The 145 references with contexts in paper V. ERMOLENKO M., N. FILATOVA N., A. NIKOLAEV Y., В. ЕРМОЛЕНКО М., Н. ФИЛАТОВА Н., А. НИКОЛАЕВ Ю. (2011) “ИНГИБИЦИЯ РЕНИН-АНГИОТЕНЗИН-АЛЬДОСТЕРОНОВОЙ СИСТЕМЫ И НЕФРОПРОТЕКЦИЯ // INHIBITION OF RENNIN-ANGIOTENSIN-ALDOSTERONE SYSTEM AND NEPHROPROTECTION” / spz:neicon:nefr:y:2011:i:2:p:30-42

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Levitan D, Massry SG, Romoff M, Campese VM. Plasma catecholamines and autonomic nervous system function in patients with early renal insufficiency and hypertension: effect of clonidine. Nephron 1984; 36: 24–29
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    -àëüäîñòåðîíîâîé ñèñòåìû â ïðîãðåññèðîâàíèè õðîíè÷åñêèõ íåôðîïàòèé  ïîääåðæàíèè àðòåðèàëüíîé ãèïåðòåíçèè (ÀÃ) ó íåôðîëîãè÷åñêèõ áîëüíûõ èìåþò çíà÷åíèå ñòåïåíü ãèäðàòàöèè, ñîñòîÿíèå ñèìïàòè÷åñêîé íåðâíîé ñèñòåìû è ìíîãèå äðóãèå ôàêòîðû, îäíàêî âåäóùóþ ðîëü èãðàåò ïîâûøåíèå àêòèâíîñòè ðåíèíàíãèîòåíçèí-àëüäîñòåðîíîâîé ñèñòåìû (ÐÀÀÑ), âûÿâëÿþùååñÿ óæå ïðè íà÷àëüíîé è óìåðåííî âûðàæåííîé ÕÏÍ
    Exact
    [1]
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    . Ïî äàííûì Í.Ë. Ëèôøèö è È.Ì. Êóòûðèíîé [2], àêòèâíîñòü ðåíèíà ïëàçìû ó áîëüíûõ ñ õðîíè÷åñêîé áîëåçíüþ ïî÷åê (ÕÁÏ) 3 ñòàäèè ñ Àà îêàçàëàñü â 3,6 ðàçà âûøå, ÷åì ó çäîðîâûõ, à ó äèàëèçíûõ áîëüíûõ – âûøå â 4,6 ðàçà [2].

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Лифшиц НЛ, Кутырина ИМ. Роль ренин-ангиотензиновой системы в патогенезе артериальной гипертензии при хронической почечной недостаточности. Тер архив 1998; (6): 64–67
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    õðîíè÷åñêèõ íåôðîïàòèé  ïîääåðæàíèè àðòåðèàëüíîé ãèïåðòåíçèè (ÀÃ) ó íåôðîëîãè÷åñêèõ áîëüíûõ èìåþò çíà÷åíèå ñòåïåíü ãèäðàòàöèè, ñîñòîÿíèå ñèìïàòè÷åñêîé íåðâíîé ñèñòåìû è ìíîãèå äðóãèå ôàêòîðû, îäíàêî âåäóùóþ ðîëü èãðàåò ïîâûøåíèå àêòèâíîñòè ðåíèíàíãèîòåíçèí-àëüäîñòåðîíîâîé ñèñòåìû (ÐÀÀÑ), âûÿâëÿþùååñÿ óæå ïðè íà÷àëüíîé è óìåðåííî âûðàæåííîé ÕÏÍ [1]. Ïî äàííûì Í.Ë. Ëèôøèö è È.Ì. Êóòûðèíîé
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    , àêòèâíîñòü ðåíèíà ïëàçìû ó áîëüíûõ ñ õðîíè÷åñêîé áîëåçíüþ ïî÷åê (ÕÁÏ) 3 ñòàäèè ñ Àà îêàçàëàñü â 3,6 ðàçà âûøå, ÷åì ó çäîðîâûõ, à ó äèàëèçíûõ áîëüíûõ – âûøå â 4,6 ðàçà [2]. Êîíöåíòðàöèÿ àëüäîñòåðîíà â ïëàçìå áûëà ïîâûøåíà ñîîòâåòñòâåííî â 3,3 è 5,2 ðàçà, íàðàñòàÿ ïî ìåðå óõóäøåíèÿ ôóíêöèè ïî÷åê [3].

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    Ïî äàííûì Í.Ë. Ëèôøèö è È.Ì. Êóòûðèíîé [2], àêòèâíîñòü ðåíèíà ïëàçìû ó áîëüíûõ ñ õðîíè÷åñêîé áîëåçíüþ ïî÷åê (ÕÁÏ) 3 ñòàäèè ñ Àà îêàçàëàñü â 3,6 ðàçà âûøå, ÷åì ó çäîðîâûõ, à ó äèàëèçíûõ áîëüíûõ – âûøå â 4,6 ðàçà
    Exact
    [2]
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    . Êîíöåíòðàöèÿ àëüäîñòåðîíà â ïëàçìå áûëà ïîâûøåíà ñîîòâåòñòâåííî â 3,3 è 5,2 ðàçà, íàðàñòàÿ ïî ìåðå óõóäøåíèÿ ôóíêöèè ïî÷åê [3]. Ëîêàëüíûå ÐÀÀÑ âíîñÿò îñíîâíîé âêëàä â ïîâðåæäåíèå îðãàíîâ-ìèøåíåé – ïî÷åê, ñåðäöà, ñîñóäîâ, ÖÍÑ, â êîòîðûõ óâåëè÷åííîå ñîäåðæàíèå àíãèîòåíçèíà II (ÀíII) ñîïðîâîæäàåòñÿ äèñôóíêöèåé ýíäîòåëèÿ, îêñèäàòèâíûì ñòðåññîì, âûáðîñîì öèòîêèíîâ ñ ïåðìàíåíòíîé âîñïàëèòåëüíîé ðåàêöè

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Карабаева АЖ, Смирнов АВ, Каюков ИГ, Есаян АМ. Ренин-ангиотензин-альдостероновая система при хронической болезни почек. Нефрология 2006; (3): 43–48
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    Êóòûðèíîé [2], àêòèâíîñòü ðåíèíà ïëàçìû ó áîëüíûõ ñ õðîíè÷åñêîé áîëåçíüþ ïî÷åê (ÕÁÏ) 3 ñòàäèè ñ Àà îêàçàëàñü â 3,6 ðàçà âûøå, ÷åì ó çäîðîâûõ, à ó äèàëèçíûõ áîëüíûõ – âûøå â 4,6 ðàçà [2]. Êîíöåíòðàöèÿ àëüäîñòåðîíà â ïëàçìå áûëà ïîâûøåíà ñîîòâåòñòâåííî â 3,3 è 5,2 ðàçà, íàðàñòàÿ ïî ìåðå óõóäøåíèÿ ôóíêöèè ïî÷åê
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    . Ëîêàëüíûå ÐÀÀÑ âíîñÿò îñíîâíîé âêëàä â ïîâðåæäåíèå îðãàíîâ-ìèøåíåé – ïî÷åê, ñåðäöà, ñîñóäîâ, ÖÍÑ, â êîòîðûõ óâåëè÷åííîå ñîäåðæàíèå àíãèîòåíçèíà II (ÀíII) ñîïðîâîæäàåòñÿ äèñôóíêöèåé ýíäîòåëèÿ, îêñèäàòèâíûì ñòðåññîì, âûáðîñîì öèòîêèíîâ ñ ïåðìàíåíòíîé âîñïàëèòåëüíîé ðåàêöèåé.

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Lonn ЕM, Yusuf S, Jha Р et al. Emerging role of angiotensin–converting enzyme inhibitors in cardiac and vascu1ar protection. Circulation 1994; 90: 2056–2069
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    ÀÃ, ðàçâèòèå àòåðîñêëåðîçà, òðîìáîòè÷åñêèõ îñëîæíåíèé, ïîâðåæäåíèå êàðäèîìèîöèòîâ ñ âîçíèêíîâåíèåì õðîíè÷åñêîé ñåðäå÷íîé íåäîñòàòî÷íîñòè (ÕÑÍ) è ò.ä., à èçáûòî÷íàÿ ñòèìóëÿöèÿ àëüäîñòåðîíîì ìèíåðàëîêîðòèêîèäíûõ ðåöåïòîðîâ ýíäîòåëèàëüíûõ è ãëàäêîìûøå÷íûõ êëåòîê àêòèâèðóåò ýíäîòåëèàëüíóþ äèñôóíêöèþ è âÿëîòåêóùåå âîñïàëåíèå ñîñóäèñòîé ñòåíêè, óòÿæåëÿÿ àòåðîñêëåðîòè÷åñêèé ïðîöåññ è îðãàííóþ ïàòîëîãèþ
    Exact
    [4–9]
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    .  êëóáî÷êàõ ÀíII ÷åðåç èçìåíåíèå òîíóñà ïðèâîäÿùåé è îòâîäÿùåé àðòåðèîë ïîâûøàåò ôèëüòðàöèîííîå äàâëåíèå â êëóáî÷êîâûõ êàïèëëÿðàõ è íàðóøàåò èíòåãðàòèâíîñòü ôèëüòðàöèîííîãî áàðüåðà, óìåíüøàÿ ñèíòåç îòðèöàòåëüíî çàðÿæåííûõ ïðîòåîãëèêàíîâ è èíãèáèðóÿ ýêñïðåññèþ íåôðèíà, à â êàíàëüöàõ ñòèìóëèðóåò ýíäîöèòîç àëüáóìèíà, Åðìîëåíêî Â.

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Dzau V, Berustein K, Celermaier D et al. The relevance of fissure angiotensin–converting enzyme: manifestations in mechanistic and endpoint data. Am J Cardial 2001; 88 [Suppl 1]: 1–20
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    ÀÃ, ðàçâèòèå àòåðîñêëåðîçà, òðîìáîòè÷åñêèõ îñëîæíåíèé, ïîâðåæäåíèå êàðäèîìèîöèòîâ ñ âîçíèêíîâåíèåì õðîíè÷åñêîé ñåðäå÷íîé íåäîñòàòî÷íîñòè (ÕÑÍ) è ò.ä., à èçáûòî÷íàÿ ñòèìóëÿöèÿ àëüäîñòåðîíîì ìèíåðàëîêîðòèêîèäíûõ ðåöåïòîðîâ ýíäîòåëèàëüíûõ è ãëàäêîìûøå÷íûõ êëåòîê àêòèâèðóåò ýíäîòåëèàëüíóþ äèñôóíêöèþ è âÿëîòåêóùåå âîñïàëåíèå ñîñóäèñòîé ñòåíêè, óòÿæåëÿÿ àòåðîñêëåðîòè÷åñêèé ïðîöåññ è îðãàííóþ ïàòîëîãèþ
    Exact
    [4–9]
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    .  êëóáî÷êàõ ÀíII ÷åðåç èçìåíåíèå òîíóñà ïðèâîäÿùåé è îòâîäÿùåé àðòåðèîë ïîâûøàåò ôèëüòðàöèîííîå äàâëåíèå â êëóáî÷êîâûõ êàïèëëÿðàõ è íàðóøàåò èíòåãðàòèâíîñòü ôèëüòðàöèîííîãî áàðüåðà, óìåíüøàÿ ñèíòåç îòðèöàòåëüíî çàðÿæåííûõ ïðîòåîãëèêàíîâ è èíãèáèðóÿ ýêñïðåññèþ íåôðèíà, à â êàíàëüöàõ ñòèìóëèðóåò ýíäîöèòîç àëüáóìèíà, Åðìîëåíêî Â.

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Stier Jr CT, Chander PN, Rocha R et al. Aldosterone as a mediator in cardiovascular injury. Cardiol Rev 2002; 10(2): 97–107
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    ÀÃ, ðàçâèòèå àòåðîñêëåðîçà, òðîìáîòè÷åñêèõ îñëîæíåíèé, ïîâðåæäåíèå êàðäèîìèîöèòîâ ñ âîçíèêíîâåíèåì õðîíè÷åñêîé ñåðäå÷íîé íåäîñòàòî÷íîñòè (ÕÑÍ) è ò.ä., à èçáûòî÷íàÿ ñòèìóëÿöèÿ àëüäîñòåðîíîì ìèíåðàëîêîðòèêîèäíûõ ðåöåïòîðîâ ýíäîòåëèàëüíûõ è ãëàäêîìûøå÷íûõ êëåòîê àêòèâèðóåò ýíäîòåëèàëüíóþ äèñôóíêöèþ è âÿëîòåêóùåå âîñïàëåíèå ñîñóäèñòîé ñòåíêè, óòÿæåëÿÿ àòåðîñêëåðîòè÷åñêèé ïðîöåññ è îðãàííóþ ïàòîëîãèþ
    Exact
    [4–9]
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    .  êëóáî÷êàõ ÀíII ÷åðåç èçìåíåíèå òîíóñà ïðèâîäÿùåé è îòâîäÿùåé àðòåðèîë ïîâûøàåò ôèëüòðàöèîííîå äàâëåíèå â êëóáî÷êîâûõ êàïèëëÿðàõ è íàðóøàåò èíòåãðàòèâíîñòü ôèëüòðàöèîííîãî áàðüåðà, óìåíüøàÿ ñèíòåç îòðèöàòåëüíî çàðÿæåííûõ ïðîòåîãëèêàíîâ è èíãèáèðóÿ ýêñïðåññèþ íåôðèíà, à â êàíàëüöàõ ñòèìóëèðóåò ýíäîöèòîç àëüáóìèíà, Åðìîëåíêî Â.

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Volpe M, Savoia C, De Paolis P et al. The renin– angiotensin system as a risk factor and therapeutic target for cardiovascular and renal disease. J Am Soc Nephrol 2002; 13 [Suppl. 3]: S173–S178
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    ÀÃ, ðàçâèòèå àòåðîñêëåðîçà, òðîìáîòè÷åñêèõ îñëîæíåíèé, ïîâðåæäåíèå êàðäèîìèîöèòîâ ñ âîçíèêíîâåíèåì õðîíè÷åñêîé ñåðäå÷íîé íåäîñòàòî÷íîñòè (ÕÑÍ) è ò.ä., à èçáûòî÷íàÿ ñòèìóëÿöèÿ àëüäîñòåðîíîì ìèíåðàëîêîðòèêîèäíûõ ðåöåïòîðîâ ýíäîòåëèàëüíûõ è ãëàäêîìûøå÷íûõ êëåòîê àêòèâèðóåò ýíäîòåëèàëüíóþ äèñôóíêöèþ è âÿëîòåêóùåå âîñïàëåíèå ñîñóäèñòîé ñòåíêè, óòÿæåëÿÿ àòåðîñêëåðîòè÷åñêèé ïðîöåññ è îðãàííóþ ïàòîëîãèþ
    Exact
    [4–9]
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    .  êëóáî÷êàõ ÀíII ÷åðåç èçìåíåíèå òîíóñà ïðèâîäÿùåé è îòâîäÿùåé àðòåðèîë ïîâûøàåò ôèëüòðàöèîííîå äàâëåíèå â êëóáî÷êîâûõ êàïèëëÿðàõ è íàðóøàåò èíòåãðàòèâíîñòü ôèëüòðàöèîííîãî áàðüåðà, óìåíüøàÿ ñèíòåç îòðèöàòåëüíî çàðÿæåííûõ ïðîòåîãëèêàíîâ è èíãèáèðóÿ ýêñïðåññèþ íåôðèíà, à â êàíàëüöàõ ñòèìóëèðóåò ýíäîöèòîç àëüáóìèíà, Åðìîëåíêî Â.

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Rossi G, Boscaro M, Ronconi V, Funder JW. Aldosterone as a cardiovascular risk factor. Trends Endocrinol Metab 2005; 16: 104–107
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    ÀÃ, ðàçâèòèå àòåðîñêëåðîçà, òðîìáîòè÷åñêèõ îñëîæíåíèé, ïîâðåæäåíèå êàðäèîìèîöèòîâ ñ âîçíèêíîâåíèåì õðîíè÷åñêîé ñåðäå÷íîé íåäîñòàòî÷íîñòè (ÕÑÍ) è ò.ä., à èçáûòî÷íàÿ ñòèìóëÿöèÿ àëüäîñòåðîíîì ìèíåðàëîêîðòèêîèäíûõ ðåöåïòîðîâ ýíäîòåëèàëüíûõ è ãëàäêîìûøå÷íûõ êëåòîê àêòèâèðóåò ýíäîòåëèàëüíóþ äèñôóíêöèþ è âÿëîòåêóùåå âîñïàëåíèå ñîñóäèñòîé ñòåíêè, óòÿæåëÿÿ àòåðîñêëåðîòè÷åñêèé ïðîöåññ è îðãàííóþ ïàòîëîãèþ
    Exact
    [4–9]
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    .  êëóáî÷êàõ ÀíII ÷åðåç èçìåíåíèå òîíóñà ïðèâîäÿùåé è îòâîäÿùåé àðòåðèîë ïîâûøàåò ôèëüòðàöèîííîå äàâëåíèå â êëóáî÷êîâûõ êàïèëëÿðàõ è íàðóøàåò èíòåãðàòèâíîñòü ôèëüòðàöèîííîãî áàðüåðà, óìåíüøàÿ ñèíòåç îòðèöàòåëüíî çàðÿæåííûõ ïðîòåîãëèêàíîâ è èíãèáèðóÿ ýêñïðåññèþ íåôðèíà, à â êàíàëüöàõ ñòèìóëèðóåò ýíäîöèòîç àëüáóìèíà, Åðìîëåíêî Â.

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Ferrario CM, Strawn WB. Role of the renin–angiotensin– aldosterone system and proinflammatory mediators in cardiovascular disease. Am J Cardiol 2006; 98: 121–128
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    ÀÃ, ðàçâèòèå àòåðîñêëåðîçà, òðîìáîòè÷åñêèõ îñëîæíåíèé, ïîâðåæäåíèå êàðäèîìèîöèòîâ ñ âîçíèêíîâåíèåì õðîíè÷åñêîé ñåðäå÷íîé íåäîñòàòî÷íîñòè (ÕÑÍ) è ò.ä., à èçáûòî÷íàÿ ñòèìóëÿöèÿ àëüäîñòåðîíîì ìèíåðàëîêîðòèêîèäíûõ ðåöåïòîðîâ ýíäîòåëèàëüíûõ è ãëàäêîìûøå÷íûõ êëåòîê àêòèâèðóåò ýíäîòåëèàëüíóþ äèñôóíêöèþ è âÿëîòåêóùåå âîñïàëåíèå ñîñóäèñòîé ñòåíêè, óòÿæåëÿÿ àòåðîñêëåðîòè÷åñêèé ïðîöåññ è îðãàííóþ ïàòîëîãèþ
    Exact
    [4–9]
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    .  êëóáî÷êàõ ÀíII ÷åðåç èçìåíåíèå òîíóñà ïðèâîäÿùåé è îòâîäÿùåé àðòåðèîë ïîâûøàåò ôèëüòðàöèîííîå äàâëåíèå â êëóáî÷êîâûõ êàïèëëÿðàõ è íàðóøàåò èíòåãðàòèâíîñòü ôèëüòðàöèîííîãî áàðüåðà, óìåíüøàÿ ñèíòåç îòðèöàòåëüíî çàðÿæåííûõ ïðîòåîãëèêàíîâ è èíãèáèðóÿ ýêñïðåññèþ íåôðèíà, à â êàíàëüöàõ ñòèìóëèðóåò ýíäîöèòîç àëüáóìèíà, Åðìîëåíêî Â.

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Ruster C, Wolf G. Renin–angiotensin–aldosterone system and progression of renal disease. J Am Soc Nephrol 2006; 17: 2985–2991
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    èíãèáèðóÿ ýêñïðåññèþ íåôðèíà, à â êàíàëüöàõ ñòèìóëèðóåò ýíäîöèòîç àëüáóìèíà, Åðìîëåíêî Â.Ì. 125284, Ìîñêâà, 2-é Áîòêèíñêèé ïðîåçä, ä. 5, êîðï. 20; Òåë.: (495) 945-49-01; E-mail: nephrology@mail.ru êîòîðûé, ñ îäíîé ñòîðîíû, àêòèâèðóåò ëîêàëüíóþ ÐÀÀÑ, à ñ äðóãîé – èíäóöèðóåò âûáðîñ õåìîêèíîâ è ïðîâîñïàëèòåëüíûõ öèòîêèíîâ èç êëåòîê òóáóëÿðíîãî ýïèòåëèÿ, èíèöèèðóÿ ðàçâèòèå èíòåðñòèöèàëüíîãî ôèáðîçà
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    . Ñòèìóëèðîâàííûé Àí II òðàíñôîðìèðóþùèé ôàêòîð ðîñòà β (ÒÔÐ-β) ñíèæàåò àêòèâíîñòü ëèçîñîì òóáóëÿðíûõ êëåòîê, ïðîâîöèðóÿ ìèêðîàëüáóìèíóðèþ (ÌÀÓ) [11], ÷òî äàæå ïðè îòíîñèòåëüíî íåâûñîêîì ÀÄ óâåëè÷èâàåò ðèñê âîçíèêíîâåíèÿ ìàññèâíîé ïðîòåèíóðèè è â ïåðñïåêòèâå ñíèæåíèå ñêîðîñòè êëóáî÷êîâîé ôèëüòðàöèè (ÑÊÔ) ñ íåîáðàòèìîé óòðàòîé ôóíêöèè ïî÷åê.

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Russo LM, Osicka TM, Bonnet F et al. Albuminuria in hypertension is linked to altered lysosomal activity and TGF– beta1 expression. Hypertension 2002; 39: 281–286
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    .: (495) 945-49-01; E-mail: nephrology@mail.ru êîòîðûé, ñ îäíîé ñòîðîíû, àêòèâèðóåò ëîêàëüíóþ ÐÀÀÑ, à ñ äðóãîé – èíäóöèðóåò âûáðîñ õåìîêèíîâ è ïðîâîñïàëèòåëüíûõ öèòîêèíîâ èç êëåòîê òóáóëÿðíîãî ýïèòåëèÿ, èíèöèèðóÿ ðàçâèòèå èíòåðñòèöèàëüíîãî ôèáðîçà [10]. Ñòèìóëèðîâàííûé Àí II òðàíñôîðìèðóþùèé ôàêòîð ðîñòà β (ÒÔÐ-β) ñíèæàåò àêòèâíîñòü ëèçîñîì òóáóëÿðíûõ êëåòîê, ïðîâîöèðóÿ ìèêðîàëüáóìèíóðèþ (ÌÀÓ)
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    , ÷òî äàæå ïðè îòíîñèòåëüíî íåâûñîêîì ÀÄ óâåëè÷èâàåò ðèñê âîçíèêíîâåíèÿ ìàññèâíîé ïðîòåèíóðèè è â ïåðñïåêòèâå ñíèæåíèå ñêîðîñòè êëóáî÷êîâîé ôèëüòðàöèè (ÑÊÔ) ñ íåîáðàòèìîé óòðàòîé ôóíêöèè ïî÷åê. Ïîñëåäíÿÿ òðåòü XX â. îçíàìåíîâàëàñü ïîÿâëåíèåì ïðåïàðàòîâ, âëèÿþùèõ íà àêòèâíîñòü ÐÀÀÑ.

