epidemiology of cardiovascular disease in chronic renal disease. J Am Soc Nephrol, 1998, 9(12 suppl): 16–23.Карабаева А.Ж. Альдостерон, сердечно-сосудистая система и почки. Нефрология, 2006, 1(10): 25-34Karabaeva AZh. Aldosterone, cardiovascular system and kidneys. Nefrologiya, 2006, 1 (10): 25-34Fander JW. Minireview: Aldosterone and Mineralocorticoid Receptors: Past, Present, and Future. Endocrinology, 2010, 151(11): 5098-5102.Fander JW. Minireview: Aldosterone and Mineralocorticoid Receptors: Past, Present, and Future. Endocrinology, 2010, 151(11): 5098-5102.Brown NJ. Contribution of aldosterone to cardiovascular and renal inflammation and fibrosis. Nat Rev Nephrol, 2013, 9(8): 459–69. 10.1038/nrneph.2013.110.Brown NJ. Contribution of aldosterone to cardiovascular and renal inflammation and fibrosis. Nat Rev Nephrol, 2013, 9(8): 459–69. 10.1038/nrneph.2013.110.Rossi GP, Sachetto A, Visentin P. et al. Changes in left ventricular anatomy and function in hypertension and primary aldosteronism. Hypertension, 1996, 27: 1039–1045.Rossi GP, Sachetto A, Visentin P. et al. Changes in left ventricular anatomy and function in hypertension and primary aldosteronism. Hypertension, 1996, 27: 1039–1045.Halimi J-M, Mimram A. Albuminuria in untreated patients with primary aldosteronism or essential hypertension. J Hypertens, 1995, 13: 1801–1802.Halimi J-M, Mimram A. Albuminuria in untreated patients with primary aldosteronism or essential hypertension. J Hypertens, 1995, 13: 1801–1802.Nishimura M, Uzu T, Fuji T et al. Cardiovascular complications in patients with primary aldosteronism. Am J Kidney Dis, 1999, 33: 261–266.Nishimura M, Uzu T, Fuji T et al. Cardiovascular complications in patients with primary aldosteronism. Am J Kidney Dis, 1999, 33: 261–266.Weber KT, Brilla CG, Campbell SE et al. Myocardial fibrosis – role of angiotensin II and aldosterone. Basic Res Cardiol, 1993, 88(Suppl 1): 107–124.Weber KT, Brilla CG, Campbell SE et al. Myocardial fibrosis – role of angiotensin II and aldosterone. Basic Res Cardiol, 1993, 88(Suppl 1): 107–124.Young M, Head G, Funder JW. Determinants of cardiac fibrosis in experimental hypermineralocorticoid states. Am J Physiol, 1995, 269: E657–E662.Young M, Head G, Funder JW. Determinants of cardiac fibrosis in experimental hypermineralocorticoid states. Am J Physiol, 1995, 269: E657–E662.Stier CT. Eplerenone: a selective aldosterone blocker. Cardiovasc Drug Rev, 2003, 21(3): 169–84. 10.1111/j.1527-3466.2003.tb00114.xStier CT. Eplerenone: a selective aldosterone blocker. Cardiovasc Drug Rev, 2003, 21(3): 169–84. 10.1111/j.1527-3466.2003.tb00114.xRocha R, Funder JW. The pathophysiology of aldosterone in the cardiovascular system. Ann N Y Acad Sci, 2002, 970: 89–100.Rocha R, Funder JW. The pathophysiology of aldosterone in the cardiovascular system. Ann N Y Acad Sci, 2002, 970: 89–100.Карабаева А.Ж., Есаян А.М., Каюков И.Г. Влияние полиморфизма гена альдостерон-синтазы на концентрацию альдостерона плазмы, функцию эндотелия, величину артериального давления и состояние миокарда левого желудочка у больных с хронической болезнью почек. Вестник Санкт-Петербургского университета, 2008, 1(серия 11): 24-31Karabaeva AZh., Yesayan AM., Kayukov IG. Effect of aldosterone synthase gene polymorphism on plasma aldosterone concentration, endothelial function, blood pressure value and left ventricular myocardium in patients with chronic kidney disease. Vestnik Sankt-Peterburgskogo Universiteta, 2008, 1 (series 11): 24-31.Mortensen LA, Bistrup C, Thiesson HC. Does Mineralocorticoid Receptor Antagonism Prevent Calcineurin Inhibitor-Induced Nephrotoxicity? Front Med, 2017, 4: 210. doi: 10.3389/fmed.2017.00210.Mortensen LA, Bistrup C, Thiesson HC. Does Mineralocorticoid Receptor Antagonism Prevent Calcineurin Inhibitor-Induced Nephrotoxicity? Front Med, 2017, 4: 210. doi: 10.3389/fmed.2017.00210.