В работе изучены нефропротективный, гипотензивный и сосудистый эффекты фиксированной комбинации лизиноприла и амлодипина у 24 больных сахарным диабетом (СД) типа 2 и артериальной гипертензией (АГ) с микроальбуминурией. Длительность лечения составила 24 нед. Оценивали влияние терапии на уровень альбуминурии, скорость клубочковой фильтрации, офисное и среднесуточное АД, степень эндотелийзависимой вазодилатации (ЭЗВД) и результаты активной ортостатической пробы. По окончании исследования отмечено достоверное снижение альбуминурии на 47,0%, отношения альбумин/креатинин мочи – на 51,8%, офисного АД – на 18,7/15,7 мм рт. ст., среднесуточного АД – на 9,9/7,5 мм рт. ст. Нормоальбуминурия достигнута у 10 человек (41,7%), целевой уровень АД<130/80 мм рт. ст. – у 15 (62,5%). Скорость клубочковой фильтрации не изменялась. Отмечена тенденция к увеличению ЭЗВД на 3,4%. При этом не нарастала ортостатическая гипотензия. Таким образом, терапия фиксированной комбинацией лизиноприла и амлодипина эффективно уменьшает экскрецию альбумина с мочой и АД, а также улучшает функциию эндотелия у больных диабетической и гипертензивной нефропатией.
The aimof the study was to investigate renoprotective, vascular and antihypertensive ef-fects of the lisinopril and amlodipine fixed combination in type 2 diabetes and arterial hyperten-sion patients with microalbuminuria (n=24). The study duration was 24 weeks. Urinary albumin concentration, glomerular filtration rate, office and average daily BP levels, endothelium-dependent vasodilatation (EDVD) test and orthostatic BP reduction were evaluated under the influence of selected therapy. At the end of the study urinary albumin excretion was significantly reduced by 47,0%, albumin/creatinine ratio – by 51,8%, office BP – by 18,7/15,7 and diurnal BP – by 9,9/7,5 mm Hg. Normoalbuminuria was achieved in 10 persons (41,7%), target BP<130/80 mm Hg – in 15 (62,5%). Glomerular filtration rate did not change. We also revealed the trend to EDVD increase by 3,4%. At the same time the orthostatic hypotension did not rise. Thus, the fixed combination of lisinopril and amlodipine effectively decreases the urinary albumin excretion and BP level as well as improves the endothelial function in diabetic and hypertensive neph-ropathy patients.
Key words: type 2 diabetes, arterial hypertension, microalbuminuria, lisinopril, amlodipine.
1. Bakris GL. Hypertension and nephropathy. Am J Med 2003; 115 (Suppl. 8A): 49–54.
2. Gerstein HC, Mann GF, Yi Q. et al. Albuminuria and risk of cardiovascular events, death and heart failure in diabetic and nondiabetic individuals. JAMA 2001; 286: 421–6.
3. Moser M. The ASCOT trial. J Clin Hypertens (Greenwich) 2005; 7: 748–50.
4. Jamerson K, Weber MA, Bakris GL et al. Benazepril plus amlodipine or hydro-chlorothiazide for hypertension in high-risk patients. N Engl J Med 2008; 359: 2417–28.
5. K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation Classifi-cation Stratification. Am J Kidney Dis 2002; 39 (Suppl. 1): 1–266.
6. Алгоритмы специализированной медицинской помощи больным сахарным диабетом (четвертый выпуск). Под ред. И.И.Дедова, М.В.Шестаковой. М., 2009; с. 104.
7. Celermajer DS, Sorensen KE, Сooch VM. et al. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet 1992; 340: 1111–5.
8. Consensus statement on the definition of orthostatic hypotension, pure autonomic fail-ure and multiple system atrophy. The Consensus Committee of the American Autonomic Society and the American Academy of Neurology (special article). Neurology 1996; 46: 1470.
9. Шестакова М.В. Сахарный диабет и артериальная гипертония.Руководство по артериальной гипертонии. Под ред. Е.И.Чазова, И.Е.Чазовой. М.: Медиа Медика, 2005; с. 415–33.
10. Ольбинская Л.И. Ингибиторы ангиотензинпревращающего фермента и блокаторы рецепторов ангиотензина II при лечении артериальной гипертонии. Руководство по артериальной гипертонии. Под ред. Е.И.Чазова, И.Е.Чазовой. М.: Медиа Медика, 2005; с. 596–615.
11. Диагностика и лечение артериальной гипертензии. Российские рекомендации (четвертый пересмотр). Системные гипертензии 2010; 3: 5–26.