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Pals DT, Masucci FD, Sipos F, Denning GS. A specific competitive antagonist of the vascular action of angiotensin II. Cirs Res 1971; 29: 664–672
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    Ïîñëåäíÿÿ òðåòü XX â. îçíàìåíîâàëàñü ïîÿâëåíèåì ïðåïàðàòîâ, âëèÿþùèõ íà àêòèâíîñòü ÐÀÀÑ. Ïåðâûì èõ ïðåäñòàâèòåëåì áûë áëîêàòîð ðåöåïòîðîâ àíãèîòåíçèíà II (ÁÐÀ) ñàðàëàçèí, êîòîðûé âñëåäñòâèå ïåïòèäíîé ïðèðîäû ìîæíî áûëî ââîäèòü òîëüêî ïàðåíòåðàëüíî
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    . Íåïåïòèäíûå ÁÐÀ (ëîçàðòàí) ïîëó÷èëè êëèíè÷åñêîå ðàñïðîñòðàíåíèå ñ 1994 ã. [13], à èíãèáèòîðû àíãèîòåíçèíïðåâðàùàþùåãî ôåðìåíòà (ÈÀÏÔ), ðàçðàáîòàííûå â 1971 ã., øèðîêî èñïîëüçóþòñÿ â êëèíèêå ñ 1978 ã. [14, 15], è óæå ÷åðåç íåñêîëüêî ëåò èõ ïðèìåíåíèÿ ïîÿâèëèñü ïåðâûå ïóáëèêàöèè, êàñàþùèåñÿ âëèÿíèÿ èíãèáèöèè ÐÀÀÑ íà ñîñòîÿíèå ïî÷åê è ñåðäå÷íî-ñîñóäèñòîé ñèñòåìû ó áîëüíûõ ñ äèàáåòè÷åñêèìè è íåäèàáå

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Kang PM, Landau AJ, Eberhardt RT, Fishman WH. Angiotensin II receptor antagonists: a new approach to blockade of the renin–angiotensin system. Am Heart J 1994; 127: 1388–1401
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    Ïåðâûì èõ ïðåäñòàâèòåëåì áûë áëîêàòîð ðåöåïòîðîâ àíãèîòåíçèíà II (ÁÐÀ) ñàðàëàçèí, êîòîðûé âñëåäñòâèå ïåïòèäíîé ïðèðîäû ìîæíî áûëî ââîäèòü òîëüêî ïàðåíòåðàëüíî [12]. Íåïåïòèäíûå ÁÐÀ (ëîçàðòàí) ïîëó÷èëè êëèíè÷åñêîå ðàñïðîñòðàíåíèå ñ 1994 ã.
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    , à èíãèáèòîðû àíãèîòåíçèíïðåâðàùàþùåãî ôåðìåíòà (ÈÀÏÔ), ðàçðàáîòàííûå â 1971 ã., øèðîêî èñïîëüçóþòñÿ â êëèíèêå ñ 1978 ã. [14, 15], è óæå ÷åðåç íåñêîëüêî ëåò èõ ïðèìåíåíèÿ ïîÿâèëèñü ïåðâûå ïóáëèêàöèè, êàñàþùèåñÿ âëèÿíèÿ èíãèáèöèè ÐÀÀÑ íà ñîñòîÿíèå ïî÷åê è ñåðäå÷íî-ñîñóäèñòîé ñèñòåìû ó áîëüíûõ ñ äèàáåòè÷åñêèìè è íåäèàáåòè÷åñêèìè íåôðîïàòèÿìè.

14
Ondetti MA, Williams NJ, Sabo EF et al. Angiotensin– converting enzyme inhibitors from the venom of Bothrops jararaca. Isolation, elucidation of structure, and synthesis. Biochemistry 1971; 10: 4033–4039
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    Íåïåïòèäíûå ÁÐÀ (ëîçàðòàí) ïîëó÷èëè êëèíè÷åñêîå ðàñïðîñòðàíåíèå ñ 1994 ã. [13], à èíãèáèòîðû àíãèîòåíçèíïðåâðàùàþùåãî ôåðìåíòà (ÈÀÏÔ), ðàçðàáîòàííûå â 1971 ã., øèðîêî èñïîëüçóþòñÿ â êëèíèêå ñ 1978 ã.
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    , è óæå ÷åðåç íåñêîëüêî ëåò èõ ïðèìåíåíèÿ ïîÿâèëèñü ïåðâûå ïóáëèêàöèè, êàñàþùèåñÿ âëèÿíèÿ èíãèáèöèè ÐÀÀÑ íà ñîñòîÿíèå ïî÷åê è ñåðäå÷íî-ñîñóäèñòîé ñèñòåìû ó áîëüíûõ ñ äèàáåòè÷åñêèìè è íåäèàáåòè÷åñêèìè íåôðîïàòèÿìè.

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Ondetti MA, Rubin B, Cushman DW. Design of specific inhibitors of angiotensin–converting enzyme: new class of orally active antihypertensive agents. Science 1977; 196: 441–444
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    Íåïåïòèäíûå ÁÐÀ (ëîçàðòàí) ïîëó÷èëè êëèíè÷åñêîå ðàñïðîñòðàíåíèå ñ 1994 ã. [13], à èíãèáèòîðû àíãèîòåíçèíïðåâðàùàþùåãî ôåðìåíòà (ÈÀÏÔ), ðàçðàáîòàííûå â 1971 ã., øèðîêî èñïîëüçóþòñÿ â êëèíèêå ñ 1978 ã.
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    , è óæå ÷åðåç íåñêîëüêî ëåò èõ ïðèìåíåíèÿ ïîÿâèëèñü ïåðâûå ïóáëèêàöèè, êàñàþùèåñÿ âëèÿíèÿ èíãèáèöèè ÐÀÀÑ íà ñîñòîÿíèå ïî÷åê è ñåðäå÷íî-ñîñóäèñòîé ñèñòåìû ó áîëüíûõ ñ äèàáåòè÷åñêèìè è íåäèàáåòè÷åñêèìè íåôðîïàòèÿìè.

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Taguma Y, Kitamomot YK, Futaki G et al. Effect of captopril on heavy proteinuria in azotemic diabetes. N Engl J Med 1985; 313: 1617–1620
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    ÈÀÏÔ), ðàçðàáîòàííûå â 1971 ã., øèðîêî èñïîëüçóþòñÿ â êëèíèêå ñ 1978 ã. [14, 15], è óæå ÷åðåç íåñêîëüêî ëåò èõ ïðèìåíåíèÿ ïîÿâèëèñü ïåðâûå ïóáëèêàöèè, êàñàþùèåñÿ âëèÿíèÿ èíãèáèöèè ÐÀÀÑ íà ñîñòîÿíèå ïî÷åê è ñåðäå÷íî-ñîñóäèñòîé ñèñòåìû ó áîëüíûõ ñ äèàáåòè÷åñêèìè è íåäèàáåòè÷åñêèìè íåôðîïàòèÿìè. Íåôðîïðîòåêòèâíûå ñâîéñòâà èíãèáèòîðîâ àíãèîòåíçèí I-ïðåâðàùàþùåãî ôåðìåíòà  1985 ã. Y. Taguma è ñîàâò.
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    ïðîäåìîíñòðèðîâàëè, ÷òî êàïòîïðèë – ïåðâûé àïðîáèðîâàííûé â êëèíèêå èíãèáèòîð àíãèîòåíçèí I-ïðåâðàùàþùåãî ôåðìåíòà (ÈÀÏÔ), ñîõðàíÿþùèé ñâîå çíà÷åíèå è â íàñòîÿùåå âðåìÿ, â äîçàõ, íå âëèÿþùèõ íà ñèñòåìíîå ÀÄ, ñïîñîáåí âûçâàòü ðåìèññèþ íåôðîòè÷åñêîãî ñèíäðîìà ó àçîòåìè÷åñêèõ áîëüíûõ ñ äèàáåòè÷åñêîé íåôðîïàòèåé.

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Bjorck S, Nyberg G, Mulec H et al. Beneficial effects of angiotensin converting enzyme inhibition on renal function in patients with diabetic nephropathy. BMJ 1986; 293: 471–474
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    Taguma è ñîàâò. [16] ïðîäåìîíñòðèðîâàëè, ÷òî êàïòîïðèë – ïåðâûé àïðîáèðîâàííûé â êëèíèêå èíãèáèòîð àíãèîòåíçèí I-ïðåâðàùàþùåãî ôåðìåíòà (ÈÀÏÔ), ñîõðàíÿþùèé ñâîå çíà÷åíèå è â íàñòîÿùåå âðåìÿ, â äîçàõ, íå âëèÿþùèõ íà ñèñòåìíîå ÀÄ, ñïîñîáåí âûçâàòü ðåìèññèþ íåôðîòè÷åñêîãî ñèíäðîìà ó àçîòåìè÷åñêèõ áîëüíûõ ñ äèàáåòè÷åñêîé íåôðîïàòèåé. S. Bjorck è ñîàâò.
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    ïîêàçàëè, ÷òî ó 13 áîëüíûõ äèàáåòè÷åñêîé íåôðîïàòèåé (ÄÍ) ñ ÕÏÍ è Àà ñïóñòÿ 9 äíåé ïîñëå íàçíà÷åíèÿ ïðåïàðàòà ïî÷å÷íûé êðîâîòîê óâåëè÷èëñÿ ñ 265 äî 302 ìë/ìèí, à ôèëüòðàöèîííàÿ ôðàêöèÿ óìåíüøèëàñü ñ 14,3 äî 12,8%, õîòÿ ÀÄ è ÑÊÔ çà ýòî âðåìÿ ïðàêòè÷åñêè íå èçìåíèëèñü.

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Lewis EJ, Hunsicker LG, Bain RP, Rohde RD. The effect of angiotensin–converting enzyme inhibitors on diabetic nephropathy. The Collaborative Study Group. N Engl J Med
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    è Àà ñïóñòÿ 9 äíåé ïîñëå íàçíà÷åíèÿ ïðåïàðàòà ïî÷å÷íûé êðîâîòîê óâåëè÷èëñÿ ñ 265 äî 302 ìë/ìèí, à ôèëüòðàöèîííàÿ ôðàêöèÿ óìåíüøèëàñü ñ 14,3 äî 12,8%, õîòÿ ÀÄ è ÑÊÔ çà ýòî âðåìÿ ïðàêòè÷åñêè íå èçìåíèëèñü. Òàêèì îáðàçîì, áûëî óñòàíîâëåíî, ÷òî èíãèáèöèÿ àêòèâíîñòè ÐÀÀÑ îêàçûâàåò áëàãîïðèÿòíûé ýôôåêò íà âíóòðèïî÷å÷íóþ ãåìîäèíàìèêó íåçàâèñèìî îò âëèÿíèÿ íà ñèñòåìíîå ÀÄ. Ïî äàííûì E. Lewis è ñîàâò.
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    , ó áîëüíûõ ÑÄ 1 òèïà (n=409) ñ êðåàòèíèíîì ñûâîðîòêè ≥ 2,5 ìã/äë è àëüáóìèíóðèåé > 500 ìã/ñóò íà ôîíå ëå÷åíèÿ êàïòîïðèëîì â òå÷åíèå 3 ëåò ðèñê óäâîåíèÿ êðåàòèíèíà â ñðàâíåíèè ñ ïëàöåáî ñíèçèëñÿ íà 48%, à ðèñê ïåðåâîäà áîëüíûõ íà äèàëèç èëè òðàíñïëàíòàöèþ ïî÷êè, êàê è ðèñê ñìåðòè, óìåíüøèëñÿ íà 50%; íåôðîòè÷åñêàÿ ïðîòåèíóðèÿ ó íåêîòîðûõ ïàöèåíòîâ ñíèçèëàñü äî ñóáêëèíè÷åñêèõ çíà÷åíèé.

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3; 329: 1456–1462 19. Coronel F, Hortal L, Naranjo P et al. Captopril, proteinuria and peritoneal protein leakage in diabetic patients. Nephron 1989; 51: 443
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    Ïîñêîëüêó áîëüíûå ÑÄ ÷àùå âñåãî óìèðàþò îò ñåðäå÷íî-ñîñóäèñòûõ îñëîæíåíèé (ÑÑÎ), áûë ñäåëàí îáîñíîâàííûé âûâîä, ÷òî êàïòîïðèë îáëàäàåò êàê íåôðî-, òàê è êàðäèîïðîòåêòèâíûì ýôôåêòîì. Èìåþòñÿ äàííûå, ÷òî ïðåïàðàò ñïîñîáåí ñíèæàòü íå òîëüêî ïðîòåèíóðèþ, íî è óòå÷êó áåëêà â äèàëèçèðóþùèé ðàñòâîð ó áîëüíûõ ÄÍ íà ïåðèòîíåàëüíîì äèàëèçå
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    . H. Parving è ñîàâò. [20] è M. Ravid è ñîàâò. [21] ïîäòâåðäèëè ñòîéêîñòü íåôðîïðîòåêòèâíîãî ýôôåêòà êàïòîïðèëà è äðóãèõ ÈÀÏÔ ó áîëüíûõ äèàáåòîì 1 è 2 òèïà, à L. Ruilope è ñîàâò. [22] ïðîäåìîíñòðèðîâàëè ñïîñîáíîñòü ïðåïàðàòîâ çàìåäëÿòü ïåðåõîä ÌÀÓ â ñòàäèþ ïðîòåèíóðèè.

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Parving HH, Hommel E, Damkjaer Nielsen M, Giese J. Effect of captopril on blood pressure and kidney function in normotensive insulin dependent diabetics with nephropathy. BMJ 1989; 299: 533–536
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    Ïîñêîëüêó áîëüíûå ÑÄ ÷àùå âñåãî óìèðàþò îò ñåðäå÷íî-ñîñóäèñòûõ îñëîæíåíèé (ÑÑÎ), áûë ñäåëàí îáîñíîâàííûé âûâîä, ÷òî êàïòîïðèë îáëàäàåò êàê íåôðî-, òàê è êàðäèîïðîòåêòèâíûì ýôôåêòîì. Èìåþòñÿ äàííûå, ÷òî ïðåïàðàò ñïîñîáåí ñíèæàòü íå òîëüêî ïðîòåèíóðèþ, íî è óòå÷êó áåëêà â äèàëèçèðóþùèé ðàñòâîð ó áîëüíûõ ÄÍ íà ïåðèòîíåàëüíîì äèàëèçå [19]. H. Parving è ñîàâò.
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    è M. Ravid è ñîàâò. [21] ïîäòâåðäèëè ñòîéêîñòü íåôðîïðîòåêòèâíîãî ýôôåêòà êàïòîïðèëà è äðóãèõ ÈÀÏÔ ó áîëüíûõ äèàáåòîì 1 è 2 òèïà, à L. Ruilope è ñîàâò. [22] ïðîäåìîíñòðèðîâàëè ñïîñîáíîñòü ïðåïàðàòîâ çàìåäëÿòü ïåðåõîä ÌÀÓ â ñòàäèþ ïðîòåèíóðèè.

21
Ravid M, Lang R, Rachmani R, Lishner M. Long-term nephroprotective effect of angiotensin–converting enzyme inhibition in non–insulin–dependint diabetus mellitus. 7-year follow-up study. Arch Intern Med 1996; 156: 286–289
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    Èìåþòñÿ äàííûå, ÷òî ïðåïàðàò ñïîñîáåí ñíèæàòü íå òîëüêî ïðîòåèíóðèþ, íî è óòå÷êó áåëêà â äèàëèçèðóþùèé ðàñòâîð ó áîëüíûõ ÄÍ íà ïåðèòîíåàëüíîì äèàëèçå [19]. H. Parving è ñîàâò. [20] è M. Ravid è ñîàâò.
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    ïîäòâåðäèëè ñòîéêîñòü íåôðîïðîòåêòèâíîãî ýôôåêòà êàïòîïðèëà è äðóãèõ ÈÀÏÔ ó áîëüíûõ äèàáåòîì 1 è 2 òèïà, à L. Ruilope è ñîàâò. [22] ïðîäåìîíñòðèðîâàëè ñïîñîáíîñòü ïðåïàðàòîâ çàìåäëÿòü ïåðåõîä ÌÀÓ â ñòàäèþ ïðîòåèíóðèè.

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Ruilope LM. Renoprotection and rennin–angiotensin system blockade in diabetes mellitus. Am J Hypertens 1997; 10: 325–331
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    Èìåþòñÿ äàííûå, ÷òî ïðåïàðàò ñïîñîáåí ñíèæàòü íå òîëüêî ïðîòåèíóðèþ, íî è óòå÷êó áåëêà â äèàëèçèðóþùèé ðàñòâîð ó áîëüíûõ ÄÍ íà ïåðèòîíåàëüíîì äèàëèçå [19]. H. Parving è ñîàâò. [20] è M. Ravid è ñîàâò. [21] ïîäòâåðäèëè ñòîéêîñòü íåôðîïðîòåêòèâíîãî ýôôåêòà êàïòîïðèëà è äðóãèõ ÈÀÏÔ ó áîëüíûõ äèàáåòîì 1 è 2 òèïà, à L. Ruilope è ñîàâò.
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    ïðîäåìîíñòðèðîâàëè ñïîñîáíîñòü ïðåïàðàòîâ çàìåäëÿòü ïåðåõîä ÌÀÓ â ñòàäèþ ïðîòåèíóðèè. ÌÀÓ íàáëþäàåòñÿ ó 14–48% áîëüíûõ ýññåíöèàëüíîé ãèïåðòåíçèåé (ÝÃ) áåç ïîðàæåíèÿ ïî÷åê [23, 24] è ïðÿìî êîððåëèðóåò ñ âåëè÷èíîé ÀÄ, íî ÷àùå âñåãî ÿâëÿåòñÿ èíäèêàòîðîì ïîðàæåíèÿ òóáóëîãëîìåðóëÿðíîãî àïïàðàòà ïî÷êè.

23
Parving HH, Mogensen CE, Jensen HA, Evrin PE. Increased urinary albumin excretion rate in benign essential hypertension. Lancet 1974; 1: 1190–1192
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    Ravid è ñîàâò. [21] ïîäòâåðäèëè ñòîéêîñòü íåôðîïðîòåêòèâíîãî ýôôåêòà êàïòîïðèëà è äðóãèõ ÈÀÏÔ ó áîëüíûõ äèàáåòîì 1 è 2 òèïà, à L. Ruilope è ñîàâò. [22] ïðîäåìîíñòðèðîâàëè ñïîñîáíîñòü ïðåïàðàòîâ çàìåäëÿòü ïåðåõîä ÌÀÓ â ñòàäèþ ïðîòåèíóðèè. ÌÀÓ íàáëþäàåòñÿ ó 14–48% áîëüíûõ ýññåíöèàëüíîé ãèïåðòåíçèåé (ÝÃ) áåç ïîðàæåíèÿ ïî÷åê
    Exact
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    è ïðÿìî êîððåëèðóåò ñ âåëè÷èíîé ÀÄ, íî ÷àùå âñåãî ÿâëÿåòñÿ èíäèêàòîðîì ïîðàæåíèÿ òóáóëîãëîìåðóëÿðíîãî àïïàðàòà ïî÷êè. Ïðè Ýà ÌÀÓ ñâÿçûâàþò ñ ïîâûøåíèåì ãèäðîñòàòè÷åñêîãî äàâëåíèÿ â êëóáî÷êàõ è ðàçâèòèåì â èòîãå ñòðóêòóðíûõ èçìåíåíèé, ñïîñîáñòâóþùèõ ïàññàæó àëüáóìèíà èç ïëàçìû êðîâè â ìî÷ó [25].

24
Yudkin JS, Forrest RD, Jackson CA. Microalbuminuria predicts cardiovascular disease in non–diabetic subjects. Lancet 1988; 2: 530–533
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    Ravid è ñîàâò. [21] ïîäòâåðäèëè ñòîéêîñòü íåôðîïðîòåêòèâíîãî ýôôåêòà êàïòîïðèëà è äðóãèõ ÈÀÏÔ ó áîëüíûõ äèàáåòîì 1 è 2 òèïà, à L. Ruilope è ñîàâò. [22] ïðîäåìîíñòðèðîâàëè ñïîñîáíîñòü ïðåïàðàòîâ çàìåäëÿòü ïåðåõîä ÌÀÓ â ñòàäèþ ïðîòåèíóðèè. ÌÀÓ íàáëþäàåòñÿ ó 14–48% áîëüíûõ ýññåíöèàëüíîé ãèïåðòåíçèåé (ÝÃ) áåç ïîðàæåíèÿ ïî÷åê
    Exact
    [23, 24]
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    è ïðÿìî êîððåëèðóåò ñ âåëè÷èíîé ÀÄ, íî ÷àùå âñåãî ÿâëÿåòñÿ èíäèêàòîðîì ïîðàæåíèÿ òóáóëîãëîìåðóëÿðíîãî àïïàðàòà ïî÷êè. Ïðè Ýà ÌÀÓ ñâÿçûâàþò ñ ïîâûøåíèåì ãèäðîñòàòè÷åñêîãî äàâëåíèÿ â êëóáî÷êàõ è ðàçâèòèåì â èòîãå ñòðóêòóðíûõ èçìåíåíèé, ñïîñîáñòâóþùèõ ïàññàæó àëüáóìèíà èç ïëàçìû êðîâè â ìî÷ó [25].

25
Ruilope LM, Alcazar JM, Rodicio JL. Renal consequences of arterial hypertension. J Hypertens 1992; 10 [Suppl 7]: S85–S90
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    ÌÀÓ íàáëþäàåòñÿ ó 14–48% áîëüíûõ ýññåíöèàëüíîé ãèïåðòåíçèåé (ÝÃ) áåç ïîðàæåíèÿ ïî÷åê [23, 24] è ïðÿìî êîððåëèðóåò ñ âåëè÷èíîé ÀÄ, íî ÷àùå âñåãî ÿâëÿåòñÿ èíäèêàòîðîì ïîðàæåíèÿ òóáóëîãëîìåðóëÿðíîãî àïïàðàòà ïî÷êè. Ïðè Ýà ÌÀÓ ñâÿçûâàþò ñ ïîâûøåíèåì ãèäðîñòàòè÷åñêîãî äàâëåíèÿ â êëóáî÷êàõ è ðàçâèòèåì â èòîãå ñòðóêòóðíûõ èçìåíåíèé, ñïîñîáñòâóþùèõ ïàññàæó àëüáóìèíà èç ïëàçìû êðîâè â ìî÷ó
    Exact
    [25]
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    . Ó áîëüíûõ ïîñëå îäíîñòîðîííåé íåôðîýêòîìèè è ó äîíîðîâ ïî÷êè ÌÀÓ àññîöèèðîâàíà ñ äèàñòîëè÷åñêèì ÀÄ (ÄÀÄ) è ïîòðåáëåíèåì áåëêà [26, 27], à ïðè íåôðîïàòèÿõ ðàçëè÷íîãî ãåíåçà îòðàæàåò óâåëè÷åíèå ïðîíèöàåìîñòè ãëîìåðóëÿðíîãî ôèëüòðà.

26
Hakim R, Goldszer RC, Brenner BM. Hypertension and proteinuria: Long term sequela and uninephrectomy in humans. Kidney Int 1984; 25: 930–936
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    Ïðè Ýà ÌÀÓ ñâÿçûâàþò ñ ïîâûøåíèåì ãèäðîñòàòè÷åñêîãî äàâëåíèÿ â êëóáî÷êàõ è ðàçâèòèåì â èòîãå ñòðóêòóðíûõ èçìåíåíèé, ñïîñîáñòâóþùèõ ïàññàæó àëüáóìèíà èç ïëàçìû êðîâè â ìî÷ó [25]. Ó áîëüíûõ ïîñëå îäíîñòîðîííåé íåôðîýêòîìèè è ó äîíîðîâ ïî÷êè ÌÀÓ àññîöèèðîâàíà ñ äèàñòîëè÷åñêèì ÀÄ (ÄÀÄ) è ïîòðåáëåíèåì áåëêà
    Exact
    [26, 27]
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    , à ïðè íåôðîïàòèÿõ ðàçëè÷íîãî ãåíåçà îòðàæàåò óâåëè÷åíèå ïðîíèöàåìîñòè ãëîìåðóëÿðíîãî ôèëüòðà. Ïðè ãèïåðòåíçèâíîé íåôðîïàòèè âûÿâëåíà êîððåëÿöèÿ ìåæäó ÌÀÓ è ýêñêðåòèðóåìûìè ñ ìî÷îé áèîìàðêåðàìè – PAI1, TGF-β, VÅGF, êîëëàãåíîì IV òèïà, îòðàæàþùèìè óñèëåíèå ïðîöåññîâ ôèáðîãåíåçà â ïî÷êå.

27
Coppo R, Amore A, Roccatello D et al. Microalbuminuria in single kidney patients: relationship with protein intake. Clin Nephrol 1988; 29 (5): 219–228
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    Ïðè Ýà ÌÀÓ ñâÿçûâàþò ñ ïîâûøåíèåì ãèäðîñòàòè÷åñêîãî äàâëåíèÿ â êëóáî÷êàõ è ðàçâèòèåì â èòîãå ñòðóêòóðíûõ èçìåíåíèé, ñïîñîáñòâóþùèõ ïàññàæó àëüáóìèíà èç ïëàçìû êðîâè â ìî÷ó [25]. Ó áîëüíûõ ïîñëå îäíîñòîðîííåé íåôðîýêòîìèè è ó äîíîðîâ ïî÷êè ÌÀÓ àññîöèèðîâàíà ñ äèàñòîëè÷åñêèì ÀÄ (ÄÀÄ) è ïîòðåáëåíèåì áåëêà
    Exact
    [26, 27]
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    , à ïðè íåôðîïàòèÿõ ðàçëè÷íîãî ãåíåçà îòðàæàåò óâåëè÷åíèå ïðîíèöàåìîñòè ãëîìåðóëÿðíîãî ôèëüòðà. Ïðè ãèïåðòåíçèâíîé íåôðîïàòèè âûÿâëåíà êîððåëÿöèÿ ìåæäó ÌÀÓ è ýêñêðåòèðóåìûìè ñ ìî÷îé áèîìàðêåðàìè – PAI1, TGF-β, VÅGF, êîëëàãåíîì IV òèïà, îòðàæàþùèìè óñèëåíèå ïðîöåññîâ ôèáðîãåíåçà â ïî÷êå.