Карабаева А.Ж. Дисфункция эндотелия в патогенезе сердечно-сосудистых заболеваний. Терапевтический вестник, 2006, 3(11): 22-27Karabaeva AZh. Endothelial dysfunction in the pathogenesis of cardiovascular diseases. Terapevticheskiy Vestnik, 2006, 3 (11): 22-27Funder JW. Minireview: aldosterone and miner-alocorticoid receptors: past, present, and future. Endocrinology, 2010, 151(11): 5098–5102.Funder JW. Minireview: aldosterone and miner-alocorticoid receptors: past, present, and future. Endocrinology, 2010, 151(11): 5098–5102.Карабаева А.Ж., Есаян А.М., Каюков И.Г. и соавт. Влияние спиронолактона на гипертрофию миокарда левого желудочка у крыс генетической линии Wistar с экспериментальной уремией. Бюллетень экспериментальной биологии и медицины, 2008, 6: 659-663Karabaeva AZh., Yesayan AM, Kayukov IG, et al. The impact of spironolactone on left ventricular myocardial hypertrophy in Wistar rats with experimental uremia. Byulleten’ Eksperimental’noy Biologii i Meditsiny, 2008, 6: 659-663Guichard JL, Clark D III, Caloun DA. Aldosterone receptor antagonists: current perspectives and therapies. Vasc Health Risk Manag, 2013, 9: 321-31.Guichard JL, Clark D III, Caloun DA. Aldosterone receptor antagonists: current perspectives and therapies. Vasc Health Risk Manag, 2013, 9: 321-31.Fuller PJ, Young MJ. Mechanisms of mineralocorticoid action. Hypertension, 2005, 46: 1227-1246.Fuller PJ, Young MJ. Mechanisms of mineralocorticoid action. Hypertension, 2005, 46: 1227-1246.Ponda MP, Hostetter ThH. Aldosterone antagonism in chronic kidney disease. Clin J Am Soc Nephrol, 2006, 1: 668-667.Ponda MP, Hostetter ThH. Aldosterone antagonism in chronic kidney disease. Clin J Am Soc Nephrol, 2006, 1: 668-667.Galuppo P, Bauersachs J. Mineralocorticoid receptor activation in myocardial infarction and failure: Recent advances. Eur J Clin Invest, 2012, 42: 1112–1120.Galuppo P, Bauersachs J. Mineralocorticoid receptor activation in myocardial infarction and failure: Recent advances. Eur J Clin Invest, 2012, 42: 1112–1120.Messaoudi S, Azibani F, Delcayre C, Jaisser F. Aldosterone, mineralocorticoid receptor, and heart failure. Mol Cell Endocrinol, 2012, 350: 266–272.Messaoudi S, Azibani F, Delcayre C, Jaisser F. Aldosterone, mineralocorticoid receptor, and heart failure. Mol Cell Endocrinol, 2012, 350: 266–272.Roger VL. Epidemiology of Heart Failure. Circ Res, 2013 August 30, 113(6): 646–659.Roger VL. Epidemiology of Heart Failure. Circ Res, 2013 August 30, 113(6): 646–659.Foley RN, Murray AM, Li S, et al. Chronic kidney disease and the risk for cardiovascular disease, renal replacement, and death in the United States Medicare population, 1998 to 1999. J Am Soc Nephrol, 2005, 16: 489–95.Foley RN, Murray AM, Li S, et al. Chronic kidney disease and the risk for cardiovascular disease, renal replacement, and death in the United States Medicare population, 1998 to 1999. J Am Soc Nephrol, 2005, 16: 489–95.Parfrey PS, Harnett JD, Foley RN. Heart failure and ischemic heart disease in chronic uremia. Curr Opin Nephrol Hypertens, 1995, 4: 105–10.Parfrey PS, Harnett JD, Foley RN. Heart failure and ischemic heart disease in chronic uremia. Curr Opin Nephrol Hypertens, 1995, 4: 105–10.Pitt B, Zannad F, Remme