12. Remuzzi G, Macia M, Ruggenenti P. Prevention and treatment of diabetic renal dis-ease in type 2 diabetes: the BENEDICT study. J Am Soc Nephrol 2006; 4 (Suppl. 2): 90–7.
13. Patel A, ADVANCE Collaborative Group, MacMahon S, Chalmers J et al. Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial. Lancet 2007; 370: 829–40.
14. Mogensen CE, Neldan S, Tikkanen I. Randomised controlled trial of dual blockade of renin-angiotensin system in patients with hypertension, microalbuminuria, and non-insulin dependent diabetes: the candesartan and lisinopril microalbuminuria (CALM) study. BMJ 2000; 321: 1440–4.
15. The EUCLID Study Group. Randomised placebo-controlled trial of lisinopril in nor-motensive patients with insulin-dependent diabetes and normoalbuminuria or microalbu-minuria. Lancet 1997; 349 (9068): 1787–92.
16. Viberti G, Wheeldon NM, MicroAlbuminuria Reduction With VALsartan (MAR-VAL) Study Investigators. Microalbuminuria reduction with valsartan in patients with type 2 diabetes mellitus: a blood pressure-independent effect. Circulation 2002; 106 (6): 672–8.
17. Bakris GL, Smith AC, Richardson DJ et al. Impact of an ACE inhibitor and calcium antagonist on microalbuminuria and lipid subfractions in type 2 diabetes: a randomised, multi-centre pilot study. J of Human Hypertens 2002; 16: 185–91.
18. Martinez-Martin FJ, Saiz-Satjes M. Add-on manidipine versus amlodipine in diabetic patients with hypertension and microalbuminuria: the AMANDHA study. Expert Rev Cardiovasc Ther 2008; 6 (10): 1347–55.
19. Zanetti-Elshater F, Pingitore R, Beretta-Piccdi C et al. Calcium antagonists for treat-ment of diabetes-associated hypertension: metabolic and renal effects of amlodipine. Am J Hypertens 1994; 7: 36–45.
20. Shiga Microalbuminuria Reduction Trial (SMART) Group, Uzu T., Sawaguchi M. et al. Impact of renin-angiotensin system inhibition on microalbuminuria in type 2 diabetes: a post hoc analysis of the Shiga Microalbuminuria Reduction Trial (SMART). Hypertens Res 2008; 31 (6): 1171–6.
21. Fogari R, Derosa G, Zoppi A. Effect of telmisartan-amlodipine combination at differ-ent doses on urinary albumin excretion in hypertensive diabetic patients with microalbu-minuria. Am J Hypertens 2007; 20 (4): 417–22.
22. Shigihara T, Sato A, Hayashi K. Effect of combination therapy of angiotensin-converting enzyme inhibitor plus calcium channel blocker on urinary albumin excretion in hypertensive microalbuminuric patients with type II diabetes. Hypertens Res 2000; 23 (3): 219–26.
23. Fogari R, Preti P, Zoppi A et al. Effects of amlodipine fosinopril combination on mi-croalbuminuria in hypertensive type 2 diabetic patients. Am J Hypertens 2002; 15 (12): 1042–9.
24. Zatz R, Meyer TW, Rennke HG et al. Predominance of hemodynamic rather than metabolic factors in the pathogenesis of diabetic glomerulopathy. Proc Natl Acad Sci USA 1985; 82: 5963–67.
25. Reboldi G, Gentile G, Angeli et al. Choice of ACE inhibitor combinations in hyper-tensive patients with type 2 diabetes: update after recent clinical trials. Vasc Health and Risk Management 2009; 5: 411–27.
26. Shultz PJ, Raij L. Effect of amlodipine on mesangial cell proliferation and protein synthesis. Am J Hypertens 1992; 5: 912–4.
27. Toto RD, Tian M, Fakouhi K et al. Effects of calcium channel blockers on proteinuria in patients with diabetic nephropathy. J Clin Hypertens (Greenwich) 2008; 10: 761–9.
28. Bakris GL, Toto RD, McCullough PA et al. Effects of different ACE inhibitor combi-nations on albuminuria: results of the GUARD study. Kidney Int 2008; 73 (11): 1303–9.
29. Bakris GL, Sarafidis PA, Weir MR et al. Renal outcomes with different fixed-dose combination therapies in patients with hypertension at high risk for cardiovascular events (ACCOMPLISH): a prespecified secondary analysis of a randomised controlled trial. Lancet 2010; 375 (9721): 1173–81.
ГОУ ДПО Иркутский государственный институт усовершенствования врачей Минздравсоцразвития РФ;
НУЗ ДКБ на ст. Иркутск-пассажирский ОАО «РЖД»;
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