28
Нанчикеева МЛ, Козловская ЛВ, Фомин ВВ и др. Эндотелиальная дисфункция и ремоделирование внутрипочечных сосудов как основа формирования гипертонической нефропатии. Ультразвуковая и функциональная диагностика 2009; (5): 84–94
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    Ïðè ãèïåðòåíçèâíîé íåôðîïàòèè âûÿâëåíà êîððåëÿöèÿ ìåæäó ÌÀÓ è ýêñêðåòèðóåìûìè ñ ìî÷îé áèîìàðêåðàìè – PAI1, TGF-β, VÅGF, êîëëàãåíîì IV òèïà, îòðàæàþùèìè óñèëåíèå ïðîöåññîâ ôèáðîãåíåçà â ïî÷êå. Ó áîëüíûõ, ó êîòîðûõ íà ôîíå ïðèåìà ÈÀÏÔ óäàâàëîñü ïîääåðæèâàòü öåëåâûå çíà÷åíèÿ ÀÄ, íå ðàçâèâàëàñü èëè èñ÷åçàëà ÌÀÓ, íå ïðîèñõîäèëî ïðîãðåññèðîâàíèå íåôðîïàòèè è ãèïåðòðîôèè ìèîêàðäà
    Exact
    [28]
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    .  èññëåäîâàíèè BENEDICT (The BErgamo NEphrologic DIabetes Complications Trial) ó áîëüíûõ Àà ëå÷åíèå ÈÀÏÔ è ñíèæåíèå ÀÄ íåçàâèñèìî ïðåäóïðåæäàëè ðàçâèòèå ÌÀÓ [29].  ïîñëåäíèå ãîäû ÌÀÓ ðàññìàòðèâàþò â êà÷åñòâå èíòåãðàëüíîãî ìàðêåðà íå òîëüêî ëîêàëüíîïî÷å÷íîé, íî è ñèñòåìíîé äèñôóíêöèè ýíäîòåëèÿ, ôîðìèðóþùåéñÿ íà ôîíå óâåëè÷åíèÿ ìàññû òåëà, íàðóøåíèÿ îáìåíà ìî÷åâîé êèñëîòû, ãèïåðãîìîöèñòåèíåìèè, ã

29
Ruggenenti P, Perna A, Ganeva M et al. Impact of blood pressure control and angiotensin–converting enzyme inhibitor therapy on new–onset microalbuminuria in type 2 diabetes: a post hoc analysis of the BENEDICT trial. J Am Soc Nephrol 2006; 17: 3472–3481
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    Ó áîëüíûõ, ó êîòîðûõ íà ôîíå ïðèåìà ÈÀÏÔ óäàâàëîñü ïîääåðæèâàòü öåëåâûå çíà÷åíèÿ ÀÄ, íå ðàçâèâàëàñü èëè èñ÷åçàëà ÌÀÓ, íå ïðîèñõîäèëî ïðîãðåññèðîâàíèå íåôðîïàòèè è ãèïåðòðîôèè ìèîêàðäà [28].  èññëåäîâàíèè BENEDICT (The BErgamo NEphrologic DIabetes Complications Trial) ó áîëüíûõ Àà ëå÷åíèå ÈÀÏÔ è ñíèæåíèå ÀÄ íåçàâèñèìî ïðåäóïðåæäàëè ðàçâèòèå ÌÀÓ
    Exact
    [29]
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    .  ïîñëåäíèå ãîäû ÌÀÓ ðàññìàòðèâàþò â êà÷åñòâå èíòåãðàëüíîãî ìàðêåðà íå òîëüêî ëîêàëüíîïî÷å÷íîé, íî è ñèñòåìíîé äèñôóíêöèè ýíäîòåëèÿ, ôîðìèðóþùåéñÿ íà ôîíå óâåëè÷åíèÿ ìàññû òåëà, íàðóøåíèÿ îáìåíà ìî÷åâîé êèñëîòû, ãèïåðãîìîöèñòåèíåìèè, ãèïåðïðîäóêöèè àñèììåòðè÷íîãî äèìåòèëàðãèíèíà.

30
Shinosaki T, Miyai I, Nomura Y et al. Mechanisms underlying the ameliorative property of lisinopril in progressive mesangioproliferative nephritis. Nephron 2002; 91 (4): 719–729
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    Àíòèïðîòåèíóðè÷åñêèé ýôôåêò ÈÀÏÔ îáóñëîâëåí ñíèæåíèåì ñèñòåìíîãî ÀÄ è äàâëåíèÿ â êëóáî÷êîâûõ êàïèëëÿðàõ, ñïîñîáíîñòüþ óëó÷øàòü êðîâîñíàáæåíèå ïî÷å÷íîãî èíòåðñòèöèÿ, ïîäàâëÿòü ïðîäóêöèþ âîñïàëèòåëüíûõ öèòîêèíîâ, ôàêòîðîâ òðàíñêðèïöèè è ôèáðîãåíåçà. Ïî äàííûì T. Shinosaki è ñîàâò.
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    , ëèçèíîïðèë ñïîñîáñòâóåò ñîõðàíåíèþ îòðèöàòåëüíîãî çàðÿäà ãëîìåðóëÿðíîé áàçàëüíîé ìåìáðàíû è óìåíüøàåò ñòåïåíü ïîâðåæäåíèÿ ïîäîöèòîâ ó æèâîòíûõ ñ Th1-íåôðèòîì, à ó áîëüíûõ IgA-íåôðîïàòèåé ñíèæàåò â êðîâè êîíöåíòðàöèþ bcl-2 – ôàêòîðà, ñâÿçàííîãî ñ àêòèâàöèåé àïîïòîçà [31].

31
Buemi M, Allegra A, Corica F et al. Effects of lisinopril administration on blood bcl–2 concentrations in patients with immunoglobulin A nephropathy. Clin Pharmacol Ther 1999; 65 (6): 649–652
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    Shinosaki è ñîàâò. [30], ëèçèíîïðèë ñïîñîáñòâóåò ñîõðàíåíèþ îòðèöàòåëüíîãî çàðÿäà ãëîìåðóëÿðíîé áàçàëüíîé ìåìáðàíû è óìåíüøàåò ñòåïåíü ïîâðåæäåíèÿ ïîäîöèòîâ ó æèâîòíûõ ñ Th1-íåôðèòîì, à ó áîëüíûõ IgA-íåôðîïàòèåé ñíèæàåò â êðîâè êîíöåíòðàöèþ bcl-2 – ôàêòîðà, ñâÿçàííîãî ñ àêòèâàöèåé àïîïòîçà
    Exact
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    . Ó 530 áîëüíûõ ÑÄ òèïà 1 ñ íîðìàëüíûì ÀÄ ëèçèíîïðèë äîñòîâåðíî ñíèæàë àëüáóìèíóðèþ [32]. Ñîãëàñíî E. Morelli è ñîàâò. [33], ýíàëàïðèë è äðóãèå ÈÀÏÔ âëèÿþò íà ñâîéñòâà ãëîìåðóëÿðíîé áàçàëüíîé ìåìáðàíû, èíäóöèðóÿ â íåé îáðàçîâàíèå ïîð ñ íåáîëüøèì äèàìåòðîì, íå ïðîíèöàåìûõ äëÿ ïëàçìåííûõ áåëêîâ.

32
The EUCLID Study Group. Randomised placebo– controlled trial of lisinopril in normotensive patients with insulin– dependent diabetes and normoalbuminuria or microalbuminuria. Lancet 1997; 349: 1787–1792
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    Shinosaki è ñîàâò. [30], ëèçèíîïðèë ñïîñîáñòâóåò ñîõðàíåíèþ îòðèöàòåëüíîãî çàðÿäà ãëîìåðóëÿðíîé áàçàëüíîé ìåìáðàíû è óìåíüøàåò ñòåïåíü ïîâðåæäåíèÿ ïîäîöèòîâ ó æèâîòíûõ ñ Th1-íåôðèòîì, à ó áîëüíûõ IgA-íåôðîïàòèåé ñíèæàåò â êðîâè êîíöåíòðàöèþ bcl-2 – ôàêòîðà, ñâÿçàííîãî ñ àêòèâàöèåé àïîïòîçà [31]. Ó 530 áîëüíûõ ÑÄ òèïà 1 ñ íîðìàëüíûì ÀÄ ëèçèíîïðèë äîñòîâåðíî ñíèæàë àëüáóìèíóðèþ
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    . Ñîãëàñíî E. Morelli è ñîàâò. [33], ýíàëàïðèë è äðóãèå ÈÀÏÔ âëèÿþò íà ñâîéñòâà ãëîìåðóëÿðíîé áàçàëüíîé ìåìáðàíû, èíäóöèðóÿ â íåé îáðàçîâàíèå ïîð ñ íåáîëüøèì äèàìåòðîì, íå ïðîíèöàåìûõ äëÿ ïëàçìåííûõ áåëêîâ.

33
Morelli E, Loon N, Meye TW et al. Effects of converting– enzyme inhibition on barrier function in diabetic glomerulopathy. Diabetes 1990; 39 (1): 76–82
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    . [30], ëèçèíîïðèë ñïîñîáñòâóåò ñîõðàíåíèþ îòðèöàòåëüíîãî çàðÿäà ãëîìåðóëÿðíîé áàçàëüíîé ìåìáðàíû è óìåíüøàåò ñòåïåíü ïîâðåæäåíèÿ ïîäîöèòîâ ó æèâîòíûõ ñ Th1-íåôðèòîì, à ó áîëüíûõ IgA-íåôðîïàòèåé ñíèæàåò â êðîâè êîíöåíòðàöèþ bcl-2 – ôàêòîðà, ñâÿçàííîãî ñ àêòèâàöèåé àïîïòîçà [31]. Ó 530 áîëüíûõ ÑÄ òèïà 1 ñ íîðìàëüíûì ÀÄ ëèçèíîïðèë äîñòîâåðíî ñíèæàë àëüáóìèíóðèþ [32]. Ñîãëàñíî E. Morelli è ñîàâò.
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    [33]
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    , ýíàëàïðèë è äðóãèå ÈÀÏÔ âëèÿþò íà ñâîéñòâà ãëîìåðóëÿðíîé áàçàëüíîé ìåìáðàíû, èíäóöèðóÿ â íåé îáðàçîâàíèå ïîð ñ íåáîëüøèì äèàìåòðîì, íå ïðîíèöàåìûõ äëÿ ïëàçìåííûõ áåëêîâ. Àíàëîãè÷íî âëèÿþò íà ïðîòåèíóðèþ è ÁÐÀ (âàëñàðòàí), êîòîðûé ïîâûøàåò ñåëåêòèâíîñòü ïðîòåèíóðèè è óìåíüøàåò ýêñêðåöèþ òðàíñôåððèíà, îêàçûâàþùåãî òîêñè÷åñêîå äåéñòâèå íà ýïèòåëèé ïðîêñèìàëüíûõ êàíàëüöåâ, ïðîâîöèðóÿ ðàçâèòèå èíòåðñ

34
Медведева ТЮ. Влияние препаратов, блокирующих ренин-ангиотензиновую систему, на прогрессирование почечной недостаточности в клинике и эксперименте. Автореф. дис. ... канд. мед. наук. М., 2001
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    Àíàëîãè÷íî âëèÿþò íà ïðîòåèíóðèþ è ÁÐÀ (âàëñàðòàí), êîòîðûé ïîâûøàåò ñåëåêòèâíîñòü ïðîòåèíóðèè è óìåíüøàåò ýêñêðåöèþ òðàíñôåððèíà, îêàçûâàþùåãî òîêñè÷åñêîå äåéñòâèå íà ýïèòåëèé ïðîêñèìàëüíûõ êàíàëüöåâ, ïðîâîöèðóÿ ðàçâèòèå èíòåðñòèöèàëüíîãî ñêëåðîçà
    Exact
    [34]
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    . ÌÀÓ è ïðîòåèíóðèÿ íå òîëüêî óñêîðÿþò ïðîãðåññèðîâàíèå äèñôóíêöèè ïî÷åê, íî è âëèÿþò íà ðàçâèòèå ñåðäå÷íî–ñîñóäèñòûõ îñëîæíåíèé ó íåôðîëîãè÷åñêèõ áîëüíûõ.  èññëåäîâàíèè HOPE (The Heart Outcomes Prevention Evaluation) ïðèñóòñòâèå ó áîëüíûõ c Àà ÌÀÓ âäâîå óâåëè÷èâàëî ÷àñòîòó ÑÑÎ.

35
Gerstein HC, Mann JF, Yi Q et al. Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals. JAMA 2001; 286: 421–426
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     èññëåäîâàíèè HOPE (The Heart Outcomes Prevention Evaluation) ïðèñóòñòâèå ó áîëüíûõ c Àà ÌÀÓ âäâîå óâåëè÷èâàëî ÷àñòîòó ÑÑÎ. Áûëî ðàññ÷èòàíî, ÷òî óâåëè÷åíèå ýêñêðåöèè àëüáóìèíà ñ ìî÷îé íà êàæäûå 0,4 ìã/ìîëü êðåàòèíèíà ïîâûøàåò ÷àñòîòó ÑÑÎ íà 5,9%, ëåòàëüíîñòü – íà 6,8%, ÷èñëî ãîñïèòàëèçàöèé â ñâÿçè ñ ÕÑÍ – íà 10,6%
    Exact
    [35]
    Suffix
    . Ïðîãíîñòè÷åñêè íåáëàãîïðèÿòíîé áûëà è ñàìà ïî÷å÷íàÿ äèñôóíêöèÿ. Ïîñëåäóþùèé (post hoc) àíàëèç ïîêàçàë, ÷òî äàæå óìåðåííî âûðàæåííàÿ ïî÷å÷íàÿ íåäîñòàòî÷íîñòü ïî÷òè â 2 ðàçà ïîâûøàëà ðèñê (11,4 ïðîòèâ 6,6%) íåáëàãîïðèÿòíûõ ïåðâè÷íûõ èñõîäîâ (ñåðäå÷íî–ñîñóäèñòàÿ ñìåðòü, èíôàðêò ìèîêàðäà, èíñóëüò) ïî ñðàâíåíèþ ñ áîëüíûìè áåç íàðóøåíèÿ ôóíêöèè ïî÷åê.

36
Mann JF, Gerstein HC, Pogue J et al. Renal insufficiency as a predictor of cardiovascular outcomes and the impact of ramipril: the HOPE randomized trial. Ann intern Med 2001; 134: 629–636
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    Çà 4,5 ãîäà íàáëþäåíèÿ ðèñê ëåòàëüíûõ èñõîäîâ îêàçàëñÿ íà 43% âûøå ó áîëüíûõ ñ êðåàòèíèíîì ñûâîðîòêè îò 1,4 äî 2,3 ìã%, ÷åì ó ïàöèåíòîâ áåç ïî÷å÷íîé íåäîñòàòî÷íîñòè. Ðàìèïðèë â ñóáìàêñèìàëüíûõ äîçàõ óëó÷øàë ïðîãíîç ó ïàöèåíòîâ îáåèõ ãðóïï
    Exact
    [36]
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    , íî â íåáîëüøèõ äîçàõ (1,25 ìã/ñóò) íå îêàçûâàë ýôôåêòà íà ñåðäå÷íî–ñîñóäèñòûå è ïî÷å÷íûå èñõîäû ó 2443 áîëüíûõ ÑÄ òèïà 2, íåñìîòðÿ íà íåêîòîðîå ñíèæåíèå ñèñòåìíîãî ÀÄ è àëüáóìèíóðèè [37]. Àíàëèç ðåçóëüòàòîâ èññëåäîâàíèÿ REIN (Ramipril Efficacy in Nephropathy) ïîçâîëèë àâòîðàì ñäåëàòü âûâîä, ÷òî ðàìèïðèë â ìàêñèìàëüíîé ñòåïåíè (â 100%) ïðåäóïðåæäàåò ðàçâèòèå ÒÏÍ ó áîëüíûõ ñ èçíà÷àëüíî íèçêîé ÑÊÔ,

37
Marre M, Lievre M, Chatellier G et al. Effects of low dose ramipril on cardiovascular and renal outcomes in patients with type 2 diabetes and raised excretion of urinary albumin: randomised, double blind, placebo controlled trial (the DIABHYCAR study). BMJ 2004; 328: 495–498
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    Ðàìèïðèë â ñóáìàêñèìàëüíûõ äîçàõ óëó÷øàë ïðîãíîç ó ïàöèåíòîâ îáåèõ ãðóïï [36], íî â íåáîëüøèõ äîçàõ (1,25 ìã/ñóò) íå îêàçûâàë ýôôåêòà íà ñåðäå÷íî–ñîñóäèñòûå è ïî÷å÷íûå èñõîäû ó 2443 áîëüíûõ ÑÄ òèïà 2, íåñìîòðÿ íà íåêîòîðîå ñíèæåíèå ñèñòåìíîãî ÀÄ è àëüáóìèíóðèè
    Exact
    [37]
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    . Àíàëèç ðåçóëüòàòîâ èññëåäîâàíèÿ REIN (Ramipril Efficacy in Nephropathy) ïîçâîëèë àâòîðàì ñäåëàòü âûâîä, ÷òî ðàìèïðèë â ìàêñèìàëüíîé ñòåïåíè (â 100%) ïðåäóïðåæäàåò ðàçâèòèå ÒÏÍ ó áîëüíûõ ñ èçíà÷àëüíî íèçêîé ÑÊÔ, îäíàêî ïîëíîöåííàÿ íåôðîïðîòåêöèÿ íàáëþäàåòñÿ òîëüêî ïðè ðàííåì è ïðîäîëæèòåëüíîì ëå÷åíèè [38].

38
Ruggenenti P, Perna A, Remuzzi G. ACE inhibitors to prevent End-stage Renal Disease: when to start and why possibly never stop: a post–hoc analysis of the REIN trial results. J Am Soc Nephrol 2001; 12: 2832–2837
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    Àíàëèç ðåçóëüòàòîâ èññëåäîâàíèÿ REIN (Ramipril Efficacy in Nephropathy) ïîçâîëèë àâòîðàì ñäåëàòü âûâîä, ÷òî ðàìèïðèë â ìàêñèìàëüíîé ñòåïåíè (â 100%) ïðåäóïðåæäàåò ðàçâèòèå ÒÏÍ ó áîëüíûõ ñ èçíà÷àëüíî íèçêîé ÑÊÔ, îäíàêî ïîëíîöåííàÿ íåôðîïðîòåêöèÿ íàáëþäàåòñÿ òîëüêî ïðè ðàííåì è ïðîäîëæèòåëüíîì ëå÷åíèè
    Exact
    [38]
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    . Íåôðîïðîòåêòèâíûå ñâîéñòâà ÁÐÀ Íåôðîïðîòåêòèâíûå ýôôåêòû ÁÐÀ ïðè ÄÍ ïðîñëåæåíû â 4 èññëåäîâàíèÿõ.  èññëåäîâàíèè IRMA (Irbersartan Microalbuminuria) áîëüíûì ÑÄ òèïà 2 ñ Àà íàçíà÷àëè èðáåñàðòàí â äîçå 150 èëè 300 ìã/ ñóò èëè ñòàíäàðòíóþ (áåç áëîêàòîðîâ ÐÀÀÑ) àíòèãèïåðòåíçèâíóþ òåðàïèþ.

39
Lewis E, Hunsicker L, Clarke W et al. Renoprotective effect of the angiotensin–receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001; 345: 851–860
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    Èðáåñàðòàí äîçîçàâèñèìî ñíèæàë ó áîëüíûõ ðèñê ðàçâèòèÿ ÄÍ è èíäóöèðîâàë ïåðåõîä ÌÀÓ â íîðìîàëüáóìèíóðèþ, çàìåäëÿÿ ïðîãðåññèðîâàíèå è âåðîÿòíîñòü ñìåðòåëüíûõ èñõîäîâ, ïðè÷åì ÀÄ ó áîëüíûõ ñðàâíèâàåìûõ ãðóïï áûëî ïðèìåðíî îäèíàêîâûì, ñâèäåòåëüñòâóÿ, ÷òî ýôôåêòû èðáåñàðòàíà îïîñðåäóþòñÿ íå òîëüêî ÷åðåç êîððåêöèþ ÀÄ
    Exact
    [39, 40]
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    . Ó áîëüíûõ ÑÄ (n=16600) 3 ìåñ ëå÷åíèå èðáåñàðòàíîì íà 15% óìåíüøèëî ÷èñëî ïàöèåíòîâ ñ ìèêðîàëüáóìèíóðèåé [41], à òåëìèñàðòàí ïðè ëå÷åíèè àíàëîãè÷íîãî êîíòèíãåíòà ïðåäóïðåæäàë ïåðåõîä ÌÀÓ â ñòàäèþ ïðîòåèíóðèè [42].

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Parving HH, Lehnert H, Brochner–Mortensen J et al. Irbesartan in patients with type 2 diabetes and microalbuminuria study group. The effect of Irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med 2001; 345: 870–878.
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    Èðáåñàðòàí äîçîçàâèñèìî ñíèæàë ó áîëüíûõ ðèñê ðàçâèòèÿ ÄÍ è èíäóöèðîâàë ïåðåõîä ÌÀÓ â íîðìîàëüáóìèíóðèþ, çàìåäëÿÿ ïðîãðåññèðîâàíèå è âåðîÿòíîñòü ñìåðòåëüíûõ èñõîäîâ, ïðè÷åì ÀÄ ó áîëüíûõ ñðàâíèâàåìûõ ãðóïï áûëî ïðèìåðíî îäèíàêîâûì, ñâèäåòåëüñòâóÿ, ÷òî ýôôåêòû èðáåñàðòàíà îïîñðåäóþòñÿ íå òîëüêî ÷åðåç êîððåêöèþ ÀÄ
    Exact
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    . Ó áîëüíûõ ÑÄ (n=16600) 3 ìåñ ëå÷åíèå èðáåñàðòàíîì íà 15% óìåíüøèëî ÷èñëî ïàöèåíòîâ ñ ìèêðîàëüáóìèíóðèåé [41], à òåëìèñàðòàí ïðè ëå÷åíèè àíàëîãè÷íîãî êîíòèíãåíòà ïðåäóïðåæäàë ïåðåõîä ÌÀÓ â ñòàäèþ ïðîòåèíóðèè [42].

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Bramlage P, Pittrow D, Kirch W. The effect of irbesartan in reducing cardiovascular risk in hypertensive type 2 diabetic patients: an observational study in 16,600 patients in primary care. Curr Med Res Opin 2004; 20: 1625–1631
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    ó áîëüíûõ ðèñê ðàçâèòèÿ ÄÍ è èíäóöèðîâàë ïåðåõîä ÌÀÓ â íîðìîàëüáóìèíóðèþ, çàìåäëÿÿ ïðîãðåññèðîâàíèå è âåðîÿòíîñòü ñìåðòåëüíûõ èñõîäîâ, ïðè÷åì ÀÄ ó áîëüíûõ ñðàâíèâàåìûõ ãðóïï áûëî ïðèìåðíî îäèíàêîâûì, ñâèäåòåëüñòâóÿ, ÷òî ýôôåêòû èðáåñàðòàíà îïîñðåäóþòñÿ íå òîëüêî ÷åðåç êîððåêöèþ ÀÄ [39, 40]. Ó áîëüíûõ ÑÄ (n=16600) 3 ìåñ ëå÷åíèå èðáåñàðòàíîì íà 15% óìåíüøèëî ÷èñëî ïàöèåíòîâ ñ ìèêðîàëüáóìèíóðèåé
    Exact
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    , à òåëìèñàðòàí ïðè ëå÷åíèè àíàëîãè÷íîãî êîíòèíãåíòà ïðåäóïðåæäàë ïåðåõîä ÌÀÓ â ñòàäèþ ïðîòåèíóðèè [42].  èññëåäîâàíèè RENAAL (Reduction of Endpoints in non–insulin dependent diabetes with Angoitensin II Antagonist Losartan) ó 1513 áîëüíûõ ÑÄ òèïà 2 ëîçàðòàí â äîçå 50–100 ìã/ñóò â òå÷åíèå 52 íåä â ñðàâíåíèè ñ ïëàöåáî ñíèæàë íà 25% ðèñê óäâîåíèÿ êðåàòèíèíà ñûâîðîòêè è íà 28% – ðèñê ðàçâèòèÿ òå

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Makino H, Haneda M, Babazono T et al. Prevention of transition from incipient to overt nephropathy with telmisartan in patients with type 2 diabetes. Diabetes Care 2007; 30: 1577– 1578
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    Ó áîëüíûõ ÑÄ (n=16600) 3 ìåñ ëå÷åíèå èðáåñàðòàíîì íà 15% óìåíüøèëî ÷èñëî ïàöèåíòîâ ñ ìèêðîàëüáóìèíóðèåé [41], à òåëìèñàðòàí ïðè ëå÷åíèè àíàëîãè÷íîãî êîíòèíãåíòà ïðåäóïðåæäàë ïåðåõîä ÌÀÓ â ñòàäèþ ïðîòåèíóðèè
    Exact
    [42]
    Suffix
    .  èññëåäîâàíèè RENAAL (Reduction of Endpoints in non–insulin dependent diabetes with Angoitensin II Antagonist Losartan) ó 1513 áîëüíûõ ÑÄ òèïà 2 ëîçàðòàí â äîçå 50–100 ìã/ñóò â òå÷åíèå 52 íåä â ñðàâíåíèè ñ ïëàöåáî ñíèæàë íà 25% ðèñê óäâîåíèÿ êðåàòèíèíà ñûâîðîòêè è íà 28% – ðèñê ðàçâèòèÿ òåðìèíàëüíîé óðåìèè [43].