WJ,et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators.N Engl J Med, 1999 Sep 2, 341(10): 709-17.Pitt B, Zannad F, Remme WJ,et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators.N Engl J Med, 1999 Sep 2, 341(10): 709-17.Pitt B, Remme W, Zannad F, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med, 2003, 348: 1309-1321.Pitt B, Remme W, Zannad F, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med, 2003, 348: 1309-1321.Zannad F, McMurray JJ, Drexler H et al. Rationale and design of the Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure (EMPHASIS-HF). Eur J Heart Fail, 2010, 12: 617-622.Zannad F, McMurray JJ, Drexler H et al. Rationale and design of the Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure (EMPHASIS-HF). Eur J Heart Fail, 2010, 12: 617-622.Rossi GP et al. Long-term control of arterial hypertension and regression of left ventricular hypertrophy with treatment of primary aldosteronism. Hypertension, 2013, 62: 62-69.Rossi GP et al. Long-term control of arterial hypertension and regression of left ventricular hypertrophy with treatment of primary aldosteronism. Hypertension, 2013, 62: 62-69.Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation, 2013, 128: e240–e327.Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation, 2013, 128: e240–e327.Williams B, MacDonald TM, Morant S, et al. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2):a randomised, double-blind, crossover trial. Lancet, 2015, 386: 2059–2068.Williams B, MacDonald TM, Morant S, et al. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2):a randomised, double-blind, crossover trial. Lancet, 2015, 386: 2059–2068.Piontkowski P, Voors A, Anker S, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. European Heart Journal, 2016, 37(27): 2129–2200.Piontkowski P, Voors A, Anker S, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. European Heart Journal, 2016, 37(27): 2129–2200.Juurlink DN, Mamdani MM, et al. Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study. N Engl J Med, 2004, 351:543–51.Juurlink DN, Mamdani MM, et al. Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study. N Engl J Med, 2004, 351:543–51.Cruz CS, Cruz AA, Marcilio de Souza CA. Hyperkalaemia in congestive heart failure patients using ACE inhibitors and spironolactone. Nephrol Dial Transplant. 2003, 18: 1814–1819.Cruz CS, Cruz AA, Marcilio de Souza CA. Hyperkalaemia in congestive heart failure patients using ACE inhibitors and spironolactone. Nephrol Dial Transplant. 2003, 18: 1814–1819.Schepkens H, Vanholder R, Billiouw JM, Lameire N. Life-threatening hyperkalemia during combined therapy with angiotensin-converting enzyme inhibitors and spironolactone: an analysis of 25 cases. Am J Med, 2001, 110: 438–441.Schepkens H, Vanholder R, Billiouw JM, Lameire N. Life-threatening hyperkalemia during combined therapy with angiotensin-converting enzyme inhibitors and spironolactone: an analysis of 25 cases. Am J Med, 2001, 110: 438–441.Lauren B. Cooper, MD, MHS, Steven J. Use of Mineralocorticoid Receptor Antagonists in Patients With Heart Failure and Comorbid Diabetes Mellitus or Chronic Kidney Disease. JAHA, 2017, 6: e006540. DOI: 10.1161/ JAHA.117.006540.Lauren B. Cooper, MD, MHS, Steven J. Use of Mineralocorticoid Receptor Antagonists in Patients With Heart Failure and Comorbid Diabetes Mellitus or Chronic Kidney Disease. JAHA, 2017, 6: e006540. DOI: 10.1161/ JAHA.117.006540.Dahal K, Kunwar S, Rijal J et al. The effects of aldosterone antagonists in patients with resistant hypertension: a meta-analysis of random-ized and nonrandomized studies. Am J Hypertens, 2015. DOI: http://dx.doi.org/10.1093/ajh/hpv031.Dahal K, Kunwar S, Rijal J et al. The effects of aldosterone antagonists in patients with resistant hypertension: a meta-analysis of random-ized and nonrandomized studies. Am J Hypertens, 2015. DOI: http://dx.doi.org/10.1093/ajh/hpv031.Epstein M, Williams GH, Weinberger M, Lewin A, Krause S, Mukherjee R, Patni R, Beckerman B. Selective aldosterone blockade with eplere-none reduces albuminuria in patients with type 2 diabetes. Clin J Am Soc Nephrol, 2006, 1: 940–951.Epstein M, Williams GH, Weinberger M, Lewin A, Krause S, Mukherjee R, Patni R, Beckerman B. Selective aldosterone blockade with eplere-none reduces albuminuria in patients with type 2 diabetes. Clin J Am Soc Nephrol, 2006, 1: 940–951.James PA, Oparil S, Carter BL et al. 2014 evidence‐based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA, 2014, 311: 507–520.James PA, Oparil S, Carter BL et al. 2014 evidence‐based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA, 2014, 311: 507–520.Bolignano D, Palmer SC, Navaneethan SD, Strippoli GF. Aldosterone antagonists for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev, 2014, 4: Cd007004.Bolignano D, Palmer SC, Navaneethan SD, Strippoli GF. Aldosterone antagonists for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev, 2014, 4: Cd007004.Rafiq K, Hitomi H, Nakano D, et al. Pathophysiological roles of aldosterone and mineralocorticoid receptor in the kidney. J Pharmacol Sci, 2011, 115: 1-7.Rafiq K, Hitomi H, Nakano D, et al. Pathophysiological roles of aldosterone and mineralocorticoid receptor in the kidney. J Pharmacol Sci, 2011, 115: 1-7.Bomback AS, Klemmer PJ. The incidence and implications of aldosterone breakthrough. Nat Clin Pract Nephrol, 2007 Sep, 3(9): 486-92.Bomback AS, Klemmer PJ. The incidence and implications of aldosterone breakthrough. Nat Clin Pract Nephrol, 2007 Sep, 3(9): 486-92.Bomback AS, Kshirsagar AV, Klemmer PJ. Renal aspirin: will all patients with chronic kidney disease one day take spironolactone? Nat Clin Pract Nephrol, 2009, 5: 74–5.Bomback AS, Kshirsagar AV, Klemmer PJ. Renal aspirin: will all patients with chronic kidney disease one day take spironolactone? Nat Clin Pract Nephrol, 2009, 5: 74–5.Bomback AS, et al. Change in proteinuria after adding aldosterone blockers to ACE inhibitors or angiotensin receptor blockers in CKD: a systematic review. Am J Kidney Dis, 2008, 51: 199–211.Bomback AS, et al. Change in proteinuria after adding aldosterone blockers to ACE inhibitors or angiotensin receptor blockers in CKD: a systematic review. Am J Kidney Dis, 2008, 51: 199–211.Monrad SU, Killen PD, Anderson MR, Bradke A, Kaplan MJю The role of aldosterone blockade in murine lupus nephritis. Arthritis Res Ther, 2008, 10(1): R5.Monrad SU, Killen PD, Anderson MR, Bradke A, Kaplan MJю The role of aldosterone blockade in murine lupus nephritis. Arthritis Res Ther, 2008, 10(1): R5.Saran R, Li Y, Robinson B et al. US Renal Data System 2014 Annual Data Report: epidemiology of kidney disease in the United States. Am J Kidney Dis, 2015, 66: Svii(S1-S305).Saran R, Li Y, Robinson B et al. US Renal Data System 2014 Annual Data Report: epidemiology of kidney disease in the United States. Am J Kidney Dis, 2015, 66: Svii(S1-S305).Harnett JD, Foley RN, Kent GM, Barre PE, Murray D and Parfrey PS. Congestive heart failure in dialysis patients: prevalence, incidence, prognosis and risk factors. Kidney Int, 1995, 47: 884–890.Harnett JD, Foley RN, Kent GM, Barre PE, Murray D and Parfrey PS. Congestive heart failure in dialysis patients: prevalence, incidence, prognosis and risk factors. Kidney Int, 1995, 47: 884–890.