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Brenner BM, Cooper ME, de Zeeuw D et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001; 345: 861–869
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     èññëåäîâàíèè RENAAL (Reduction of Endpoints in non–insulin dependent diabetes with Angoitensin II Antagonist Losartan) ó 1513 áîëüíûõ ÑÄ òèïà 2 ëîçàðòàí â äîçå 50–100 ìã/ñóò â òå÷åíèå 52 íåä â ñðàâíåíèè ñ ïëàöåáî ñíèæàë íà 25% ðèñê óäâîåíèÿ êðåàòèíèíà ñûâîðîòêè è íà 28% – ðèñê ðàçâèòèÿ òåðìèíàëüíîé óðåìèè
    Exact
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    . Íà çàìåäëåíèå ïðîãðåññèðîâàíèÿ âëèÿëè íå òîëüêî ñòåïåíü ñíèæåíèÿ, íî è âåëè÷èíà îñòàòî÷íîé ïðîòåèíóðèè [44].  ìåíåå ìàñøòàáíîì (n=332) èññëåäîâàíèè MARVAL (Microalbuminuria Reduction with Valsartan in patients with type 2 diabetes mellitus) ëå÷åíèå âàëñàðòàíîì (80 ìã/ñóò) â òå÷åíèå 24 íåä ñíèæàëî àëüáóìèíóðèþ íà 44% íåçàâèñèìî îò âåëè÷èíû ÀÄ è òîëüêî íà 8% – â ãðóïïå àìëîäèïèíà.

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Zeeuw D, Remuzzi G, Parving HH et al. Proteinuria, a target for renoprotection in patients with type 2 diabetic nephropathy: Lessons from RENAAL. Kidney Int 2004; 65: 2309– 2320
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    (Reduction of Endpoints in non–insulin dependent diabetes with Angoitensin II Antagonist Losartan) ó 1513 áîëüíûõ ÑÄ òèïà 2 ëîçàðòàí â äîçå 50–100 ìã/ñóò â òå÷åíèå 52 íåä â ñðàâíåíèè ñ ïëàöåáî ñíèæàë íà 25% ðèñê óäâîåíèÿ êðåàòèíèíà ñûâîðîòêè è íà 28% – ðèñê ðàçâèòèÿ òåðìèíàëüíîé óðåìèè [43]. Íà çàìåäëåíèå ïðîãðåññèðîâàíèÿ âëèÿëè íå òîëüêî ñòåïåíü ñíèæåíèÿ, íî è âåëè÷èíà îñòàòî÷íîé ïðîòåèíóðèè
    Exact
    [44]
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    .  ìåíåå ìàñøòàáíîì (n=332) èññëåäîâàíèè MARVAL (Microalbuminuria Reduction with Valsartan in patients with type 2 diabetes mellitus) ëå÷åíèå âàëñàðòàíîì (80 ìã/ñóò) â òå÷åíèå 24 íåä ñíèæàëî àëüáóìèíóðèþ íà 44% íåçàâèñèìî îò âåëè÷èíû ÀÄ è òîëüêî íà 8% – â ãðóïïå àìëîäèïèíà.

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Viberti G, Wheeldon NM. Microalbuminuria reduction with valsartan in patients with type 2 diabetes mellitus. A blood pressure–independent effect. Circulation 2002; 106: 672–678
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     ìåíåå ìàñøòàáíîì (n=332) èññëåäîâàíèè MARVAL (Microalbuminuria Reduction with Valsartan in patients with type 2 diabetes mellitus) ëå÷åíèå âàëñàðòàíîì (80 ìã/ñóò) â òå÷åíèå 24 íåä ñíèæàëî àëüáóìèíóðèþ íà 44% íåçàâèñèìî îò âåëè÷èíû ÀÄ è òîëüêî íà 8% – â ãðóïïå àìëîäèïèíà. Ñîîòâåòñòâåííî íîðìîàëüáóìèíóðèÿ áûëà äîñòèãíóòà ó 29,9 è 14,5% áîëüíûõ
    Exact
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    .  2 êðóïíåéøèõ èññëåäîâàíèÿõ LIFE (Losartan Intervention for Endpoint Reduction in Hypertension) è óïîìèíàâøåìñÿ RENAAL ïîëó÷åíû äîñòîâåðíûå äàííûå, ÷òî ñíèæåíèå àëüáóìèíóðèè íà ôîíå äëèòåëüíîãî àíòèãèïåðòåíçèâíîãî ëå÷åíèÿ àññîöèèðîâàíî ñ óìåíüøåíèåì ðèñêà ñåðäå÷íî-ñîñóäèñòîé ñìåðòíîñòè, èíôàðêòà è èíñóëüòà [46].

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Ibsen H, Olsen MH, Wachtell K et al. Reduction in Albuminuria Translates to Reduction in Cardiovascular Events in Hypertensive Patients. Hypertension 2005; 45: 198–202
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     2 êðóïíåéøèõ èññëåäîâàíèÿõ LIFE (Losartan Intervention for Endpoint Reduction in Hypertension) è óïîìèíàâøåìñÿ RENAAL ïîëó÷åíû äîñòîâåðíûå äàííûå, ÷òî ñíèæåíèå àëüáóìèíóðèè íà ôîíå äëèòåëüíîãî àíòèãèïåðòåíçèâíîãî ëå÷åíèÿ àññîöèèðîâàíî ñ óìåíüøåíèåì ðèñêà ñåðäå÷íî-ñîñóäèñòîé ñìåðòíîñòè, èíôàðêòà è èíñóëüòà
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    . Îäíèì èç âîçìîæíûõ ìåõàíèçìîâ êàðäèîïðîòåêòèâíîãî äåéñòâèÿ ëîçàðòàíà ÿâëÿåòñÿ åãî ñïîñîáíîñòü áîëåå ÷åì â 2 ðàçà ïî ñðàâíåíèþ ñ àòåíîëîëîì ñíèæàòü ñèñòîëè÷åñêîå è ïóëüñîâîå äàâëåíèå â àîðòå (ñîîòâåòñòâåííî íà 40 è 28 ìì ðò ñò.) çà ñ÷åò óìåíüøåíèÿ îòðàæåííîé îò ïåðèôåðèè ïóëüñîâîé âîëíû, õàðàêòåðèçóþùåé ðèãèäíîñòü (æåñòêîñòü) àðòåðèé [47].

47
Цветкова ОА, Мустафина МХ. Органопротективные возможности и безопасность блокаторов рецепторов ангиотензина II. РМЖ 2009; 17 (8): 600–606
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    Îäíèì èç âîçìîæíûõ ìåõàíèçìîâ êàðäèîïðîòåêòèâíîãî äåéñòâèÿ ëîçàðòàíà ÿâëÿåòñÿ åãî ñïîñîáíîñòü áîëåå ÷åì â 2 ðàçà ïî ñðàâíåíèþ ñ àòåíîëîëîì ñíèæàòü ñèñòîëè÷åñêîå è ïóëüñîâîå äàâëåíèå â àîðòå (ñîîòâåòñòâåííî íà 40 è 28 ìì ðò ñò.) çà ñ÷åò óìåíüøåíèÿ îòðàæåííîé îò ïåðèôåðèè ïóëüñîâîé âîëíû, õàðàêòåðèçóþùåé ðèãèäíîñòü (æåñòêîñòü) àðòåðèé
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    .  íåñêîëüêèõ íåäàâíî îïóáëèêîâàííûõ èññëåäîâàíèÿõ è ìåòà-àíàëèçàõ ïðîàíàëèçèðîâàíî âëèÿíèå áëîêàòîðîâ ÐÀÀÑ íà èñõîäû íåäèàáåòè÷åñêèõ íåôðîïàòèé. T. Jafar è ñîàâò. [48] ïîäûòîæèëè 11 èññëåäîâàíèé, â êîòîðûõ èçó÷àëîñü âëèÿíèå êîððåêöèè Àà ñ ïðèìåíåíèåì è áåç ïðèìåíåíèÿ ÈÀÏÔ ó 1860 áîëüíûõ ñ õðîíè÷åñêèìè çàáîëåâàíèÿìè ïî÷åê.

48
Jafar TH, Stark PC, Schmid CH et al. Progression of chronic kidney disease: the role of blood pressure control, proteinuria, and angiotensin–converting enzyme inhibition: a patient–level meta–analysis. Ann Intern Med 2003; 139: 244– 252
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    2 ðàçà ïî ñðàâíåíèþ ñ àòåíîëîëîì ñíèæàòü ñèñòîëè÷åñêîå è ïóëüñîâîå äàâëåíèå â àîðòå (ñîîòâåòñòâåííî íà 40 è 28 ìì ðò ñò.) çà ñ÷åò óìåíüøåíèÿ îòðàæåííîé îò ïåðèôåðèè ïóëüñîâîé âîëíû, õàðàêòåðèçóþùåé ðèãèäíîñòü (æåñòêîñòü) àðòåðèé [47].  íåñêîëüêèõ íåäàâíî îïóáëèêîâàííûõ èññëåäîâàíèÿõ è ìåòà-àíàëèçàõ ïðîàíàëèçèðîâàíî âëèÿíèå áëîêàòîðîâ ÐÀÀÑ íà èñõîäû íåäèàáåòè÷åñêèõ íåôðîïàòèé. T. Jafar è ñîàâò.
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    ïîäûòîæèëè 11 èññëåäîâàíèé, â êîòîðûõ èçó÷àëîñü âëèÿíèå êîððåêöèè Àà ñ ïðèìåíåíèåì è áåç ïðèìåíåíèÿ ÈÀÏÔ ó 1860 áîëüíûõ ñ õðîíè÷åñêèìè çàáîëåâàíèÿìè ïî÷åê. Ïåðèîä íàáëþäåíèÿ çà ïàöèåíòàìè ðàâíÿëñÿ â ñðåäíåì 2,2 ãîäà.

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    Áîëåå òîãî, íà ôîíå ëå÷åíèÿ ëèçèíîïðèëîì ÒÏÍ ó áîëüíûõ ÄÍ ðàçâèâàëàñü ÷àùå, ÷åì ïðè ïðèìåíåíèè õëîðòàëèäîíà (ó 25 èç 1563 ïðîòèâ 26 èç 2755), à ïî äàííûì S. Suissa è ñîàâò. [107], ó áîëüíûõ ÄÍ ñòàðøå 66 ëåò ïîñëå 3 ëåò ëå÷åíèÿ áëîêàòîðàìè ÐÀÀÑ ÷àñòîòà ÒÏÍ óâåëè÷èëàñü â 4,2 ðàçà. Ñîãëàñíî T. Jafar è ñîàâò.
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    è M. Kent è ñîàâò. [108], ñðåäè áîëüíûõ ñ íåäèàáåòè÷åñêîé íåôðîïàòèåé (n=1865) íå îòìå÷åíî ÈÀÏÔ-èíäóöèðîâàííîé íåôðîïðîòåêöèè ïðè ïðîòåèíóðèè <0,5 ã/ñóò. Ó 2954 áîëüíûõ ñ ñåðäå÷íî-ñîñóäèñòûìè çàáîëåâàíèÿìè èëè ÑÄ ëå÷åíèå òåëìèñàðòàíîì â äîçå 80 ìã/ñóò â òå÷åíèå 56 ìåñ çíà÷èìî íå âëèÿëî íà ïî÷å÷íûå èñõîäû ïî ñðàâíåíèþ ñ ïëàöåáî (n=2972) – óäâîåíèå êðåàòèíèíà ñûâîðîòêè (56 ïðîòèâ 36) èëè íåîáõîäèìî

49
Maschio G, Alberti D, Locatelli F et al. Angiotensin– converting enzyme inhibitors and kidney protection: the AIPRI trial. The ACE Inhibition in Progressive Renal Insufficiency (AIPRI) Study Group. J Cardiovasc Pharmacol 1999; 33 [Suppl 1]: S16–S20
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    Ïðîãðåññèðîâàíèå óñêîðÿëîñü ïðè ÑÀÄ < 110 ìì ðò ñò.  èññëåäîâàíèè AIPRI (The ACE Inhibition in Progressive Renal Insufficiency) ó 583 áîëüíûõ áåíàçåïðèë íà 50% ñíèæàë ÷àñòîòó óäâîåíèÿ êðåàòèíèíà ñûâîðîòêè è ðèñê ïåðåâîäà ïàöèåíòîâ íà äèàëèç
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    .  óïîìèíàâøåìñÿ èññëåäîâàíèè REIN çàìåäëåíèå ñíèæåíèÿ ÑÊÔ íà ôîíå êîíòðîëèðîâàíèÿ Àà îòìå÷åíî ó 166 áîëüíûõ ñ íåôðîòè÷åñêîé ïðîòåèíóðèåé. J. Casas è ñîàâò. [50] ïðîâåëè ìåòà-àíàëèç 127 èññëåäîâàíèé, âêëþ÷àâøèõ áîëüíûõ ñ äèàáåòè÷åñêîé è íåäèàáåòè÷åñêîé íåôðîïàòèÿìè.

50
Casas JP, Chua W, Loukogeorgakis S et al. Effect of inhibitors of the renin–angiotensin system and other antihypertensive drugs on renal outcomes: systematic review and meta–analysis. Lancet 2005; 366: 2026–2033
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     èññëåäîâàíèè AIPRI (The ACE Inhibition in Progressive Renal Insufficiency) ó 583 áîëüíûõ áåíàçåïðèë íà 50% ñíèæàë ÷àñòîòó óäâîåíèÿ êðåàòèíèíà ñûâîðîòêè è ðèñê ïåðåâîäà ïàöèåíòîâ íà äèàëèç [49].  óïîìèíàâøåìñÿ èññëåäîâàíèè REIN çàìåäëåíèå ñíèæåíèÿ ÑÊÔ íà ôîíå êîíòðîëèðîâàíèÿ Àà îòìå÷åíî ó 166 áîëüíûõ ñ íåôðîòè÷åñêîé ïðîòåèíóðèåé. J. Casas è ñîàâò.
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    ïðîâåëè ìåòà-àíàëèç 127 èññëåäîâàíèé, âêëþ÷àâøèõ áîëüíûõ ñ äèàáåòè÷åñêîé è íåäèàáåòè÷åñêîé íåôðîïàòèÿìè. ÈÀÏÔ è ÁÐÀ îêàçàëèñü íåñêîëüêî áîëåå ïîòåíòíûìè â ñíèæåíèè ðèñêà óäâîåíèÿ êðåàòèíèíà è äîñòèæåíèÿ òåðìèíàëüíîé óðåìèè, ÷åì äðóãèå àíòèãèïåðòåíçèâíûå ïðåïàðàòû, îäíàêî îíè îêàçûâàëè áîëåå âûðàæåííûé ãèïîòåíçèâíûé ýôôåêò, ÷åì, âåðîÿòíî, îáúÿñíÿåòñÿ ýòî ðàçëè÷èå.

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Hou FF, Zhang X, Zhang GH et al. Efficacy and safety of benazepril for advanced chronic renal insufficiency. N Engl J Med 2006; 354: 131–140
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    0 ìã/äë) ëå÷åíèå â òå÷åíèå 3,5 ëåò áåíàçåïðèëîì (20 ìã/ñóò) èëè ëîçàðòàíîì 100 ìã/ñóò ñíèæàëî ïî ñðàâíåíèþ ñ ïëàöåáî ðèñê óäâîåíèÿ êðåàòèíèíà ñûâîðîòêè íà 51% è íà 53% – ðèñê ðàçâèòèÿ òåðìèíàëüíîé óðåìèè. Ó áîëüíûõ ÑÄ áëîêàòîðû ÐÀÀÑ íå âûçûâàëè äîïîëíèòåëüíûå íåôðîïðîòåêòèâíûå ýôôåêòû, êðîìå îáóñëîâëåííûõ êîíòðîëåì ÀÃ. Íåôðîïðîòåêòèâíûå ýôôåêòû ÈÀÏÔ è ÁÐÀ óñèëèâàëèñü ïðè èõ ñîâìåñòíîì ïðèìåíåíèè
    Exact
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    . Ñî÷åòàííàÿ áëîêàäà ÐÀÀÑ Ïî äàííûì F. Catapano è ñîàâò. [52], ïðîàíàëèçèðîâàâøèõ 13 ðàíäîìèçèðîâàííûõ êîíòðîëèðóåìûõ èññëåäîâàíèé (ÐÊÈ) ñ îõâàòîì 425 áîëüíûõ ïåðâè÷íûì ãëîìåðóëîíåôðèòîì, óñòàíîâëåíî, ÷òî ñíèæåíèå ïðîòåèíóðèè áûëî íàèáîëåå çíà÷èòåëüíûì íà ôîíå êîìáèíèðîâàííîé òåðàïèè (ÊÎÒ) ÈÀÏÔ è ÁÐÀ ïî ñðàâíåíèþ ñ ìîíîòåðàïèåé òîëüêî ÈÀÏÔ.

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Catapano F, Chiodini P, Nicola LD et al. Antiproteinuric response to dual blockade of the renin–angiotensin system in primary glomerulonephritis: meta–analysis and metaregression. Am J Kidney Dis 2008; 52: 475–485
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    Ó áîëüíûõ ÑÄ áëîêàòîðû ÐÀÀÑ íå âûçûâàëè äîïîëíèòåëüíûå íåôðîïðîòåêòèâíûå ýôôåêòû, êðîìå îáóñëîâëåííûõ êîíòðîëåì ÀÃ. Íåôðîïðîòåêòèâíûå ýôôåêòû ÈÀÏÔ è ÁÐÀ óñèëèâàëèñü ïðè èõ ñîâìåñòíîì ïðèìåíåíèè [51]. Ñî÷åòàííàÿ áëîêàäà ÐÀÀÑ Ïî äàííûì F. Catapano è ñîàâò.
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    , ïðîàíàëèçèðîâàâøèõ 13 ðàíäîìèçèðîâàííûõ êîíòðîëèðóåìûõ èññëåäîâàíèé (ÐÊÈ) ñ îõâàòîì 425 áîëüíûõ ïåðâè÷íûì ãëîìåðóëîíåôðèòîì, óñòàíîâëåíî, ÷òî ñíèæåíèå ïðîòåèíóðèè áûëî íàèáîëåå çíà÷èòåëüíûì íà ôîíå êîìáèíèðîâàííîé òåðàïèè (ÊÎÒ) ÈÀÏÔ è ÁÐÀ ïî ñðàâíåíèþ ñ ìîíîòåðàïèåé òîëüêî ÈÀÏÔ.

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Jennings DL, Kalus JS, Coleman CI et al. Combination therapy with an ACE inhibitor and an angiotensin receptor blocker for diabetic nephropathy: a meta–analysis. Diabet Med 2007; 24: 486–493
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    Catapano è ñîàâò. [52], ïðîàíàëèçèðîâàâøèõ 13 ðàíäîìèçèðîâàííûõ êîíòðîëèðóåìûõ èññëåäîâàíèé (ÐÊÈ) ñ îõâàòîì 425 áîëüíûõ ïåðâè÷íûì ãëîìåðóëîíåôðèòîì, óñòàíîâëåíî, ÷òî ñíèæåíèå ïðîòåèíóðèè áûëî íàèáîëåå çíà÷èòåëüíûì íà ôîíå êîìáèíèðîâàííîé òåðàïèè (ÊÎÒ) ÈÀÏÔ è ÁÐÀ ïî ñðàâíåíèþ ñ ìîíîòåðàïèåé òîëüêî ÈÀÏÔ. ÈÀÏÔ â íåáîëüøèõ äîçàõ â ìåíüøåé ñòåïåíè ñíèæàëè ïðîòåèíóðèþ, ÷åì ÊÎÒ
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    , îäíàêî ïðè íàçíà÷åíèè èíãèáèòîðîâ â ìàêñèìàëüíûõ äîçàõ ýòî ðàçëè÷èå íèâåëèðîâàëîñü [54]. R. Kunz è ñîàâò. [55] ïðîâåëè ìåòà-àíàëèç 49 ÐÊÈ, ïîñâÿùåííûõ ïðèìåíåíèþ áëîêàòîðîâ ÐÀÀÑ ó áîëüíûõ ñ íåôðîïàòèÿìè, è óñòàíîâèëè, ÷òî íà ôîíå ñî÷åòàííîãî ëå÷åíèÿ ÈÀÏÔ è ÁÐÀ ïðîòåèíóðèÿ áûëà íà 25% íèæå, ÷åì ïðè òåðàïèè ÁÐÀ è íà 22% – ïðè èñïîëüçîâàíèè ÈÀÏÔ.

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Bakris GL, Ruilope L, Locatelli F et al. Treatment of microalbuminuria in hypertensive subjects with elevated cardiovascular risk: results of the IMPROVE trial. Kidney Int 2007; 72: 879–885
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    êîíòðîëèðóåìûõ èññëåäîâàíèé (ÐÊÈ) ñ îõâàòîì 425 áîëüíûõ ïåðâè÷íûì ãëîìåðóëîíåôðèòîì, óñòàíîâëåíî, ÷òî ñíèæåíèå ïðîòåèíóðèè áûëî íàèáîëåå çíà÷èòåëüíûì íà ôîíå êîìáèíèðîâàííîé òåðàïèè (ÊÎÒ) ÈÀÏÔ è ÁÐÀ ïî ñðàâíåíèþ ñ ìîíîòåðàïèåé òîëüêî ÈÀÏÔ. ÈÀÏÔ â íåáîëüøèõ äîçàõ â ìåíüøåé ñòåïåíè ñíèæàëè ïðîòåèíóðèþ, ÷åì ÊÎÒ [53], îäíàêî ïðè íàçíà÷åíèè èíãèáèòîðîâ â ìàêñèìàëüíûõ äîçàõ ýòî ðàçëè÷èå íèâåëèðîâàëîñü
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    . R. Kunz è ñîàâò. [55] ïðîâåëè ìåòà-àíàëèç 49 ÐÊÈ, ïîñâÿùåííûõ ïðèìåíåíèþ áëîêàòîðîâ ÐÀÀÑ ó áîëüíûõ ñ íåôðîïàòèÿìè, è óñòàíîâèëè, ÷òî íà ôîíå ñî÷åòàííîãî ëå÷åíèÿ ÈÀÏÔ è ÁÐÀ ïðîòåèíóðèÿ áûëà íà 25% íèæå, ÷åì ïðè òåðàïèè ÁÐÀ è íà 22% – ïðè èñïîëüçîâàíèè ÈÀÏÔ.

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Kunz R, Friedrich C, Wolbers M, Mann JF. Meta–analysis: effect of monotherapy and combination therapy with inhibitors of the renin–angiotensin system on proteinuria in renal disease. Ann Intern Med 2008; 148: 30–48
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    (ÐÊÈ) ñ îõâàòîì 425 áîëüíûõ ïåðâè÷íûì ãëîìåðóëîíåôðèòîì, óñòàíîâëåíî, ÷òî ñíèæåíèå ïðîòåèíóðèè áûëî íàèáîëåå çíà÷èòåëüíûì íà ôîíå êîìáèíèðîâàííîé òåðàïèè (ÊÎÒ) ÈÀÏÔ è ÁÐÀ ïî ñðàâíåíèþ ñ ìîíîòåðàïèåé òîëüêî ÈÀÏÔ. ÈÀÏÔ â íåáîëüøèõ äîçàõ â ìåíüøåé ñòåïåíè ñíèæàëè ïðîòåèíóðèþ, ÷åì ÊÎÒ [53], îäíàêî ïðè íàçíà÷åíèè èíãèáèòîðîâ â ìàêñèìàëüíûõ äîçàõ ýòî ðàçëè÷èå íèâåëèðîâàëîñü [54]. R. Kunz è ñîàâò.
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    ïðîâåëè ìåòà-àíàëèç 49 ÐÊÈ, ïîñâÿùåííûõ ïðèìåíåíèþ áëîêàòîðîâ ÐÀÀÑ ó áîëüíûõ ñ íåôðîïàòèÿìè, è óñòàíîâèëè, ÷òî íà ôîíå ñî÷åòàííîãî ëå÷åíèÿ ÈÀÏÔ è ÁÐÀ ïðîòåèíóðèÿ áûëà íà 25% íèæå, ÷åì ïðè òåðàïèè ÁÐÀ è íà 22% – ïðè èñïîëüçîâàíèè ÈÀÏÔ.