Есаян А.М., Карабаева А.Ж., Каюков И.Г. Кандинская М.И. Ассоциация полиморфизма гена альдостеронсинтазы с концентрацией альдостерона плазмы, артериальной гипертензией и ремоделированием миокарда у больных на программном гемодиализе. Нефрология, 2007, 11(3): 48-52./Esayan AM, Karabaeva AZh., Kayukov IG. Kandinskaya MI. Association of aldosterone synthase gene poly-morphism with plasma aldosterone concentration, arterial hypertension and myocardial remodeling in patients on programmed hemo-dialysis. Nefrologiya, 2007, 11 (3): 48-52Есаян А.М., Зарипова И.В. Эффективность и безопасность блокаторов рецепторов ангиотензина II у диализных пациентов. Нефро логия, 2010, 14(3): 13-16Esayan AM, Zaripova IV. Efficacy and safety of angiotensin II receptor blockers in dialysis patients. Nefrologiya, 2010, 14 (3): 13-16Есаян А.М., Зарипова И.В., Каюков И.Г., Нимгирова А.Н. Динамика концентрации калия в сыворотке крови на фоне «трехкомпонентной» и «двухкомпонентной» фармакологической блокады ренин-ангиотензин-альдостероновой системы у больных на постоянном гемо-диализе. Нефрология, 2011, 15(1): 43-45Esayan AM, Zaripova IV, Kayukov IG, Nimgirova AN. Dynamics of potassium concentration in the blood serum against the background of the «three-component» and «two-component» pharmacological blockade of the renin-angiotensinaldosterone system in patients on permanent hemodialysis. Nefrologiya, 2011, 15 (1): 43-45Saudan P, Mach F, Perneger Th et al. Safety of low-dose spironolactone administration in chronic haemodialysis patients. Nephrol Dial Transplant, 2003, 18: 2359-2363.Saudan P, Mach F, Perneger Th et al. Safety of low-dose spironolactone administration in chronic haemodialysis patients. Nephrol Dial Transplant, 2003, 18: 2359-2363.Gross E, Rothstein M, Dombek S, Juknis HI. Effect of Spironolactone on Blood Pressure and the Renin-Angiotensin-Aldosterone System in Oligo-Anuric Hemodialysis Patients. Am J Kidney Dis, 2005, 46(1): 94-101.Gross E, Rothstein M, Dombek S, Juknis HI. Effect of Spironolactone on Blood Pressure and the Renin-Angiotensin-Aldosterone System in Oligo-Anuric Hemodialysis Patients. Am J Kidney Dis, 2005, 46(1): 94-101.Карабаева А.Ж., Есаян А.М., Каюков И.Г. и соавт. Влияние терапии спиронолактоном на уровень альдостерона и дисфункцию эндотелия у больных на программном гемодиализе. Нефрология, 2007, 2(11): 55-58Karabaeva AZh, Yesayan AM, Kayukov IG, et al. The impact of spironolactone therapy on aldosterone levels and endothelial dysfunction in patients on programmed hemodialysis. Nefrologiya, 2007, 2 (11): 55-58Essaian A, Kaukov I, Karabayeva A, Kadinskaya M, Katysheva N. The influence of spironolac-tone on plasma level of plasminogen-activator inhibitor type 1 (PAI-1) in anuric hemodyalisis patients.- XLIV Congress ERA-EDTA (Barcelona). Nephrol Dial Transpl, 2007, 22(Suppl. 6): vi322.Essaian A, Kaukov I, Karabayeva A, Kadinskaya M, Katysheva N. The influence of spironolac-tone on plasma level of plasminogen-activator inhibitor type 1 (PAI-1) in anuric hemodyalisis patients.- XLIV Congress ERA-EDTA (Barcelona). Nephrol Dial Transpl, 2007, 22(Suppl. 6): vi322.Есаян А.М, Карабаева А.Ж., Каюков И.Г. Показатели эхокардиографии у больных с хронической болезнью почек и их динамика под влиянием терапии спиронолактоном. Нефрология, 2008, 1(12): 40-45Esayan AM, Karabaeva AZh, Kayukov IG. Echocardiography parameters in patients with chronic kidney disease and dynamics of such parameters under the impact of spironolactone therapy. Nefrologiya, 2008, 1 (12): 40-45Карабаева А.Ж., Есаян А.М., Каюков И.Г. Заявка на изобретение № 2007119515 РФ, МПК 7 А 61 К 31/585, А 61 З 9/10 «Способ профилактики и лечения кардиоваскулярных осложнений у больных с хронической болез-нью почек, находящихся на гемодиализе». Заявлено 27.05.2007, опубликовано в бюллетене № 33 от 27.11.2008Karabaeva AZh, Yesayan AM, Kayukov IG. Claim for invention No. 2007119515 RF, IPC 7 A 61 K 31/585, A 61 Z 9/10 «The method for preventing and treating cardiovascular complications in patients with chronic kidney disease who are on hemo-dialysis.» Applied 27.05.2007, published in Bulletin No. 33 dated 27.11.2008Зарипова И.В., Есаян А.М., Нимгирова А.Н., Каюков И.Г. Динамика концентрации калия в сыворотке крови на фоне «трехкомпонентной» и «двухкомпонентной» фармакологической блокады ренин-ангиотензин-альдостероновой системы у больных на постоянном гемодиализе. Нефрология, 2011, 15(1): 43-45Zaripova IV, Yesayan AM, Nimgirova AN, Kayukov IG. The dynamics of changes in serum potassium concentrations against the background of the «three-component» and «two-component» pharmacological blockade of the renin-angiotensinaldosterone system in patients on permanent hemodialysis. Nefrologiya, 2011, 15 (1): 43-45Taheri S, Mortazavi M, Shahidi S, et al. Spironolactone in chronic hemodialysis patients improves cardiac function. Saudi J Kidney Dis Transpl, 2009, 20: 392-397.Taheri S, Mortazavi M, Shahidi S, et al. Spironolactone in chronic hemodialysis patients improves cardiac function. Saudi J Kidney Dis Transpl, 2009, 20: 392-397.Taheri S, Mortazavi M, Pourmoghadas A, et al. A prospective double-blind randomized placebo-controlled clinical trial to evaluate the safety and efficacy of spironolactone in patients with advanced congestive heart failure on continuous ambulatory peritoneal dialysis. Saudi J Kidney Dis Transpl, 2012, 23: 507-512.Taheri S, Mortazavi M, Pourmoghadas A, et al. A prospective double-blind randomized placebo-controlled clinical trial to evaluate the safety and efficacy of spironolactone in patients with advanced congestive heart failure on continuous ambulatory peritoneal dialysis. Saudi J Kidney Dis Transpl, 2012, 23: 507-512.Matsumoto Y, Mori Y, Kageyama S, et al. Spironolactone reduces cardiovascular and cerebrovascular morbidity and mortality in hemodialysis patients. J Am Coll Cardiol, 2014, 63: 528-536.Matsumoto Y, Mori Y, Kageyama S, et al. Spironolactone reduces cardiovascular and cerebrovascular morbidity and mortality in hemodialysis patients. J Am Coll Cardiol, 2014, 63: 528-536.Vukusich A, Kunstmann S, Varela C, et al. A Randomized, Double-Blind, Placebo-Controlled Trial of Spironolactone on Carotid Intima-Media Thickness in Nondiabetic Hemodialysis Patients. JASN, 2010, 5(8): 1380-1387.Vukusich A, Kunstmann S, Varela C, et al. A Randomized, Double-Blind, Placebo-Controlled Trial of Spironolactone on Carotid Intima-Media Thickness in Nondiabetic Hemodialysis Patients. JASN, 2010, 5(8): 1380-1387.ClinicalTrials.gov Identifier: NCT01848639.ClinicalTrials.gov Identifier: NCT01848639.Haas M. Chronic allograft nephropathy or interstitial fibrosis and tubular atrophy: what is in a name? Current Opinion in Nephrology & Hypertension, 2014, 23(3): 245–250. doi: 10.1097/01.mnh.0000444811.26884.2d.Haas M. Chronic allograft nephropathy or interstitial fibrosis and tubular atrophy: what is in a name? Current Opinion in Nephrology & Hypertension, 2014, 23(3): 245–250. doi: 10.1097/01.mnh.0000444811.26884.2d.Rigatto C, Foley R, Jeffery J et al. Electrocardiographic Left Ventricular Hypertrophy in Renal Transplant Recipients: Prognostic Value and Impact of Blood Pressure and Anemia. JASN, 2003, 14(2): 462-468.Rigatto C, Foley R, Jeffery J et al. Electrocardiographic Left Ventricular Hypertrophy in Renal Transplant Recipients: Prognostic Value and Impact of Blood Pressure and Anemia. JASN, 2003, 14(2): 462-468.