56
Agodoa LY, Appel L., Bakris GL et al. Effect of ramipril vs amlodipine on renal outcomes in hypertensive nephrosclerosis: a randomized controlled trial. JAMA 2001; 285: 2719–2728
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    Ïîñëåäíèå çàìåäëÿëè ñíèæåíèå CÊÔ è ó áîëüíûõ ñ íåâûñîêîé ïðîòåèíóðèåé. Ïðè ãèïåðòåíçèâíîì íåôðîñêëåðîçå, ïðîòåêàþùåì ñî ñëåäîâûì êîëè÷åñòâîì áåëêà â ìî÷å, ÈÀÏÔ çíà÷èòåëüíåå ïðåäóïðåæäàëè ïðîãðåññèðîâàíèå íåôðîïàòèè, ÷åì àìëîäèïèí
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    . Î ïðåèìóùåñòâàõ ÊÎÒ â ïëàíå ñíèæåíèÿ ÀÄ, êîíöåíòðàöèè àëüäîñòåðîíà â ñûâîðîòêå, ïðîòåèíóðèè ñ óìåíüøåíèåì ýêñêðåöèè ÒÔÐ-β1 è, â êîíå÷íîì èòîãå, çàìåäëåíèÿ ïðîãðåññèðîâàíèÿ ÄÍ ñâèäåòåëüñòâóþò äàííûå J.

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Matos J, de Lourdes Rodriguez M, Ismerim V et al. Effects of dual blockade of the renin angiotensin system inhypertensive type 2 diabetic patients with nephropathy. Clin Nephrol 2005; 64: 180–189
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    Î ïðåèìóùåñòâàõ ÊÎÒ â ïëàíå ñíèæåíèÿ ÀÄ, êîíöåíòðàöèè àëüäîñòåðîíà â ñûâîðîòêå, ïðîòåèíóðèè ñ óìåíüøåíèåì ýêñêðåöèè ÒÔÐ-β1 è, â êîíå÷íîì èòîãå, çàìåäëåíèÿ ïðîãðåññèðîâàíèÿ ÄÍ ñâèäåòåëüñòâóþò äàííûå J. Matos è ñîàâò.
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    è K. Rossing è ñîàâò. [58], îäíàêî íå âûÿâëåíî ðàçëè÷èé â àíòèãèïåðòåíçèâíîì ýôôåêòå êàíäåñàðòàíà â äîçå 10 ìã/ñóò è ëèçèíîïðèëà (20 ìã/ñóò) èëè òîëüêî ëèçèíîïðèëà â äîçå 40 ìã/ñóò [59].  íåäàâíî çàâåðøèâøåìñÿ èññëåäîâàíèè ADVANCE (Action in Diabetes and Vascular Disease – Preferax and Diamicron MR Controlled Evaluation) ñî÷åòàííîå ïðèìåíåíèå ó áîëüíûõ äèàáåòîì òèïà 2 (n=11 140) äèàáåòîíà Ì è í

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Rossing K, Christensen PK, Jensen BR, Parving HH. Dual blockade of the renin–angiotensin system in diabetic nephropathy: a randomized double–blind crossover study. Diabetes Care 2002; 25: 95–100
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    Î ïðåèìóùåñòâàõ ÊÎÒ â ïëàíå ñíèæåíèÿ ÀÄ, êîíöåíòðàöèè àëüäîñòåðîíà â ñûâîðîòêå, ïðîòåèíóðèè ñ óìåíüøåíèåì ýêñêðåöèè ÒÔÐ-β1 è, â êîíå÷íîì èòîãå, çàìåäëåíèÿ ïðîãðåññèðîâàíèÿ ÄÍ ñâèäåòåëüñòâóþò äàííûå J. Matos è ñîàâò. [57] è K. Rossing è ñîàâò.
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    , îäíàêî íå âûÿâëåíî ðàçëè÷èé â àíòèãèïåðòåíçèâíîì ýôôåêòå êàíäåñàðòàíà â äîçå 10 ìã/ñóò è ëèçèíîïðèëà (20 ìã/ñóò) èëè òîëüêî ëèçèíîïðèëà â äîçå 40 ìã/ñóò [59].  íåäàâíî çàâåðøèâøåìñÿ èññëåäîâàíèè ADVANCE (Action in Diabetes and Vascular Disease – Preferax and Diamicron MR Controlled Evaluation) ñî÷åòàííîå ïðèìåíåíèå ó áîëüíûõ äèàáåòîì òèïà 2 (n=11 140) äèàáåòîíà Ì è íîëèïðåëà ôîðòå (ïåðèíäîïðèë

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Andersen NH, Poulsen PL, Knudsen ST et al. Long– term dual blockade with candesartan and lisinopril in hypertensive patients with diabetes. The CALM II study. Diabetes Care 2005; 28: 273–277
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  1. In-text reference with the coordinate start=17304
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    Matos è ñîàâò. [57] è K. Rossing è ñîàâò. [58], îäíàêî íå âûÿâëåíî ðàçëè÷èé â àíòèãèïåðòåíçèâíîì ýôôåêòå êàíäåñàðòàíà â äîçå 10 ìã/ñóò è ëèçèíîïðèëà (20 ìã/ñóò) èëè òîëüêî ëèçèíîïðèëà â äîçå 40 ìã/ñóò
    Exact
    [59]
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    .  íåäàâíî çàâåðøèâøåìñÿ èññëåäîâàíèè ADVANCE (Action in Diabetes and Vascular Disease – Preferax and Diamicron MR Controlled Evaluation) ñî÷åòàííîå ïðèìåíåíèå ó áîëüíûõ äèàáåòîì òèïà 2 (n=11 140) äèàáåòîíà Ì è íîëèïðåëà ôîðòå (ïåðèíäîïðèë 2 ìã + èíäàïàìèä 0,6–1,2 ìã/ñóò), îáåñïå÷èâøèõ ñòðîãèé êîíòðîëü ãëèêåìèè è ÀÄ, ðàçâèòèå è ïðîãðåññèðîâàíèå ÄÍ çàìåäëèëèñü íà 33%, ðèñê îáùåé è ñåðäå÷íî-ñîñóäè

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The ADVANCE Collaborative Group. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 2008; 358: 2560–2572
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    (Action in Diabetes and Vascular Disease – Preferax and Diamicron MR Controlled Evaluation) ñî÷åòàííîå ïðèìåíåíèå ó áîëüíûõ äèàáåòîì òèïà 2 (n=11 140) äèàáåòîíà Ì è íîëèïðåëà ôîðòå (ïåðèíäîïðèë 2 ìã + èíäàïàìèä 0,6–1,2 ìã/ñóò), îáåñïå÷èâøèõ ñòðîãèé êîíòðîëü ãëèêåìèè è ÀÄ, ðàçâèòèå è ïðîãðåññèðîâàíèå ÄÍ çàìåäëèëèñü íà 33%, ðèñê îáùåé è ñåðäå÷íî-ñîñóäèñòîé ñìåðòíîñòè óìåíüøèëñÿ íà 18% è 24%
    Exact
    [60]
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    .  èññëåäîâàíèè COOPERATE (Combination treatment of angiotensin-II receptor blocker and angiotensin-converting-enzyme inhibitor in non-diabetic renal disease) N. Nakao è ñîàâò. [61] 263 áîëüíûì ñ íåäèàáåòè÷åñêîé íåôðîïàòèåé íàçíà÷àëè èëè ëîçàðòàí (100 ìã/ñóò), èëè òðàíäîëàïðèë (3 ìã/ñóò), èëè îäíîâðåìåííî îáà ïðåïàðàòà.

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Nakao M, Yoshimura A, Morita M et al. Combination treatment of angiotensin–II receptor blocker and angiotensin– converting–enzyme inhibitor in non–diabetic renal disease (COOPERATE): A randomised controlled trial. Lancet 2003; 361: 117–124
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    ôîðòå (ïåðèíäîïðèë 2 ìã + èíäàïàìèä 0,6–1,2 ìã/ñóò), îáåñïå÷èâøèõ ñòðîãèé êîíòðîëü ãëèêåìèè è ÀÄ, ðàçâèòèå è ïðîãðåññèðîâàíèå ÄÍ çàìåäëèëèñü íà 33%, ðèñê îáùåé è ñåðäå÷íî-ñîñóäèñòîé ñìåðòíîñòè óìåíüøèëñÿ íà 18% è 24% [60].  èññëåäîâàíèè COOPERATE (Combination treatment of angiotensin-II receptor blocker and angiotensin-converting-enzyme inhibitor in non-diabetic renal disease) N. Nakao è ñîàâò.
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    263 áîëüíûì ñ íåäèàáåòè÷åñêîé íåôðîïàòèåé íàçíà÷àëè èëè ëîçàðòàí (100 ìã/ñóò), èëè òðàíäîëàïðèë (3 ìã/ñóò), èëè îäíîâðåìåííî îáà ïðåïàðàòà. ÊÎÒ â ñðàâíåíèè ñ ìîíîòåðàïèåé áëîêàòîðàìè ÐÀÀÑ â áîëüøåé ñòåïåíè çàìåäëÿëà ïðîãðåññèðîâàíèå, íå âûçûâàÿ ñåðüåçíûõ ïîáî÷íûõ ðåàêöèé.

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Fox KM. European trial on reduction of cardiac events with perindopril in stable coronary Artery disease Investigators. Lancet 2003; 362: 782–788
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    Íà ôîíå äëèòåëüíîãî (4,2 ãîäà) ëå÷åíèÿ ïåðèíäîïðèëîì (8 ìã/ñóò) ðèñê äîñòèæåíèÿ êîíå÷íîé òî÷êè ñíèçèëñÿ íà 20% ïî ñðàâíåíèþ ñ ïëàöåáî, â êðîâè óìåíüøèëñÿ óðîâåíü ôàêòîðà Âèëëåáðàíäà, ñâèäåòåëüñòâóÿ îá óëó÷øåíèè ýíäîòåëèàëüíîé ôóíêöèè, ïîâûñèëàñü ýêñïðåññèÿ ýíäîòåëèàëüíîé NOñèíòàçû è îòìå÷àëîñü ïîäàâëåíèå àïîïòîçà
    Exact
    [62, 63]
    Suffix
    .  èññëåäîâàíèè MICRO-HOPE èçó÷àëè âëèÿíèå ðàìèïðèëà (n=1808) íà ïåðâè÷íûå (èíôàðêò ìèîêàðäà, èíñóëüò, ñìåðòü) è âòîðè÷íûå (ãîñïèòàëèçàöèÿ â ñâÿçè ñ íåñòàáèëüíîé ñòåíîêàðäèåé, ñåðäå÷íîé íåäîñòàòî÷íîñòüþ, êîðîíàðíîé ðåâàñêóëÿðèçàöèåé è ðàçâèòèåì ÄÍ) èñõîäû â ñðàâíåíèè ñ ïëàöåáî (n=1756).

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    Íà ôîíå ïðèåìà ðàìèïðèëà ðèñê ñìåðòåëüíûõ èñõîäîâ ñíèçèëñÿ íà 24%, ðåâàñêóëÿðèçàöèè – íà 17% è ÄÍ – íà 24%. Ýôôåêòû ðàìèïðèëà áûëè îò÷åòëèâåå ó ïàöèåíòîâ ñ èñõîäíîé áîëåå âûðàæåííîé ñåðäå÷íî-ñîñóäèñòîé ïàòîëîãèåé [64]. Íàðÿäó ñ çàìåäëåíèåì àòåðîñêëåðîòè÷åñêîãî ïîðàæåíèÿ îðãàíîâ
    Exact
    [62]
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    , ÈÀÏÔ òîðìîçÿò è àòåðîñêëåðîç ñîííûõ è ìîçãîâûõ àðòåðèé [65], õîòÿ â òàêîé æå ñòåïåíè ïðåäóïðåæäàòü óòîëùåíèå èíòèìû–ìåäèà ñîííûõ àðòåðèé ñïîñîáíû è áëîêàòîðû êàëüöèåâûõ êàíàëîâ (èññëåäîâàíèÿ MIDAS, VHAS, ELSA) [66–68].

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Ceconi С, Fох КM, Remme WJ et al. ACE inhibition with perindopril and endothelial function. Results of a substudy of the EUROPA study: PERTINEN. Cardiovasc Res 2007; 73 (1): 237–246
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    Íà ôîíå äëèòåëüíîãî (4,2 ãîäà) ëå÷åíèÿ ïåðèíäîïðèëîì (8 ìã/ñóò) ðèñê äîñòèæåíèÿ êîíå÷íîé òî÷êè ñíèçèëñÿ íà 20% ïî ñðàâíåíèþ ñ ïëàöåáî, â êðîâè óìåíüøèëñÿ óðîâåíü ôàêòîðà Âèëëåáðàíäà, ñâèäåòåëüñòâóÿ îá óëó÷øåíèè ýíäîòåëèàëüíîé ôóíêöèè, ïîâûñèëàñü ýêñïðåññèÿ ýíäîòåëèàëüíîé NOñèíòàçû è îòìå÷àëîñü ïîäàâëåíèå àïîïòîçà
    Exact
    [62, 63]
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    .  èññëåäîâàíèè MICRO-HOPE èçó÷àëè âëèÿíèå ðàìèïðèëà (n=1808) íà ïåðâè÷íûå (èíôàðêò ìèîêàðäà, èíñóëüò, ñìåðòü) è âòîðè÷íûå (ãîñïèòàëèçàöèÿ â ñâÿçè ñ íåñòàáèëüíîé ñòåíîêàðäèåé, ñåðäå÷íîé íåäîñòàòî÷íîñòüþ, êîðîíàðíîé ðåâàñêóëÿðèçàöèåé è ðàçâèòèåì ÄÍ) èñõîäû â ñðàâíåíèè ñ ïëàöåáî (n=1756).

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Heart Outcome Prevention Evaluation (HOPE) Study Investigators. Effect of ramipril on cardiovascular and microvascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Lancet 2000; 355: 253–259
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    Íà ôîíå ïðèåìà ðàìèïðèëà ðèñê ñìåðòåëüíûõ èñõîäîâ ñíèçèëñÿ íà 24%, ðåâàñêóëÿðèçàöèè – íà 17% è ÄÍ – íà 24%. Ýôôåêòû ðàìèïðèëà áûëè îò÷åòëèâåå ó ïàöèåíòîâ ñ èñõîäíîé áîëåå âûðàæåííîé ñåðäå÷íî-ñîñóäèñòîé ïàòîëîãèåé
    Exact
    [64]
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    . Íàðÿäó ñ çàìåäëåíèåì àòåðîñêëåðîòè÷åñêîãî ïîðàæåíèÿ îðãàíîâ [62], ÈÀÏÔ òîðìîçÿò è àòåðîñêëåðîç ñîííûõ è ìîçãîâûõ àðòåðèé [65], õîòÿ â òàêîé æå ñòåïåíè ïðåäóïðåæäàòü óòîëùåíèå èíòèìû–ìåäèà ñîííûõ àðòåðèé ñïîñîáíû è áëîêàòîðû êàëüöèåâûõ êàíàëîâ (èññëåäîâàíèÿ MIDAS, VHAS, ELSA) [66–68].

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Zanchetti A, Crepaldi G, Bond MG et al. Different effects of antihypertensive regimens based on fosinopril or hydrochlorothiazide with or without lipid lowering by pravastatin on progression of asymptomatic carotid atheroscle-rosis: principal results of PHYLLIS – a randomized double–blind trial. Stroke 2004; 35: 2807–2812
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    Ýôôåêòû ðàìèïðèëà áûëè îò÷åòëèâåå ó ïàöèåíòîâ ñ èñõîäíîé áîëåå âûðàæåííîé ñåðäå÷íî-ñîñóäèñòîé ïàòîëîãèåé [64]. Íàðÿäó ñ çàìåäëåíèåì àòåðîñêëåðîòè÷åñêîãî ïîðàæåíèÿ îðãàíîâ [62], ÈÀÏÔ òîðìîçÿò è àòåðîñêëåðîç ñîííûõ è ìîçãîâûõ àðòåðèé
    Exact
    [65]
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    , õîòÿ â òàêîé æå ñòåïåíè ïðåäóïðåæäàòü óòîëùåíèå èíòèìû–ìåäèà ñîííûõ àðòåðèé ñïîñîáíû è áëîêàòîðû êàëüöèåâûõ êàíàëîâ (èññëåäîâàíèÿ MIDAS, VHAS, ELSA) [66–68]. ÕÑÍ âñòðå÷àåòñÿ â 5% â îáùåé ïîïóëÿöèè è ó 37% áîëüíûõ, ïîñòóïàþùèõ íà ëå÷åíèå ãåìîäèàëèçîì [69].

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    Íàðÿäó ñ çàìåäëåíèåì àòåðîñêëåðîòè÷åñêîãî ïîðàæåíèÿ îðãàíîâ [62], ÈÀÏÔ òîðìîçÿò è àòåðîñêëåðîç ñîííûõ è ìîçãîâûõ àðòåðèé [65], õîòÿ â òàêîé æå ñòåïåíè ïðåäóïðåæäàòü óòîëùåíèå èíòèìû–ìåäèà ñîííûõ àðòåðèé ñïîñîáíû è áëîêàòîðû êàëüöèåâûõ êàíàëîâ (èññëåäîâàíèÿ MIDAS, VHAS, ELSA)
    Exact
    [66–68]
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    . ÕÑÍ âñòðå÷àåòñÿ â 5% â îáùåé ïîïóëÿöèè è ó 37% áîëüíûõ, ïîñòóïàþùèõ íà ëå÷åíèå ãåìîäèàëèçîì [69]. Ëå÷åíèå ÈÀÏÔ è ÁÐÀ ñíèæàåò ëåòàëüíîñòü áîëüíûõ ñ ÕÑÍ [70], ÷òî â îòíîøåíèè ÈÀÏÔ çàêðåïëåíî â èíîñòðàííûõ è îòå÷åñòâåííûõ ðåêîìåíäàöèÿõ [71, 72], îäíàêî ìíåíèå îá ýôôåêòèâíîñòè ÁÐÀ è ÊÎÒ íå ñòîëü åäèíîäóøíî.

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    Íàðÿäó ñ çàìåäëåíèåì àòåðîñêëåðîòè÷åñêîãî ïîðàæåíèÿ îðãàíîâ [62], ÈÀÏÔ òîðìîçÿò è àòåðîñêëåðîç ñîííûõ è ìîçãîâûõ àðòåðèé [65], õîòÿ â òàêîé æå ñòåïåíè ïðåäóïðåæäàòü óòîëùåíèå èíòèìû–ìåäèà ñîííûõ àðòåðèé ñïîñîáíû è áëîêàòîðû êàëüöèåâûõ êàíàëîâ (èññëåäîâàíèÿ MIDAS, VHAS, ELSA)
    Exact
    [66–68]
    Suffix
    . ÕÑÍ âñòðå÷àåòñÿ â 5% â îáùåé ïîïóëÿöèè è ó 37% áîëüíûõ, ïîñòóïàþùèõ íà ëå÷åíèå ãåìîäèàëèçîì [69]. Ëå÷åíèå ÈÀÏÔ è ÁÐÀ ñíèæàåò ëåòàëüíîñòü áîëüíûõ ñ ÕÑÍ [70], ÷òî â îòíîøåíèè ÈÀÏÔ çàêðåïëåíî â èíîñòðàííûõ è îòå÷åñòâåííûõ ðåêîìåíäàöèÿõ [71, 72], îäíàêî ìíåíèå îá ýôôåêòèâíîñòè ÁÐÀ è ÊÎÒ íå ñòîëü åäèíîäóøíî.

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Zanchetti A, Bond MG, Hennig M et al. Calcium antagonist lacidipine slows down progression of asymptomatic carotid atherosclerosis. Principal Results of the European Lacidipine Study on Atherosclerosis (ELSA), a randomized, double–blind, long–term trial. Circulation 2002; 106: 2422–2427
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    Íàðÿäó ñ çàìåäëåíèåì àòåðîñêëåðîòè÷åñêîãî ïîðàæåíèÿ îðãàíîâ [62], ÈÀÏÔ òîðìîçÿò è àòåðîñêëåðîç ñîííûõ è ìîçãîâûõ àðòåðèé [65], õîòÿ â òàêîé æå ñòåïåíè ïðåäóïðåæäàòü óòîëùåíèå èíòèìû–ìåäèà ñîííûõ àðòåðèé ñïîñîáíû è áëîêàòîðû êàëüöèåâûõ êàíàëîâ (èññëåäîâàíèÿ MIDAS, VHAS, ELSA)
    Exact
    [66–68]
    Suffix
    . ÕÑÍ âñòðå÷àåòñÿ â 5% â îáùåé ïîïóëÿöèè è ó 37% áîëüíûõ, ïîñòóïàþùèõ íà ëå÷åíèå ãåìîäèàëèçîì [69]. Ëå÷åíèå ÈÀÏÔ è ÁÐÀ ñíèæàåò ëåòàëüíîñòü áîëüíûõ ñ ÕÑÍ [70], ÷òî â îòíîøåíèè ÈÀÏÔ çàêðåïëåíî â èíîñòðàííûõ è îòå÷åñòâåííûõ ðåêîìåíäàöèÿõ [71, 72], îäíàêî ìíåíèå îá ýôôåêòèâíîñòè ÁÐÀ è ÊÎÒ íå ñòîëü åäèíîäóøíî.

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    Íàðÿäó ñ çàìåäëåíèåì àòåðîñêëåðîòè÷åñêîãî ïîðàæåíèÿ îðãàíîâ [62], ÈÀÏÔ òîðìîçÿò è àòåðîñêëåðîç ñîííûõ è ìîçãîâûõ àðòåðèé [65], õîòÿ â òàêîé æå ñòåïåíè ïðåäóïðåæäàòü óòîëùåíèå èíòèìû–ìåäèà ñîííûõ àðòåðèé ñïîñîáíû è áëîêàòîðû êàëüöèåâûõ êàíàëîâ (èññëåäîâàíèÿ MIDAS, VHAS, ELSA) [66–68]. ÕÑÍ âñòðå÷àåòñÿ â 5% â îáùåé ïîïóëÿöèè è ó 37% áîëüíûõ, ïîñòóïàþùèõ íà ëå÷åíèå ãåìîäèàëèçîì
    Exact
    [69]
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    . Ëå÷åíèå ÈÀÏÔ è ÁÐÀ ñíèæàåò ëåòàëüíîñòü áîëüíûõ ñ ÕÑÍ [70], ÷òî â îòíîøåíèè ÈÀÏÔ çàêðåïëåíî â èíîñòðàííûõ è îòå÷åñòâåííûõ ðåêîìåíäàöèÿõ [71, 72], îäíàêî ìíåíèå îá ýôôåêòèâíîñòè ÁÐÀ è ÊÎÒ íå ñòîëü åäèíîäóøíî.

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Berger AK, Duval S, Manske C et al. Angiotensin– converting enzyme inhibitors and angiotensin receptor blockers in patients with congestive heart failure and chronic kidney disease. Am Heart J 2007; 153: 1064–1073
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    ïîðàæåíèÿ îðãàíîâ [62], ÈÀÏÔ òîðìîçÿò è àòåðîñêëåðîç ñîííûõ è ìîçãîâûõ àðòåðèé [65], õîòÿ â òàêîé æå ñòåïåíè ïðåäóïðåæäàòü óòîëùåíèå èíòèìû–ìåäèà ñîííûõ àðòåðèé ñïîñîáíû è áëîêàòîðû êàëüöèåâûõ êàíàëîâ (èññëåäîâàíèÿ MIDAS, VHAS, ELSA) [66–68]. ÕÑÍ âñòðå÷àåòñÿ â 5% â îáùåé ïîïóëÿöèè è ó 37% áîëüíûõ, ïîñòóïàþùèõ íà ëå÷åíèå ãåìîäèàëèçîì [69]. Ëå÷åíèå ÈÀÏÔ è ÁÐÀ ñíèæàåò ëåòàëüíîñòü áîëüíûõ ñ ÕÑÍ
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    [70]
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    , ÷òî â îòíîøåíèè ÈÀÏÔ çàêðåïëåíî â èíîñòðàííûõ è îòå÷åñòâåííûõ ðåêîìåíäàöèÿõ [71, 72], îäíàêî ìíåíèå îá ýôôåêòèâíîñòè ÁÐÀ è ÊÎÒ íå ñòîëü åäèíîäóøíî. Ïî äàííûì V. Lee è ñîàâò. [73], îáðàáîòàâøèõ ðåçóëüòàòû 7 ÐÊÈ, ó áîëüíûõ ñ ÕÑÍ ÊÎÒ íà 23% óìåíüøàëà ÷àñòîòó ãîñïèòàëèçàöèé, íî íå âëèÿëà íà ëåòàëüíîñòü.