Есаян А.М., Каюков И.Г., Нимгирова А.Н. и др. Фактор роста фибробластов 23-го типа у реципиентов почечного аллотрансплантата. Нефрология, 2012, 4: 50-54Esayan AM, Kayukov IG, Nimgirova AN, at al. Fibroblast growth factor-23 in renal transplant recipients. Nefrologiya, 2012, 4: 50-54Naesens M, Kuypers DR, Sarwal M. Calcineurin inhibitor nephrotoxicity. Clin J Am Soc Nephrol, 2009, 4(2): 481–508.10.2215/CJN.04800908Naesens M, Kuypers DR, Sarwal M. Calcineurin inhibitor nephrotoxicity. Clin J Am Soc Nephrol, 2009, 4(2): 481–508.10.2215/CJN.04800908Perez-Rojas JM, Derive S, Blanco JA, et al. Renocortical mRNA expression of vasoactive factors during spironolactone protective effect in chronic cyclosporine nephrotoxicity. Am J Physiol Renal Physiol, 2005, 289(5): F1020–30. 10.1152/ajprenal.00166.2005.Perez-Rojas JM, Derive S, Blanco JA, et al. Renocortical mRNA expression of vasoactive factors during spironolactone protective effect in chronic cyclosporine nephrotoxicity. Am J Physiol Renal Physiol, 2005, 289(5): F1020–30. 10.1152/ajprenal.00166.2005.Nielsen FT, Jensen BL, Marcussen N, et al. Inhibition of mineralocorticoid receptors with eplere-none alleviates short-term cyclosporin A nephro-toxicity in conscious rats. Nephrol Dial Transplant, 2008, 23(9): 2777–83. 10.1093/ndt/gfn204.Nielsen FT, Jensen BL, Marcussen N, et al. Inhibition of mineralocorticoid receptors with eplere-none alleviates short-term cyclosporin A nephro-toxicity in conscious rats. Nephrol Dial Transplant, 2008, 23(9): 2777–83. 10.1093/ndt/gfn204.Nielsen FT, Jensen BL, Hansen PB, et al. The min-eralocorticoid receptor antagonist eplerenone reduces renal interstitial fibrosis after long-term cyclosporine treatment in rat: antagonizing cyclosporine nephrotoxicity. BMC Nephrol, 2013, 14: 42. 10.1186/1471-2369-14-42.Nielsen FT, Jensen BL, Hansen PB, et al. The min-eralocorticoid receptor antagonist eplerenone reduces renal interstitial fibrosis after long-term cyclosporine treatment in rat: antagonizing cyclosporine nephrotoxicity. BMC Nephrol, 2013, 14: 42. 10.1186/1471-2369-14-42.Bertocchio JP, Barbe C, Lavaud S, Toupance O, et al. Safety of Eplerenone for kidney-transplant recipients with impaired renal function and receiving cyclosporine A. PLoS One, 2016, 11(4): e0153635.10.1371/journal.pone.0153635.Bertocchio JP, Barbe C, Lavaud S, Toupance O, et al. Safety of Eplerenone for kidney-transplant recipients with impaired renal function and receiving cyclosporine A. PLoS One, 2016, 11(4): e0153635.10.1371/journal.pone.0153635.Medeiros M, Velasquez-Jones L, Hernandez AM et al. Randomized controlled trial of mineralocorticoid receptor blockade in children with chronic kidney allograft nephropathy. Clin J Am Soc Nephrol, 2017, 12(8): 1291–300. 10.2215/ CJN.05300516.Medeiros M, Velasquez-Jones L, Hernandez AM et al. Randomized controlled trial of mineralocorticoid receptor blockade in children with chronic kidney allograft nephropathy. Clin J Am Soc Nephrol, 2017, 12(8): 1291–300. 10.2215/ CJN.05300516.

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