71
Диагностика и лечение артериальной гипертензии. Рекомендации Российского медицинского общества по артериальной гипертонии и Всероссийского научного общества кардиологов (третий пересмотр). Кардиоваскулярная терапия и профилактика 2008; 7 (6) (приложение 2): 1–30
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    ÕÑÍ âñòðå÷àåòñÿ â 5% â îáùåé ïîïóëÿöèè è ó 37% áîëüíûõ, ïîñòóïàþùèõ íà ëå÷åíèå ãåìîäèàëèçîì [69]. Ëå÷åíèå ÈÀÏÔ è ÁÐÀ ñíèæàåò ëåòàëüíîñòü áîëüíûõ ñ ÕÑÍ [70], ÷òî â îòíîøåíèè ÈÀÏÔ çàêðåïëåíî â èíîñòðàííûõ è îòå÷åñòâåííûõ ðåêîìåíäàöèÿõ
    Exact
    [71, 72]
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    , îäíàêî ìíåíèå îá ýôôåêòèâíîñòè ÁÐÀ è ÊÎÒ íå ñòîëü åäèíîäóøíî. Ïî äàííûì V. Lee è ñîàâò. [73], îáðàáîòàâøèõ ðåçóëüòàòû 7 ÐÊÈ, ó áîëüíûõ ñ ÕÑÍ ÊÎÒ íà 23% óìåíüøàëà ÷àñòîòó ãîñïèòàëèçàöèé, íî íå âëèÿëà íà ëåòàëüíîñòü.

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K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kidney Dis 2004; 43 [Suppl 1]: S1–S290
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    ÕÑÍ âñòðå÷àåòñÿ â 5% â îáùåé ïîïóëÿöèè è ó 37% áîëüíûõ, ïîñòóïàþùèõ íà ëå÷åíèå ãåìîäèàëèçîì [69]. Ëå÷åíèå ÈÀÏÔ è ÁÐÀ ñíèæàåò ëåòàëüíîñòü áîëüíûõ ñ ÕÑÍ [70], ÷òî â îòíîøåíèè ÈÀÏÔ çàêðåïëåíî â èíîñòðàííûõ è îòå÷åñòâåííûõ ðåêîìåíäàöèÿõ
    Exact
    [71, 72]
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    , îäíàêî ìíåíèå îá ýôôåêòèâíîñòè ÁÐÀ è ÊÎÒ íå ñòîëü åäèíîäóøíî. Ïî äàííûì V. Lee è ñîàâò. [73], îáðàáîòàâøèõ ðåçóëüòàòû 7 ÐÊÈ, ó áîëüíûõ ñ ÕÑÍ ÊÎÒ íà 23% óìåíüøàëà ÷àñòîòó ãîñïèòàëèçàöèé, íî íå âëèÿëà íà ëåòàëüíîñòü.

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Lee VC, Rhew DC, Dylan M et al. Meta–analysis: angiotensin–receptor blockers in chronic heart failure and high–risk acute myocardial infarction. Ann Intern Med 2004; 141: 693–704
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    Ëå÷åíèå ÈÀÏÔ è ÁÐÀ ñíèæàåò ëåòàëüíîñòü áîëüíûõ ñ ÕÑÍ [70], ÷òî â îòíîøåíèè ÈÀÏÔ çàêðåïëåíî â èíîñòðàííûõ è îòå÷åñòâåííûõ ðåêîìåíäàöèÿõ [71, 72], îäíàêî ìíåíèå îá ýôôåêòèâíîñòè ÁÐÀ è ÊÎÒ íå ñòîëü åäèíîäóøíî. Ïî äàííûì V. Lee è ñîàâò.
    Exact
    [73]
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    , îáðàáîòàâøèõ ðåçóëüòàòû 7 ÐÊÈ, ó áîëüíûõ ñ ÕÑÍ ÊÎÒ íà 23% óìåíüøàëà ÷àñòîòó ãîñïèòàëèçàöèé, íî íå âëèÿëà íà ëåòàëüíîñòü.  èññëåäîâàíèè VALIANT (The Valsartan In Acute Myocardial Infarction) áîëüíûì â ïåðâûå 10 äíåé èíôàðêòà ìèîêàðäà íàçíà÷àëè êàïòîïðèë èëè êàïòîïðèë è âàëñàðòàí.

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Pfeffer MA, McMurray JJ, Velazquez EJ et al. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med 2003; 349: 1893–1906
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    Ïðè äàëüíåéøåì íàáëþäåíèè è â ïîñëåäóþùèå 2 ãîäà ðàçëè÷èé â ÷àñòîòå êàê ïåðâè÷íûõ èñõîäîâ (ëåòàëüíîñòü îò ëþáûõ ïðè÷èí), òàê è âòîðè÷íûõ èñõîäîâ (ÑÑÎ) ìåæäó ãðóïïàìè íå âûÿâëåíî. Íà ôîíå ÊÎÒ ó áîëüíûõ ÷àùå âîçíèêàëè ýïèçîäû ãèïîòåíçèè è ðàçâèâàëàñü äèñôóíêöèÿ ïî÷åê, âïëîòü äî îñòðîé ïî÷å÷íîé íåäîñòàòî÷íîñòè
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    [74]
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    . Âìåñòå ñ òåì, â 2 íåäàâíî îïóáëèêîâàííûõ ìåòà-àíàëèçàõ ïðîäåìîñòðèðîâàíû ïðåèìóùåñòâà ÊÎÒ â ñðàâíåíèè ñ ìîíîòåðàïèåé ÈÀÏÔ èëè ÁÐÀ ó áîëüíûõ Àà [75, 76]. Ïîìèìî íåôðî- è êàðäèîïðîòåêòèâíûõ ñâîéñòâ ÈÀÏÔ è ÁÐÀ, íîâûì ïîêîëåíèÿì ýòèõ ïðåïàðàòîâ ñâîéñòâåííû íåòðàäèöèîííûå ìåõàíèçìû âîçäåéñòâèÿ íà ïàòîëîãè÷åñêèé ïðîöåññ, ðàñøèðÿþùèå ïîêàçàíèÿ ê èõ ïðèìåíåíèþ.

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    Íà ôîíå ÊÎÒ ó áîëüíûõ ÷àùå âîçíèêàëè ýïèçîäû ãèïîòåíçèè è ðàçâèâàëàñü äèñôóíêöèÿ ïî÷åê, âïëîòü äî îñòðîé ïî÷å÷íîé íåäîñòàòî÷íîñòè [74]. Âìåñòå ñ òåì, â 2 íåäàâíî îïóáëèêîâàííûõ ìåòà-àíàëèçàõ ïðîäåìîñòðèðîâàíû ïðåèìóùåñòâà ÊÎÒ â ñðàâíåíèè ñ ìîíîòåðàïèåé ÈÀÏÔ èëè ÁÐÀ ó áîëüíûõ ÀÃ
    Exact
    [75, 76]
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    . Ïîìèìî íåôðî- è êàðäèîïðîòåêòèâíûõ ñâîéñòâ ÈÀÏÔ è ÁÐÀ, íîâûì ïîêîëåíèÿì ýòèõ ïðåïàðàòîâ ñâîéñòâåííû íåòðàäèöèîííûå ìåõàíèçìû âîçäåéñòâèÿ íà ïàòîëîãè÷åñêèé ïðîöåññ, ðàñøèðÿþùèå ïîêàçàíèÿ ê èõ ïðèìåíåíèþ.

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MacKinnon M, Shurraw S, Akbari A et al. Combination therapy with an angiotensin receptor blocker and an ACE inhibitor in proteinuric renal disease: a systematic review of the efficacy and safety data. Am J Kidney Dis 2006; 48: 8–20
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    Íà ôîíå ÊÎÒ ó áîëüíûõ ÷àùå âîçíèêàëè ýïèçîäû ãèïîòåíçèè è ðàçâèâàëàñü äèñôóíêöèÿ ïî÷åê, âïëîòü äî îñòðîé ïî÷å÷íîé íåäîñòàòî÷íîñòè [74]. Âìåñòå ñ òåì, â 2 íåäàâíî îïóáëèêîâàííûõ ìåòà-àíàëèçàõ ïðîäåìîñòðèðîâàíû ïðåèìóùåñòâà ÊÎÒ â ñðàâíåíèè ñ ìîíîòåðàïèåé ÈÀÏÔ èëè ÁÐÀ ó áîëüíûõ ÀÃ
    Exact
    [75, 76]
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    . Ïîìèìî íåôðî- è êàðäèîïðîòåêòèâíûõ ñâîéñòâ ÈÀÏÔ è ÁÐÀ, íîâûì ïîêîëåíèÿì ýòèõ ïðåïàðàòîâ ñâîéñòâåííû íåòðàäèöèîííûå ìåõàíèçìû âîçäåéñòâèÿ íà ïàòîëîãè÷åñêèé ïðîöåññ, ðàñøèðÿþùèå ïîêàçàíèÿ ê èõ ïðèìåíåíèþ.

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Esteban V, Gallego–Delgado Y, Lazaro A et al. Long– term treatment with an ACE inhibitor or an AT1 antagonist avoids hypertension–induced inflammation in the kidney. J Nephrol 2006; 19: 725–731
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    Ïîìèìî íåôðî- è êàðäèîïðîòåêòèâíûõ ñâîéñòâ ÈÀÏÔ è ÁÐÀ, íîâûì ïîêîëåíèÿì ýòèõ ïðåïàðàòîâ ñâîéñòâåííû íåòðàäèöèîííûå ìåõàíèçìû âîçäåéñòâèÿ íà ïàòîëîãè÷åñêèé ïðîöåññ, ðàñøèðÿþùèå ïîêàçàíèÿ ê èõ ïðèìåíåíèþ. Ïëåéîòðîïíûå ýôôåêòû áëîêàòîðîâ ÐÀÀÑ V. Esteban è ñîàâò.
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    [77]
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    â ýêñïåðèìåíòå ïîêàçàëè, ÷òî ó ñïîíòàííî-ãèïåðòåíçèâíûõ êðûñ ëå÷åíèå â òå÷åíèå 48 íåä èíãèáèòîðàìè ÀÏÔ è ÁÐÀ íå òîëüêî ñíèæàåò ïðîòåèíóðèþ, íî è óìåíüøàåò â òêàíè ïî÷åê ÷èñëî ïðîâîñïàëèòåëüíûõ êëåòîê è àêòèâàöèþ íóêëåàðíîãî ôàêòîðà Ê (NF-κÂ) è ýêñïðåññèþ ñîîòâåòñòâóþùèõ ãåíîâ, îñëàáëÿÿ ïðîöåññû âîñïàëåíèÿ â ïî÷å÷íîé òêàíè.

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Татарский БА, Казенова НВ, Серебряков НВ. Прямой локатор ренина при лечении пароксизмальной формы фибрилляции предсердий. Артериальная гипертензия 2010; 16 (1): 74–81
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    íå òîëüêî ñíèæàåò ïðîòåèíóðèþ, íî è óìåíüøàåò â òêàíè ïî÷åê ÷èñëî ïðîâîñïàëèòåëüíûõ êëåòîê è àêòèâàöèþ íóêëåàðíîãî ôàêòîðà Ê (NF-κÂ) è ýêñïðåññèþ ñîîòâåòñòâóþùèõ ãåíîâ, îñëàáëÿÿ ïðîöåññû âîñïàëåíèÿ â ïî÷å÷íîé òêàíè. Âàëñàðòàí, êàê è ïðÿìîé èíãèáèòîð ñåêðåöèè ðåíèíà àëèñêèðåí, ñïîñîáåí ýôôåêòèâíî ïðåäóïðåæäàòü ðåöèäèâû ôèáðèëëÿöèè ïðåäñåðäèé ó áîëüíûõ Àà è äðóãèìè çàáîëåâàíèÿìè ñåðäöà è ñîñóäîâ
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    [78, 79]
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    , óëó÷øàòü ñåêñóàëüíóþ ôóíêöèþ [80, 81], ïîäàâëÿòü ÀÄÔèíäóöèðîâàííóþ àãðåãàöèþ òðîìáîöèòîâ [82], ñíèæàòü â êðîâè áîëüíûõ óðîâåíü âûñîêî÷óâñòâèòåëüíîãî Ñ-ðåàêòèâíîãî áåëêà [83], ÿâëÿþùåãîñÿ ìàðêåðîì âîñïàëèòåëüíîãî ïðîöåññà.

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Jibrini MB, Molnar J, Arora RR. Prevention of atrial fibrillation by way of abrogation of the renin–angiotensin system: a systematic review and meta–analysis. Am J Ther 2008; 15: 36–43
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    íå òîëüêî ñíèæàåò ïðîòåèíóðèþ, íî è óìåíüøàåò â òêàíè ïî÷åê ÷èñëî ïðîâîñïàëèòåëüíûõ êëåòîê è àêòèâàöèþ íóêëåàðíîãî ôàêòîðà Ê (NF-κÂ) è ýêñïðåññèþ ñîîòâåòñòâóþùèõ ãåíîâ, îñëàáëÿÿ ïðîöåññû âîñïàëåíèÿ â ïî÷å÷íîé òêàíè. Âàëñàðòàí, êàê è ïðÿìîé èíãèáèòîð ñåêðåöèè ðåíèíà àëèñêèðåí, ñïîñîáåí ýôôåêòèâíî ïðåäóïðåæäàòü ðåöèäèâû ôèáðèëëÿöèè ïðåäñåðäèé ó áîëüíûõ Àà è äðóãèìè çàáîëåâàíèÿìè ñåðäöà è ñîñóäîâ
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    [78, 79]
    Suffix
    , óëó÷øàòü ñåêñóàëüíóþ ôóíêöèþ [80, 81], ïîäàâëÿòü ÀÄÔèíäóöèðîâàííóþ àãðåãàöèþ òðîìáîöèòîâ [82], ñíèæàòü â êðîâè áîëüíûõ óðîâåíü âûñîêî÷óâñòâèòåëüíîãî Ñ-ðåàêòèâíîãî áåëêà [83], ÿâëÿþùåãîñÿ ìàðêåðîì âîñïàëèòåëüíîãî ïðîöåññà.

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Della Chiesa A, Pfiffner D, Meier B, Hess OM. Sexual activity in hypertensive man. J Hum Hypertens 2003; 17 (8): 515–521
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    Âàëñàðòàí, êàê è ïðÿìîé èíãèáèòîð ñåêðåöèè ðåíèíà àëèñêèðåí, ñïîñîáåí ýôôåêòèâíî ïðåäóïðåæäàòü ðåöèäèâû ôèáðèëëÿöèè ïðåäñåðäèé ó áîëüíûõ ÀÃ è äðóãèìè çàáîëåâàíèÿìè ñåðäöà è ñîñóäîâ [78, 79], óëó÷øàòü ñåêñóàëüíóþ ôóíêöèþ
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    [80, 81]
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    , ïîäàâëÿòü ÀÄÔèíäóöèðîâàííóþ àãðåãàöèþ òðîìáîöèòîâ [82], ñíèæàòü â êðîâè áîëüíûõ óðîâåíü âûñîêî÷óâñòâèòåëüíîãî Ñ-ðåàêòèâíîãî áåëêà [83], ÿâëÿþùåãîñÿ ìàðêåðîì âîñïàëèòåëüíîãî ïðîöåññà. Ó ìûøåé ñ îæèðåíèåì, âñëåäñòâèå ïîòðåáëåíèÿ ðàöèîíà ñ âûñîêèì ñîäåðæàíèåì æèðà, âàëñàðòàí óëó÷øàë òîëåðàíòíîñòü ê ãëþêîçå, ñíèæàë óðîâåíü èíñóëèíà â ñûâîðîòêå, óìåíüøàë âîñïàëèòåëüíûå èçìåíåíèÿ â ãîëîâêå ïîäæåëóäî÷í

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Dusing R. Effect of the angiotensin II antagonist valsartan on sexual function in hypertensive men. Blood Pressure 2003; 12 [Suppl 2]: 29–34
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    Âàëñàðòàí, êàê è ïðÿìîé èíãèáèòîð ñåêðåöèè ðåíèíà àëèñêèðåí, ñïîñîáåí ýôôåêòèâíî ïðåäóïðåæäàòü ðåöèäèâû ôèáðèëëÿöèè ïðåäñåðäèé ó áîëüíûõ ÀÃ è äðóãèìè çàáîëåâàíèÿìè ñåðäöà è ñîñóäîâ [78, 79], óëó÷øàòü ñåêñóàëüíóþ ôóíêöèþ
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    [80, 81]
    Suffix
    , ïîäàâëÿòü ÀÄÔèíäóöèðîâàííóþ àãðåãàöèþ òðîìáîöèòîâ [82], ñíèæàòü â êðîâè áîëüíûõ óðîâåíü âûñîêî÷óâñòâèòåëüíîãî Ñ-ðåàêòèâíîãî áåëêà [83], ÿâëÿþùåãîñÿ ìàðêåðîì âîñïàëèòåëüíîãî ïðîöåññà. Ó ìûøåé ñ îæèðåíèåì, âñëåäñòâèå ïîòðåáëåíèÿ ðàöèîíà ñ âûñîêèì ñîäåðæàíèåì æèðà, âàëñàðòàí óëó÷øàë òîëåðàíòíîñòü ê ãëþêîçå, ñíèæàë óðîâåíü èíñóëèíà â ñûâîðîòêå, óìåíüøàë âîñïàëèòåëüíûå èçìåíåíèÿ â ãîëîâêå ïîäæåëóäî÷í

82
Serebruany V, Popov A, Malinin A et al. Valsartan inhibits platelet activity in different doses in mild to moderate hypertension. Valsartan Inhibits Plateled (VIP) trial. Am Heart J 2006; 151: 92–99
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    Prefix
    Âàëñàðòàí, êàê è ïðÿìîé èíãèáèòîð ñåêðåöèè ðåíèíà àëèñêèðåí, ñïîñîáåí ýôôåêòèâíî ïðåäóïðåæäàòü ðåöèäèâû ôèáðèëëÿöèè ïðåäñåðäèé ó áîëüíûõ ÀÃ è äðóãèìè çàáîëåâàíèÿìè ñåðäöà è ñîñóäîâ [78, 79], óëó÷øàòü ñåêñóàëüíóþ ôóíêöèþ [80, 81], ïîäàâëÿòü ÀÄÔèíäóöèðîâàííóþ àãðåãàöèþ òðîìáîöèòîâ
    Exact
    [82]
    Suffix
    , ñíèæàòü â êðîâè áîëüíûõ óðîâåíü âûñîêî÷óâñòâèòåëüíîãî Ñ-ðåàêòèâíîãî áåëêà [83], ÿâëÿþùåãîñÿ ìàðêåðîì âîñïàëèòåëüíîãî ïðîöåññà. Ó ìûøåé ñ îæèðåíèåì, âñëåäñòâèå ïîòðåáëåíèÿ ðàöèîíà ñ âûñîêèì ñîäåðæàíèåì æèðà, âàëñàðòàí óëó÷øàë òîëåðàíòíîñòü ê ãëþêîçå, ñíèæàë óðîâåíü èíñóëèíà â ñûâîðîòêå, óìåíüøàë âîñïàëèòåëüíûå èçìåíåíèÿ â ãîëîâêå ïîäæåëóäî÷íîé æåëåçû è åå èíôèëüòðàöèþ ìàêðîôàãàìè, ðåäóöèðîâàë â ñ

83
Ridker PM, Danielson E, Rifai N, Glynn RJ. Valsartan, blood pressure reduction, and C–reactive protein: primary report of the Val–MARC trial. Hypertension 2006; 48 (1): 73–79
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    Prefix
    Âàëñàðòàí, êàê è ïðÿìîé èíãèáèòîð ñåêðåöèè ðåíèíà àëèñêèðåí, ñïîñîáåí ýôôåêòèâíî ïðåäóïðåæäàòü ðåöèäèâû ôèáðèëëÿöèè ïðåäñåðäèé ó áîëüíûõ ÀÃ è äðóãèìè çàáîëåâàíèÿìè ñåðäöà è ñîñóäîâ [78, 79], óëó÷øàòü ñåêñóàëüíóþ ôóíêöèþ [80, 81], ïîäàâëÿòü ÀÄÔèíäóöèðîâàííóþ àãðåãàöèþ òðîìáîöèòîâ [82], ñíèæàòü â êðîâè áîëüíûõ óðîâåíü âûñîêî÷óâñòâèòåëüíîãî Ñ-ðåàêòèâíîãî áåëêà
    Exact
    [83]
    Suffix
    , ÿâëÿþùåãîñÿ ìàðêåðîì âîñïàëèòåëüíîãî ïðîöåññà. Ó ìûøåé ñ îæèðåíèåì, âñëåäñòâèå ïîòðåáëåíèÿ ðàöèîíà ñ âûñîêèì ñîäåðæàíèåì æèðà, âàëñàðòàí óëó÷øàë òîëåðàíòíîñòü ê ãëþêîçå, ñíèæàë óðîâåíü èíñóëèíà â ñûâîðîòêå, óìåíüøàë âîñïàëèòåëüíûå èçìåíåíèÿ â ãîëîâêå ïîäæåëóäî÷íîé æåëåçû è åå èíôèëüòðàöèþ ìàêðîôàãàìè, ðåäóöèðîâàë â ñûâîðîòêå ñîäåðæàíèå ïðîâîñïàëèòåëüíûõ öèòîêèíîâ [84].

84
Cole BK, Keller SR, Wu R et al. Valsartan protects pancreatic islets and adipose tissue from inflammatory and metabolic consequences of a high–fat diet in mice. Hypertension 2010; 55 (3): 715–721
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    Ó ìûøåé ñ îæèðåíèåì, âñëåäñòâèå ïîòðåáëåíèÿ ðàöèîíà ñ âûñîêèì ñîäåðæàíèåì æèðà, âàëñàðòàí óëó÷øàë òîëåðàíòíîñòü ê ãëþêîçå, ñíèæàë óðîâåíü èíñóëèíà â ñûâîðîòêå, óìåíüøàë âîñïàëèòåëüíûå èçìåíåíèÿ â ãîëîâêå ïîäæåëóäî÷íîé æåëåçû è åå èíôèëüòðàöèþ ìàêðîôàãàìè, ðåäóöèðîâàë â ñûâîðîòêå ñîäåðæàíèå ïðîâîñïàëèòåëüíûõ öèòîêèíîâ
    Exact
    [84]
    Suffix
    . Íåôðîïîòåêòèâíàÿ àêòèâíîñòü ëîçàðòàíà îòìå÷åíà ïðè èíòåðñòèöèàëüíîì íåôðèòå ó áîëüíîé ñ ìåòèëìàëîíîâîé àöèäåìèåé [85], à ÈÀÏÔ òîðìîçèëè ñíèæåíèå ÑÊÔ ó áîëüíûõ ñ áîëåçíüþ íàêîïëåíèÿ ãëèêîãåíà òèïà 1 [86] è óìåíüøàëè â ñî÷åòàíèè ñ ÁÐÀ ïðîòåèíóðèþ ó áîëüíûõ âîë÷àíî÷íûì íåôðèòîì [87].

85
Ha T–S, Lee J–S, Hong E–J. Delay of renal progression in methylmalonic acidemia using angiotensin II inhibition: a case report. J Nephrol 2008; 21: 793–796
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  1. In-text reference with the coordinate start=22643
    Prefix
    ðàöèîíà ñ âûñîêèì ñîäåðæàíèåì æèðà, âàëñàðòàí óëó÷øàë òîëåðàíòíîñòü ê ãëþêîçå, ñíèæàë óðîâåíü èíñóëèíà â ñûâîðîòêå, óìåíüøàë âîñïàëèòåëüíûå èçìåíåíèÿ â ãîëîâêå ïîäæåëóäî÷íîé æåëåçû è åå èíôèëüòðàöèþ ìàêðîôàãàìè, ðåäóöèðîâàë â ñûâîðîòêå ñîäåðæàíèå ïðîâîñïàëèòåëüíûõ öèòîêèíîâ [84]. Íåôðîïîòåêòèâíàÿ àêòèâíîñòü ëîçàðòàíà îòìå÷åíà ïðè èíòåðñòèöèàëüíîì íåôðèòå ó áîëüíîé ñ ìåòèëìàëîíîâîé àöèäåìèåé
    Exact
    [85]
    Suffix
    , à ÈÀÏÔ òîðìîçèëè ñíèæåíèå ÑÊÔ ó áîëüíûõ ñ áîëåçíüþ íàêîïëåíèÿ ãëèêîãåíà òèïà 1 [86] è óìåíüøàëè â ñî÷åòàíèè ñ ÁÐÀ ïðîòåèíóðèþ ó áîëüíûõ âîë÷àíî÷íûì íåôðèòîì [87]. Íåçàâèñèìî îò áëîêàäû ÀÒ1-ðåöåïòîðîâ êàíäåñàðòàí îáëàäàåò âûðàæåííîé àíòèîêñèäàíòíîé àêòèâíîñòüþ, ÷òî óñèëèâàåò åãî íåôðîïðîòåêòèâíûå ñâîéñòâà [88].

86
Melis D, Parenti G, Gatti R et al. Efficacy of ACE– inhibitor therapy on renal disease in glycogen storage disease type 1: a multicentre retrospective study. Clin Endocrinol 2005; 63: 19–25
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    Íåôðîïîòåêòèâíàÿ àêòèâíîñòü ëîçàðòàíà îòìå÷åíà ïðè èíòåðñòèöèàëüíîì íåôðèòå ó áîëüíîé ñ ìåòèëìàëîíîâîé àöèäåìèåé [85], à ÈÀÏÔ òîðìîçèëè ñíèæåíèå ÑÊÔ ó áîëüíûõ ñ áîëåçíüþ íàêîïëåíèÿ ãëèêîãåíà òèïà 1
    Exact
    [86]
    Suffix
    è óìåíüøàëè â ñî÷åòàíèè ñ ÁÐÀ ïðîòåèíóðèþ ó áîëüíûõ âîë÷àíî÷íûì íåôðèòîì [87]. Íåçàâèñèìî îò áëîêàäû ÀÒ1-ðåöåïòîðîâ êàíäåñàðòàí îáëàäàåò âûðàæåííîé àíòèîêñèäàíòíîé àêòèâíîñòüþ, ÷òî óñèëèâàåò åãî íåôðîïðîòåêòèâíûå ñâîéñòâà [88].

87
Kitamura N, Matsukawa Y, Takei M, Sawada S. Antiproteinuric effect of angiotensin–converting enzyme inhibitors and an angiotensin II receptor blockers in patients with lupus nephritis. J Int Med Res 2009; 37 (3): 892–898
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    Íåôðîïîòåêòèâíàÿ àêòèâíîñòü ëîçàðòàíà îòìå÷åíà ïðè èíòåðñòèöèàëüíîì íåôðèòå ó áîëüíîé ñ ìåòèëìàëîíîâîé àöèäåìèåé [85], à ÈÀÏÔ òîðìîçèëè ñíèæåíèå ÑÊÔ ó áîëüíûõ ñ áîëåçíüþ íàêîïëåíèÿ ãëèêîãåíà òèïà 1 [86] è óìåíüøàëè â ñî÷åòàíèè ñ ÁÐÀ ïðîòåèíóðèþ ó áîëüíûõ âîë÷àíî÷íûì íåôðèòîì
    Exact
    [87]
    Suffix
    . Íåçàâèñèìî îò áëîêàäû ÀÒ1-ðåöåïòîðîâ êàíäåñàðòàí îáëàäàåò âûðàæåííîé àíòèîêñèäàíòíîé àêòèâíîñòüþ, ÷òî óñèëèâàåò åãî íåôðîïðîòåêòèâíûå ñâîéñòâà [88].  èññëåäîâàíèè VALUE (Valsartan Antihypertensive Long-term Use Evaluation) ñ ó÷àñòèåì 15313 áîëüíûõ ñ Àà áûëî ïðîäåìîíñòðèðîâàíî, ÷òî âàëñàðòàí ñíèæàåò ðèñê ðàçâèòèÿ äèàáåòà [89] è ïðîôèëàêòèðóåò ðàçâèòèå èíñóëüòà âíå çàâèñèìîñòè îò äîñòèæåíèÿ

88
Chen S, Ge Y, Si J et al. Candesartan suppresses chronic renal inflammation by a novel antioxidant action independent of AT1R blockade. Kidney Int 2008; 74 (9): 1128–1138
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  1. In-text reference with the coordinate start=22954
    Prefix
    ëîçàðòàíà îòìå÷åíà ïðè èíòåðñòèöèàëüíîì íåôðèòå ó áîëüíîé ñ ìåòèëìàëîíîâîé àöèäåìèåé [85], à ÈÀÏÔ òîðìîçèëè ñíèæåíèå ÑÊÔ ó áîëüíûõ ñ áîëåçíüþ íàêîïëåíèÿ ãëèêîãåíà òèïà 1 [86] è óìåíüøàëè â ñî÷åòàíèè ñ ÁÐÀ ïðîòåèíóðèþ ó áîëüíûõ âîë÷àíî÷íûì íåôðèòîì [87]. Íåçàâèñèìî îò áëîêàäû ÀÒ1-ðåöåïòîðîâ êàíäåñàðòàí îáëàäàåò âûðàæåííîé àíòèîêñèäàíòíîé àêòèâíîñòüþ, ÷òî óñèëèâàåò åãî íåôðîïðîòåêòèâíûå ñâîéñòâà
    Exact
    [88]
    Suffix
    .  èññëåäîâàíèè VALUE (Valsartan Antihypertensive Long-term Use Evaluation) ñ ó÷àñòèåì 15313 áîëüíûõ ñ Àà áûëî ïðîäåìîíñòðèðîâàíî, ÷òî âàëñàðòàí ñíèæàåò ðèñê ðàçâèòèÿ äèàáåòà [89] è ïðîôèëàêòèðóåò ðàçâèòèå èíñóëüòà âíå çàâèñèìîñòè îò äîñòèæåíèÿ öåëåâîãî ÀÄ [90].

89
Kjeldsen SE, McInnes GT, Mancia G et al. Progressive effects of valsartan compared with amlodipine in prevention of diabetes according to categories of diabetogenic risk in hypertensive patients: the VALUE trial. Blood Press 2008; 17: 170–177
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    Íåçàâèñèìî îò áëîêàäû ÀÒ1-ðåöåïòîðîâ êàíäåñàðòàí îáëàäàåò âûðàæåííîé àíòèîêñèäàíòíîé àêòèâíîñòüþ, ÷òî óñèëèâàåò åãî íåôðîïðîòåêòèâíûå ñâîéñòâà [88].  èññëåäîâàíèè VALUE (Valsartan Antihypertensive Long-term Use Evaluation) ñ ó÷àñòèåì 15313 áîëüíûõ ñ Àà áûëî ïðîäåìîíñòðèðîâàíî, ÷òî âàëñàðòàí ñíèæàåò ðèñê ðàçâèòèÿ äèàáåòà
    Exact
    [89]
    Suffix
    è ïðîôèëàêòèðóåò ðàçâèòèå èíñóëüòà âíå çàâèñèìîñòè îò äîñòèæåíèÿ öåëåâîãî ÀÄ [90].  èññëåäîâàíèè SCOPE (n=4964) êàíäåñàðòàí ñíèæàë ðèñê íåôàòàëüíîãî èíñóëüòà íà 27,8% è îáùåãî êîëè÷åñòâà èíñóëüòîâ – íà 23,6% [91], à íàçíà÷åíèå ïðåïàðàòà â îñòðîì ïåðèîäå èíñóëüòà óìåíüøàëî ñìåðòíîñòü áîëüíûõ äî 2,9% ïðîòèâ 7,2% â ñëó÷àå íåäåëüíîé îòñðî÷êè [92].

90
Mochizuki S, Dahlof B, Shimizu M et al. Valsartan in a Japanese population with hypertension and other cardiovascular disease (Jikei Heart Study): a randomised, open–label, blinded endpoint morbidity–mortality study. Lancet 2007; 369: 1431–1439
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  1. In-text reference with the coordinate start=23270
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     èññëåäîâàíèè VALUE (Valsartan Antihypertensive Long-term Use Evaluation) ñ ó÷àñòèåì 15313 áîëüíûõ ñ Àà áûëî ïðîäåìîíñòðèðîâàíî, ÷òî âàëñàðòàí ñíèæàåò ðèñê ðàçâèòèÿ äèàáåòà [89] è ïðîôèëàêòèðóåò ðàçâèòèå èíñóëüòà âíå çàâèñèìîñòè îò äîñòèæåíèÿ öåëåâîãî ÀÄ
    Exact
    [90]
    Suffix
    .  èññëåäîâàíèè SCOPE (n=4964) êàíäåñàðòàí ñíèæàë ðèñê íåôàòàëüíîãî èíñóëüòà íà 27,8% è îáùåãî êîëè÷åñòâà èíñóëüòîâ – íà 23,6% [91], à íàçíà÷åíèå ïðåïàðàòà â îñòðîì ïåðèîäå èíñóëüòà óìåíüøàëî ñìåðòíîñòü áîëüíûõ äî 2,9% ïðîòèâ 7,2% â ñëó÷àå íåäåëüíîé îòñðî÷êè [92].

91
Lithell H, Hansson L, Skoog I et al. The study on cognition and prognosis in the elderly (SCOPE): principal results of a randomized double–blind intervention trial. J Hypertens 2003; 21: 875–886
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  1. In-text reference with the coordinate start=23403
    Prefix
     èññëåäîâàíèè VALUE (Valsartan Antihypertensive Long-term Use Evaluation) ñ ó÷àñòèåì 15313 áîëüíûõ ñ Àà áûëî ïðîäåìîíñòðèðîâàíî, ÷òî âàëñàðòàí ñíèæàåò ðèñê ðàçâèòèÿ äèàáåòà [89] è ïðîôèëàêòèðóåò ðàçâèòèå èíñóëüòà âíå çàâèñèìîñòè îò äîñòèæåíèÿ öåëåâîãî ÀÄ [90].  èññëåäîâàíèè SCOPE (n=4964) êàíäåñàðòàí ñíèæàë ðèñê íåôàòàëüíîãî èíñóëüòà íà 27,8% è îáùåãî êîëè÷åñòâà èíñóëüòîâ – íà 23,6%
    Exact
    [91]
    Suffix
    , à íàçíà÷åíèå ïðåïàðàòà â îñòðîì ïåðèîäå èíñóëüòà óìåíüøàëî ñìåðòíîñòü áîëüíûõ äî 2,9% ïðîòèâ 7,2% â ñëó÷àå íåäåëüíîé îòñðî÷êè [92]. Àíàëîãè÷íûì îáðàçîì âëèÿþò íà ýíäîòåëèàëüíóþ ôóíêöèþ, íàðóøåííóþ ïðè ÀÃ, è äðóãèå ñàðòàíû.

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Schrader J, Luders S, Kulschewski A et al. The ACCESS Study: Evaluation of Acute Candesartan Cilexetil Therapy in Stroke Survivors. Stroke 2003; 34: 1699–1703
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     èññëåäîâàíèè SCOPE (n=4964) êàíäåñàðòàí ñíèæàë ðèñê íåôàòàëüíîãî èíñóëüòà íà 27,8% è îáùåãî êîëè÷åñòâà èíñóëüòîâ – íà 23,6% [91], à íàçíà÷åíèå ïðåïàðàòà â îñòðîì ïåðèîäå èíñóëüòà óìåíüøàëî ñìåðòíîñòü áîëüíûõ äî 2,9% ïðîòèâ 7,2% â ñëó÷àå íåäåëüíîé îòñðî÷êè
    Exact
    [92]
    Suffix
    . Àíàëîãè÷íûì îáðàçîì âëèÿþò íà ýíäîòåëèàëüíóþ ôóíêöèþ, íàðóøåííóþ ïðè ÀÃ, è äðóãèå ñàðòàíû. Ïî äàííûì E. Bragulant è ñîàâò. [93], ëå÷åíèå èðáåðñàðòàíîì ñîïðîâîæäàåòñÿ óëó÷øåíèåì ýíäîòåëèé-çàâèñèìîé âàçîäèëàòàöèè è ñíèæåíèåì â ñûâîðîòêå ýíäîòåëèíà.

93
Bragulat E, Larrousse M, Coca A, de la Sierra A. Effect of long–term irbesartan treatment on endothelium–dependent vasodilation in essential hypertensive patients. Br J Biomed Sci 2003; 60: 191–196
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     èññëåäîâàíèè SCOPE (n=4964) êàíäåñàðòàí ñíèæàë ðèñê íåôàòàëüíîãî èíñóëüòà íà 27,8% è îáùåãî êîëè÷åñòâà èíñóëüòîâ – íà 23,6% [91], à íàçíà÷åíèå ïðåïàðàòà â îñòðîì ïåðèîäå èíñóëüòà óìåíüøàëî ñìåðòíîñòü áîëüíûõ äî 2,9% ïðîòèâ 7,2% â ñëó÷àå íåäåëüíîé îòñðî÷êè [92]. Àíàëîãè÷íûì îáðàçîì âëèÿþò íà ýíäîòåëèàëüíóþ ôóíêöèþ, íàðóøåííóþ ïðè ÀÃ, è äðóãèå ñàðòàíû. Ïî äàííûì E. Bragulant è ñîàâò.
    Exact
    [93]
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    , ëå÷åíèå èðáåðñàðòàíîì ñîïðîâîæäàåòñÿ óëó÷øåíèåì ýíäîòåëèé-çàâèñèìîé âàçîäèëàòàöèè è ñíèæåíèåì â ñûâîðîòêå ýíäîòåëèíà. ÈÀÏÔ, ñîäåðæàùèå ñóëüôãèäðèëüíóþ ãðóïïó, â òîì ÷èñëå çîôåíîïðèë, óëó÷øàþò ýíäîòåëèàëüíóþ ôóíêöèþ.

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Mak IT, Freedman AM, Dickens BF, Weglicki WB. Protective effects of sulfhydryl–containing angiotensin converting enzyme inhibitors against free radical injury in endothelial cells. Biochem Pharmacol 1990; 40(9): 2169–2175
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    Bragulant è ñîàâò. [93], ëå÷åíèå èðáåðñàðòàíîì ñîïðîâîæäàåòñÿ óëó÷øåíèåì ýíäîòåëèé-çàâèñèìîé âàçîäèëàòàöèè è ñíèæåíèåì â ñûâîðîòêå ýíäîòåëèíà. ÈÀÏÔ, ñîäåðæàùèå ñóëüôãèäðèëüíóþ ãðóïïó, â òîì ÷èñëå çîôåíîïðèë, óëó÷øàþò ýíäîòåëèàëüíóþ ôóíêöèþ. Åùå â 1990 ã. Ò. Ìak è ñîàâò.
    Exact
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    íà êóëüòóðå ýíäîòåëèàëüíûõ êëåòîê ïîêàçàëè, ÷òî çîôåíîïðèë ñïîñîáåí ñâÿçûâàòü äî 65% ñâîáîäíûõ ðàäèêàëîâ êèñëîðîäà, èíàêòèâèðóþùèõ NO è âûçûâàþùèõ äèñôóíêöèþ ýíäîòåëèÿ. Ïî äàííûì A. Pasin è ñîàâò. [95], ó áîëüíûõ ñ óìåðåííîé ÀÃ ïðåïàðàò äîñòîâåðíî ñíèæàë ñîäåðæàíèå â êðîâè ïðîäóêòîâ ïåðåêèñíîãî îêèñëåíèÿ è ìîëåêóë àäãåçèè.

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Pasini AF, Garbin U, Uava MC et al. Effect of sulfhydryl and non–sulfhydril angiotensin–converting enzyme inhibitors in endothelial function in essential hypertensive patients. Am J Hypertens 2007; 20 (4): 443–450
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    Ìak è ñîàâò. [94] íà êóëüòóðå ýíäîòåëèàëüíûõ êëåòîê ïîêàçàëè, ÷òî çîôåíîïðèë ñïîñîáåí ñâÿçûâàòü äî 65% ñâîáîäíûõ ðàäèêàëîâ êèñëîðîäà, èíàêòèâèðóþùèõ NO è âûçûâàþùèõ äèñôóíêöèþ ýíäîòåëèÿ. Ïî äàííûì A. Pasin è ñîàâò.
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    , ó áîëüíûõ ñ óìåðåííîé ÀÃ ïðåïàðàò äîñòîâåðíî ñíèæàë ñîäåðæàíèå â êðîâè ïðîäóêòîâ ïåðåêèñíîãî îêèñëåíèÿ è ìîëåêóë àäãåçèè. Óìåíüøàëàñü è ïðîäóêöèÿ ýíäîòåëèíà-1 [96]. ÁÐÀ, íàðÿäó ñî ñòàòèíàìè, ïîêàçàíû è ïðè èíôåêöèîííîé ïàòîëîãèè, òàê êàê ñíèæàþò ëåòàëüíîñòü â ïåðâûå 30 äíåé ó ãîñïèòàëèçèðîâàííûõ áîëüíûõ ñ ñåïñèñîì [97], îäíàêî ÈÀÏÔ è ÁÐÀ îêàçàëèñü íå â ñîñòîÿíèè óìåíüøèòü ðèñê ãîñïèòàëèçàöèé ó ï

96
Evangelista S, Manzini S. Antioxidant and cardioprotective properties of the sulfhydryl angiotensin convesting enzyme inhibitor zofenopril. J Int Med Res 2005; 33: 42–54
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    Ìak è ñîàâò. [94] íà êóëüòóðå ýíäîòåëèàëüíûõ êëåòîê ïîêàçàëè, ÷òî çîôåíîïðèë ñïîñîáåí ñâÿçûâàòü äî 65% ñâîáîäíûõ ðàäèêàëîâ êèñëîðîäà, èíàêòèâèðóþùèõ NO è âûçûâàþùèõ äèñôóíêöèþ ýíäîòåëèÿ. Ïî äàííûì A. Pasin è ñîàâò. [95], ó áîëüíûõ ñ óìåðåííîé ÀÃ ïðåïàðàò äîñòîâåðíî ñíèæàë ñîäåðæàíèå â êðîâè ïðîäóêòîâ ïåðåêèñíîãî îêèñëåíèÿ è ìîëåêóë àäãåçèè. Óìåíüøàëàñü è ïðîäóêöèÿ ýíäîòåëèíà-1
    Exact
    [96]
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    . ÁÐÀ, íàðÿäó ñî ñòàòèíàìè, ïîêàçàíû è ïðè èíôåêöèîííîé ïàòîëîãèè, òàê êàê ñíèæàþò ëåòàëüíîñòü â ïåðâûå 30 äíåé ó ãîñïèòàëèçèðîâàííûõ áîëüíûõ ñ ñåïñèñîì [97], îäíàêî ÈÀÏÔ è ÁÐÀ îêàçàëèñü íå â ñîñòîÿíèè óìåíüøèòü ðèñê ãîñïèòàëèçàöèé ó ïàöèåíòîâ ñ âíåáîëüíè÷íîé ïíåâìîíèåé [98].

97
Mortensen EM, Restrepo M, Copeland L et al. Impact of previous statin and angiotensin II receptor blocker use on mortality in patients hospitalized with sepsis. Pharmacotherapy 2007; 27 (12): 1619–1626
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    Pasin è ñîàâò. [95], ó áîëüíûõ ñ óìåðåííîé ÀÃ ïðåïàðàò äîñòîâåðíî ñíèæàë ñîäåðæàíèå â êðîâè ïðîäóêòîâ ïåðåêèñíîãî îêèñëåíèÿ è ìîëåêóë àäãåçèè. Óìåíüøàëàñü è ïðîäóêöèÿ ýíäîòåëèíà-1 [96]. ÁÐÀ, íàðÿäó ñî ñòàòèíàìè, ïîêàçàíû è ïðè èíôåêöèîííîé ïàòîëîãèè, òàê êàê ñíèæàþò ëåòàëüíîñòü â ïåðâûå 30 äíåé ó ãîñïèòàëèçèðîâàííûõ áîëüíûõ ñ ñåïñèñîì
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    , îäíàêî ÈÀÏÔ è ÁÐÀ îêàçàëèñü íå â ñîñòîÿíèè óìåíüøèòü ðèñê ãîñïèòàëèçàöèé ó ïàöèåíòîâ ñ âíåáîëüíè÷íîé ïíåâìîíèåé [98]. Òàêèì îáðàçîì, êðóã çàáîëåâàíèé, â ñâÿçè ñ êîòîðûìè òåîðåòè÷åñêè è ïðàêòè÷åñêè ïîêàçàíî ïðèìåíåíèå ÈÀÏÔ è ÁÐÀ, íåîáû÷àéíî øèðîê.

98
Etminan M, Zhang B, Fitzgerald M, Brophy JM. Do angiotensin–converting enzyme inhibitors or angiotensin II receptor blockers decrease the risk of hospitalization secondary to community–acquired pneumonia? A nested case–cohort study. Pharmacotherapy 2006; 26: 476–482
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    ÁÐÀ, íàðÿäó ñî ñòàòèíàìè, ïîêàçàíû è ïðè èíôåêöèîííîé ïàòîëîãèè, òàê êàê ñíèæàþò ëåòàëüíîñòü â ïåðâûå 30 äíåé ó ãîñïèòàëèçèðîâàííûõ áîëüíûõ ñ ñåïñèñîì [97], îäíàêî ÈÀÏÔ è ÁÐÀ îêàçàëèñü íå â ñîñòîÿíèè óìåíüøèòü ðèñê ãîñïèòàëèçàöèé ó ïàöèåíòîâ ñ âíåáîëüíè÷íîé ïíåâìîíèåé
    Exact
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    . Òàêèì îáðàçîì, êðóã çàáîëåâàíèé, â ñâÿçè ñ êîòîðûìè òåîðåòè÷åñêè è ïðàêòè÷åñêè ïîêàçàíî ïðèìåíåíèå ÈÀÏÔ è ÁÐÀ, íåîáû÷àéíî øèðîê. Âìåñòå ñ òåì, ðåçóëüòàòû ïðèìåíåíèÿ áëîêàòîðîâ ÐÀÀÑ íå ÿâëÿþòñÿ îäíîçíà÷íî ïîëîæèòåëüíûìè, è äàëåêî íå âî âñåõ ñëó÷àÿõ áëîêàòîðû ÐÀÀÑ ïðåâîñõîäÿò äðóãèå àíòèãèïåðòåíçèâíûå ïðåïàðàòû.

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Hay U, Ludvik B, Gisinger Ch, Schernthaner G. Fehlender Effekt der ACE–Inhibition auf die Makroproteinurie bei diabetischer Nephropathie – eine Langzeitstudie fiber 6 Monate. Schw Med Wochenschr 1988; 118 (5): 165–169
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    Âìåñòå ñ òåì, ðåçóëüòàòû ïðèìåíåíèÿ áëîêàòîðîâ ÐÀÀÑ íå ÿâëÿþòñÿ îäíîçíà÷íî ïîëîæèòåëüíûìè, è äàëåêî íå âî âñåõ ñëó÷àÿõ áëîêàòîðû ÐÀÀÑ ïðåâîñõîäÿò äðóãèå àíòèãèïåðòåíçèâíûå ïðåïàðàòû. Àëüòåðíàòèâíûå íåôðîïðîòåêòîðû Åùå â 1988 ã. U. Hay è ñîàâò.
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    íå íàáëþäàëè ýôôåêòà îò ëå÷åíèÿ êàïòîïðèëîì â òå÷åíèå 6 ìåñ ó 10 áîëüíûõ ÄÍ. Ê êîíöó ïåðèîäà íàáëþäåíèÿ ïðîòåèíóðèÿ ó ïàöèåíòîâ ïîâûñèëàñü ñ 3,7 äî 5,4 ã/ñóò, êðåàòèíèí ñûâîðîòêè âîçðîñ ñ 248 äî 283 ìêìîëü, õîòÿ HbA1c ñíèçèëñÿ ñ 8,3 äî 7,3%.

100
Julius S, Kjeldsen SE, Weber M et al. Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial. Lancet 2004; 363: 2022–2031
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    ÷èñëà 15245 ó÷àñòíèêîâ ñòàðøå 50 ëåò â òå÷åíèå 4,2 ãîäà íàáëþäåíèÿ 1450 äîñòèãëè êîíå÷íîé òî÷êè (ôàòàëüíûé è íåôàòàëüíûé èíôàðêò ìèîêàðäà, âíåçàïíàÿ ñìåðòü, ñåðäå÷íàÿ íåäîñòàòî÷íîñòü è ò.ä.), â òîì ÷èñëå 810 áîëüíûõ, ëå÷èâøèõñÿ âàëñàðòàíîì è 789 ïàöèåíòîâ, ïîëó÷àâøèõ àìëîäèïèí (ñîîòâåòñòâåííî 10,6 è 10,3%). Ó ïîñëåäíèõ ÀÄ áûëî íåñêîëüêî íèæå, ÷åì îáúÿñíÿåòñÿ ðàçëè÷èå â ÷àñòîòå êîíå÷íûõ òî÷åê
    Exact
    [100]
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    . Àâòîðû ïîä÷åðêèâàþò çíà÷åíèå êîíòðîëèðîâàíèÿ Àà â ïðåäóïðåæäåíèè ÑÑÎ, à àíòèãèïåðòåíçèâíûé ïîòåíöèàë âàëñàðòàíà áûë óáåäèòåëüíî ïðîäåìîíñòðèðîâàí â èññëåäîâàíèè PREVIEW. Ó 3194 áîëüíûõ ïîñëå äîáàâëåíèÿ ê ñòàíäàðòíîìó àíòèãèïåðòåíçèâíîìó ëå÷åíèþ íà 90 äíåé âàëñàðòàíà ÀÄ ñíèçèëîñü ñ 154,4/ 91,3 äî 139,0/82,6 ìì ðò ñò. [101].

101
Niepen Patricia Van der, Woestenburg A, Brie H, et al. Effectiveness of Valsartan for Treatment of Hypertension: Patient Profiling and Hierarchical Modeling of Determinants and Outcomes (the PREVIEW Study). Ann Pharmacotherapy; 43 (5): 849–861
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    Àâòîðû ïîä÷åðêèâàþò çíà÷åíèå êîíòðîëèðîâàíèÿ Àà â ïðåäóïðåæäåíèè ÑÑÎ, à àíòèãèïåðòåíçèâíûé ïîòåíöèàë âàëñàðòàíà áûë óáåäèòåëüíî ïðîäåìîíñòðèðîâàí â èññëåäîâàíèè PREVIEW. Ó 3194 áîëüíûõ ïîñëå äîáàâëåíèÿ ê ñòàíäàðòíîìó àíòèãèïåðòåíçèâíîìó ëå÷åíèþ íà 90 äíåé âàëñàðòàíà ÀÄ ñíèçèëîñü ñ 154,4/ 91,3 äî 139,0/82,6 ìì ðò ñò.
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    . Ñîãëàñíî ðåçóëüòàòàì èññëåäîâàíèÿ PEACE (Prevention of Events with Angiotensin-Converting Enzyme Inhibition), ó áîëüíûõ ñî ñòàáèëüíîé ñòåíîêàðäèåé òðàíäîëàïðèë (4 ìã/ñóò) â ñðàâíåíèè ñ ïëàöåáî óìåíüøàë îáùóþ ëåòàëüíîñòü è çàìåäëÿë ïðîãðåññèðîâàíèå ïðè ÑÊÔ < 60 ìë/ìèí, íî íå ó ïàöèåíòîâ ñ íîðìàëüíîé ôóíêöèåé ïî÷åê [102].

102
Solomon SD, Rice MM, Jablonski KA et al. Renal function and effectiveness of angiotensin–converting enzyme inhibitor therapy in patients with chronic stable coronary disease in the prevention of events with ACE inhibition (PEACE) trial. Circulation 2006; 114: 26–31
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    Ñîãëàñíî ðåçóëüòàòàì èññëåäîâàíèÿ PEACE (Prevention of Events with Angiotensin-Converting Enzyme Inhibition), ó áîëüíûõ ñî ñòàáèëüíîé ñòåíîêàðäèåé òðàíäîëàïðèë (4 ìã/ñóò) â ñðàâíåíèè ñ ïëàöåáî óìåíüøàë îáùóþ ëåòàëüíîñòü è çàìåäëÿë ïðîãðåññèðîâàíèå ïðè ÑÊÔ < 60 ìë/ìèí, íî íå ó ïàöèåíòîâ ñ íîðìàëüíîé ôóíêöèåé ïî÷åê
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    . Ó áîëüíûõ ÑÄ òèïà 2 íàçíà÷åíèå öèëàçàïðèëà èëè àìëîäèïèíà îäèíàêîâî çàìåäëÿëî ïàäåíèå ÑÊÔ êàê ó ïàöèåíòîâ ñ íîðìî-, òàê è ÌÀÓ [103]. Ïî P. Zucchelli è ñîàâò. [104], íèôåäèïèí ïðîëîíãèðîâàííîãî äåéñòâèÿ è êàïòîïðèë îêàçûâàëè îäèíàêîâûé òîðìîçÿùèé ýôôåêò íà ñíèæåíèå ÑÊÔ ó áîëüíûõ ñ íà÷àëüíîé ÕÏÍ (êîíöåíòðàöèÿ êðåàòèíèíà â ñûâîðîòêå 2,9 è 3,0 ìã/äë, ïðîòåèíóðèÿ 1,66 è 1,90 ã/ñóò).

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Velussi M, Brocco E, Frigato F et al. Effects of cilazapril and amlodipine on kidney function in hypertensive NIDDM patients. Diabetes 1996; 45: 216–222
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    of Events with Angiotensin-Converting Enzyme Inhibition), ó áîëüíûõ ñî ñòàáèëüíîé ñòåíîêàðäèåé òðàíäîëàïðèë (4 ìã/ñóò) â ñðàâíåíèè ñ ïëàöåáî óìåíüøàë îáùóþ ëåòàëüíîñòü è çàìåäëÿë ïðîãðåññèðîâàíèå ïðè ÑÊÔ < 60 ìë/ìèí, íî íå ó ïàöèåíòîâ ñ íîðìàëüíîé ôóíêöèåé ïî÷åê [102]. Ó áîëüíûõ ÑÄ òèïà 2 íàçíà÷åíèå öèëàçàïðèëà èëè àìëîäèïèíà îäèíàêîâî çàìåäëÿëî ïàäåíèå ÑÊÔ êàê ó ïàöèåíòîâ ñ íîðìî-, òàê è ÌÀÓ
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    . Ïî P. Zucchelli è ñîàâò. [104], íèôåäèïèí ïðîëîíãèðîâàííîãî äåéñòâèÿ è êàïòîïðèë îêàçûâàëè îäèíàêîâûé òîðìîçÿùèé ýôôåêò íà ñíèæåíèå ÑÊÔ ó áîëüíûõ ñ íà÷àëüíîé ÕÏÍ (êîíöåíòðàöèÿ êðåàòèíèíà â ñûâîðîòêå 2,9 è 3,0 ìã/äë, ïðîòåèíóðèÿ 1,66 è 1,90 ã/ñóò).

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Zucchelli P, Zuccala A, Borghi M et al. Long–term comparison between captopril and nifedipine in the progression of renal insufficiency. Kidney Int 1992; 42: 452–458
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    Enzyme Inhibition), ó áîëüíûõ ñî ñòàáèëüíîé ñòåíîêàðäèåé òðàíäîëàïðèë (4 ìã/ñóò) â ñðàâíåíèè ñ ïëàöåáî óìåíüøàë îáùóþ ëåòàëüíîñòü è çàìåäëÿë ïðîãðåññèðîâàíèå ïðè ÑÊÔ < 60 ìë/ìèí, íî íå ó ïàöèåíòîâ ñ íîðìàëüíîé ôóíêöèåé ïî÷åê [102]. Ó áîëüíûõ ÑÄ òèïà 2 íàçíà÷åíèå öèëàçàïðèëà èëè àìëîäèïèíà îäèíàêîâî çàìåäëÿëî ïàäåíèå ÑÊÔ êàê ó ïàöèåíòîâ ñ íîðìî-, òàê è ÌÀÓ [103]. Ïî P. Zucchelli è ñîàâò.
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    , íèôåäèïèí ïðîëîíãèðîâàííîãî äåéñòâèÿ è êàïòîïðèë îêàçûâàëè îäèíàêîâûé òîðìîçÿùèé ýôôåêò íà ñíèæåíèå ÑÊÔ ó áîëüíûõ ñ íà÷àëüíîé ÕÏÍ (êîíöåíòðàöèÿ êðåàòèíèíà â ñûâîðîòêå 2,9 è 3,0 ìã/äë, ïðîòåèíóðèÿ 1,66 è 1,90 ã/ñóò).

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Rahman M, Pressel S, Davis BR et al. Renal outcomes in high–risk hypertensive patients treated with an angiotensin– converting enzyme inhibitor or a calcium channel blocker vs a diuretic: a report from the Antihypertensive and Lipid–Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Arch Intern Med 2005; 165 (8): 936–946
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    Îáîñíîâàííîñòü ñîìíåíèé â îòíîøåíèè îñîáûõ íåôðîïðîòåêòèâíûõ ñâîéñòâ áëîêàòîðîâ ÐÀÀÑ óñóãóáèëàñü ïîñëå îïóáëèêîâàíèÿ ðåçóëüòàòîâ èññëåäîâàíèÿ ALLHAT (The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial), â êîòîðîì íå âûÿâëåíî ïðåèìóùåñòâ ÈÀÏÔ è ÁÐÀ â ïðåäóïðåæäåíèè ÑÑÎ ó áîëüíûõ ñ ÕÁÏ ïî ñðàâíåíèþ ñ äðóãèìè êëàññàìè àíòèãèïåðòåíçèâíûõ ïðåïàðàòîâ
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    [105, 106]
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    . Áîëåå òîãî, íà ôîíå ëå÷åíèÿ ëèçèíîïðèëîì ÒÏÍ ó áîëüíûõ ÄÍ ðàçâèâàëàñü ÷àùå, ÷åì ïðè ïðèìåíåíèè õëîðòàëèäîíà (ó 25 èç 1563 ïðîòèâ 26 èç 2755), à ïî äàííûì S. Suissa è ñîàâò. [107], ó áîëüíûõ ÄÍ ñòàðøå 66 ëåò ïîñëå 3 ëåò ëå÷åíèÿ áëîêàòîðàìè ÐÀÀÑ ÷àñòîòà ÒÏÍ óâåëè÷èëàñü â 4,2 ðàçà.

106
The ALLHAT officers and coordinators for the ALLHAT collaborative research group. Major outcome in high–risk hypertensive patients randomized to angiotensin–converting enzyme inhibitor or calcium channel blоcker vs diuretic. The antihypertensive and lipid–lowering treatment to prevent heart attack trial (ALLHAT). JAMA 2002; 288: 2981–2997
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    Îáîñíîâàííîñòü ñîìíåíèé â îòíîøåíèè îñîáûõ íåôðîïðîòåêòèâíûõ ñâîéñòâ áëîêàòîðîâ ÐÀÀÑ óñóãóáèëàñü ïîñëå îïóáëèêîâàíèÿ ðåçóëüòàòîâ èññëåäîâàíèÿ ALLHAT (The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial), â êîòîðîì íå âûÿâëåíî ïðåèìóùåñòâ ÈÀÏÔ è ÁÐÀ â ïðåäóïðåæäåíèè ÑÑÎ ó áîëüíûõ ñ ÕÁÏ ïî ñðàâíåíèþ ñ äðóãèìè êëàññàìè àíòèãèïåðòåíçèâíûõ ïðåïàðàòîâ
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    . Áîëåå òîãî, íà ôîíå ëå÷åíèÿ ëèçèíîïðèëîì ÒÏÍ ó áîëüíûõ ÄÍ ðàçâèâàëàñü ÷àùå, ÷åì ïðè ïðèìåíåíèè õëîðòàëèäîíà (ó 25 èç 1563 ïðîòèâ 26 èç 2755), à ïî äàííûì S. Suissa è ñîàâò. [107], ó áîëüíûõ ÄÍ ñòàðøå 66 ëåò ïîñëå 3 ëåò ëå÷åíèÿ áëîêàòîðàìè ÐÀÀÑ ÷àñòîòà ÒÏÍ óâåëè÷èëàñü â 4,2 ðàçà.

107
Suissa S, Hutchinson T, Brophy J et al. ACE–inhibitor use and the long–term risk of renal failure in diabetes. Kidney Int 2006; 69: 913–919
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    and Lipid-Lowering Treatment to Prevent Heart Attack Trial), â êîòîðîì íå âûÿâëåíî ïðåèìóùåñòâ ÈÀÏÔ è ÁÐÀ â ïðåäóïðåæäåíèè ÑÑÎ ó áîëüíûõ ñ ÕÁÏ ïî ñðàâíåíèþ ñ äðóãèìè êëàññàìè àíòèãèïåðòåíçèâíûõ ïðåïàðàòîâ [105, 106]. Áîëåå òîãî, íà ôîíå ëå÷åíèÿ ëèçèíîïðèëîì ÒÏÍ ó áîëüíûõ ÄÍ ðàçâèâàëàñü ÷àùå, ÷åì ïðè ïðèìåíåíèè õëîðòàëèäîíà (ó 25 èç 1563 ïðîòèâ 26 èç 2755), à ïî äàííûì S. Suissa è ñîàâò.
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    , ó áîëüíûõ ÄÍ ñòàðøå 66 ëåò ïîñëå 3 ëåò ëå÷åíèÿ áëîêàòîðàìè ÐÀÀÑ ÷àñòîòà ÒÏÍ óâåëè÷èëàñü â 4,2 ðàçà. Ñîãëàñíî T. Jafar è ñîàâò. [48] è M. Kent è ñîàâò. [108], ñðåäè áîëüíûõ ñ íåäèàáåòè÷åñêîé íåôðîïàòèåé (n=1865) íå îòìå÷åíî ÈÀÏÔ-èíäóöèðîâàííîé íåôðîïðîòåêöèè ïðè ïðîòåèíóðèè <0,5 ã/ñóò.

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Kent DM, Jafar TH, Hayward RA et al. Progression risk, urinary protein excretion, and treatment effects of angiotensin–converting enzyme inhibitors in nondiabetic kidney disease. J Am Soc Nephrol 2007; 18 (6): 1959–1965
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    Áîëåå òîãî, íà ôîíå ëå÷åíèÿ ëèçèíîïðèëîì ÒÏÍ ó áîëüíûõ ÄÍ ðàçâèâàëàñü ÷àùå, ÷åì ïðè ïðèìåíåíèè õëîðòàëèäîíà (ó 25 èç 1563 ïðîòèâ 26 èç 2755), à ïî äàííûì S. Suissa è ñîàâò. [107], ó áîëüíûõ ÄÍ ñòàðøå 66 ëåò ïîñëå 3 ëåò ëå÷åíèÿ áëîêàòîðàìè ÐÀÀÑ ÷àñòîòà ÒÏÍ óâåëè÷èëàñü â 4,2 ðàçà. Ñîãëàñíî T. Jafar è ñîàâò. [48] è M. Kent è ñîàâò.
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    , ñðåäè áîëüíûõ ñ íåäèàáåòè÷åñêîé íåôðîïàòèåé (n=1865) íå îòìå÷åíî ÈÀÏÔ-èíäóöèðîâàííîé íåôðîïðîòåêöèè ïðè ïðîòåèíóðèè <0,5 ã/ñóò. Ó 2954 áîëüíûõ ñ ñåðäå÷íî-ñîñóäèñòûìè çàáîëåâàíèÿìè èëè ÑÄ ëå÷åíèå òåëìèñàðòàíîì â äîçå 80 ìã/ñóò â òå÷åíèå 56 ìåñ çíà÷èìî íå âëèÿëî íà ïî÷å÷íûå èñõîäû ïî ñðàâíåíèþ ñ ïëàöåáî (n=2972) – óäâîåíèå êðåàòèíèíà ñûâîðîòêè (56 ïðîòèâ 36) èëè íåîáõîäèìîñòü äèàëèçà (7 ïðîòèâ 10)

109
Mann JF, Schmieder RE, McQueen M et al. Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double–blind, controlled trial. Lancet 2008; 372: 547–553
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    çàáîëåâàíèÿìè èëè ÑÄ ëå÷åíèå òåëìèñàðòàíîì â äîçå 80 ìã/ñóò â òå÷åíèå 56 ìåñ çíà÷èìî íå âëèÿëî íà ïî÷å÷íûå èñõîäû ïî ñðàâíåíèþ ñ ïëàöåáî (n=2972) – óäâîåíèå êðåàòèíèíà ñûâîðîòêè (56 ïðîòèâ 36) èëè íåîáõîäèìîñòü äèàëèçà (7 ïðîòèâ 10). Òåëìèñàðòàí ïðåäóïðåæäàë ïîÿâëåíèå ÌÀÓ ó áîëüøåãî ÷èñëà áîëüíûõ, îäíàêî ó ïîëó÷àâøèõ ÁÐÀ ÑÊÔ ñíèæàëàñü áîëåå áûñòðûìè òåìïàìè (3,2 ïðîòèâ 0,26 ìë/ìèí/1,73 ì3)
    Exact
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    . Ïðè íåêîòîðûõ îáñòîÿòåëüñòâàõ ñíèæåíèå ÑÊÔ íà ôîíå áëîêàäû ÐÀÀÑ íåðåäêî ïðèîáðåòàåò íåîáðàòèìûé õàðàêòåð. Ó 7 ïîæèëûõ (72,3 ãîäà) áîëüíûõ, äëèòåëüíî (25,8 ìåñ) ëå÷èâøèõñÿ ÈÀÏÔ èëè ÁÐÀ, ïîñëå ðåíòãåíîêîíòðàñòíîãî èññëåäîâàíèÿ ÑÊÔ ñíèçèëàñü ñ 45,5 äî 16,6 ìë/ìèí, è 1 ïàöèåíòó ïîòðåáîâàëñÿ äèàëèç.

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    Îïàñíîñòè êîìáèíèðîâàííîãî ïðèìåíåíèÿ áëîêàòîðîâ ÐÀÀÑ Îïàñíîñòè ÊÎÒ íàèáîëåå ÿðêî âûÿâèëèñü â îïóáëèêîâàííûõ â 2008 ã. ðåçóëüòàòàõ èññëåäîâàíèÿ ONTARGET (The Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial)
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    , êîòîðîå ïðîâîäèëîñü â òå÷åíèå 2001–2007 ãã. ñ îõâàòîì 25620 áîëüíûõ â âîçðàñòå ≥ 55 ëåò, ñòðàäàþùèõ àòåðîñêëåðîòè÷åñêèì ïîðàæåíèåì ñîñóäîâ ñ îðãàííûìè ïîðàæåíèÿìè. Ó 38% áûëà ÄÍ è ó 6000 ïàöèåíòîâ – ðàñ÷åòíàÿ ÑÊÔ (MDRD ôîðìóëà) áûëà ìåíåå 60 ìë/ìèí.

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    ÑÊÔ íà ðàìèïðèëå ñíèæàëàñü ìåäëåííåå, ÷åì ïðè ëå÷åíèè òåëìèñàðòàíîì (2,82 ïðîòèâ 4,12 ìë/ìèí), íî ñíèæåíèå îêàçàëîñü íàèáîëåå çíà÷èòåëüíûì íà ÊÎÒ (6,11 ìë/ìèí), òîãäà êàê óâåëè÷åíèå ïðîòåèíóðèè ïî ñðàâíåíèþ ñ èñõîäíîé áûëî áîëåå âûðàæåííûì â ãðóïïå ðàìèïðèëà (+31%) è òåëìèñàðòàíà (+24%) ïî ñðàâíåíèþ ñ ÊÎÒ (+21%)
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    . Òàêèì îáðàçîì, íàèáîëåå ìàñøòàáíîå èññëåäîâàíèå ñ íåôîëîãè÷åñêèì ïðîôèëåì íå ïîäòâåðäèëî îñîáûõ êàðäèî- è íåôðîïðîòåêòèâíûõ ñâîéñòâ ÈÀÏÔ è ÁÐÀ, íî âûñâåòèëî îïàñíîñòè ñî÷åòàííîãî ïðèìåíåíèÿ ýòèõ ïðåïàðàòîâ.

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Onuigbo MA, Onuigbo NT. Does renin–angiotensin aldosterone system blockade exacerbate contrast–induced nephropathy in patients with chronic kidney disease? A prospective 50–month Mayo Clinic study. Ren Fail 2008; 30 (1): 67–72
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    Ó 7 ïîæèëûõ (72,3 ãîäà) áîëüíûõ, äëèòåëüíî (25,8 ìåñ) ëå÷èâøèõñÿ ÈÀÏÔ èëè ÁÐÀ, ïîñëå ðåíòãåíîêîíòðàñòíîãî èññëåäîâàíèÿ ÑÊÔ ñíèçèëàñü ñ 45,5 äî 16,6 ìë/ìèí, è 1 ïàöèåíòó ïîòðåáîâàëñÿ äèàëèç. Ó 2 áîëüíûõ â äàëüíåéøåì ðàçâèëàñü ÒÏÍ, à ó îñòàëüíûõ 5 – ÑÊÔ â òå÷åíèå 19,4 ìåñ íàáëþäåíèÿ óâåëè÷èëàñü äî 41,0 ìë/ìèí
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    . Àâòîðû ïîääåðæèâàþò ðåêîìåíäàöèè îá îòìåíå èíãèáèòîðîâ ÐÀÀÑ ó áîëüíûõ ñ ïëàíèðóåìûì ðåíòãåíîêîíòðàñòíûì èññëåäîâàíèåì. K. Griffin è A. Bidani [111] îòðèöàþò íàëè÷èå ó ÈÀÏÔ è ÁÐÀ îñîáûõ ðåíîïðîòåêòèâíûõ ñâîéñòâ, ñ÷èòàÿ ÷òî ÐÊÈ ÷àñòî ïðîâîäèëèñü â òå÷åíèå íåïðîäîëæèòåëüíîãî âðåìåíè, íà îòíîñèòåëüíî ìîëîäîì êîíòèíãåíòå ñ ïðèìåíåíèåì íåáîëüøèõ äîç ÈÀÏÔ, à îöåíêà ýôôåêòèâíîñòè ïðîèçâîäèëàñü ïî ñóððîã

111
Griffin KA, Bidani AK. Progression of renal disease: renoprotective specificity of renin–angiotensin system blockade. Clin J Am Soc Nephrol 2006; 1:1054–1065
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    Ó 2 áîëüíûõ â äàëüíåéøåì ðàçâèëàñü ÒÏÍ, à ó îñòàëüíûõ 5 – ÑÊÔ â òå÷åíèå 19,4 ìåñ íàáëþäåíèÿ óâåëè÷èëàñü äî 41,0 ìë/ìèí [110]. Àâòîðû ïîääåðæèâàþò ðåêîìåíäàöèè îá îòìåíå èíãèáèòîðîâ ÐÀÀÑ ó áîëüíûõ ñ ïëàíèðóåìûì ðåíòãåíîêîíòðàñòíûì èññëåäîâàíèåì. K. Griffin è A. Bidani
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    îòðèöàþò íàëè÷èå ó ÈÀÏÔ è ÁÐÀ îñîáûõ ðåíîïðîòåêòèâíûõ ñâîéñòâ, ñ÷èòàÿ ÷òî ÐÊÈ ÷àñòî ïðîâîäèëèñü â òå÷åíèå íåïðîäîëæèòåëüíîãî âðåìåíè, íà îòíîñèòåëüíî ìîëîäîì êîíòèíãåíòå ñ ïðèìåíåíèåì íåáîëüøèõ äîç ÈÀÏÔ, à îöåíêà ýôôåêòèâíîñòè ïðîèçâîäèëàñü ïî ñóððîãàòíûì êîíå÷íûì òî÷êàì, òîãäà êàê îñíîâíîå íåôðîïðîòåêòèâíîå äåéñòâèå ÈÀÏÔ è ÁÐÀ ñâÿçàíî ñ èõ àíòèãèïåðòåíçèâíûì ýôôåêòîì.

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Tu rnbull F. Blood Pressure Lowering Treatment Trialists’ Collaboration. Effects of different blood–pressure– lowering regimens on major cardiovascular events: results of prospectively–designed overviews of randomised trials. Lancet 2003; 362: 1527–1535
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    è ÁÐÀ îñîáûõ ðåíîïðîòåêòèâíûõ ñâîéñòâ, ñ÷èòàÿ ÷òî ÐÊÈ ÷àñòî ïðîâîäèëèñü â òå÷åíèå íåïðîäîëæèòåëüíîãî âðåìåíè, íà îòíîñèòåëüíî ìîëîäîì êîíòèíãåíòå ñ ïðèìåíåíèåì íåáîëüøèõ äîç ÈÀÏÔ, à îöåíêà ýôôåêòèâíîñòè ïðîèçâîäèëàñü ïî ñóððîãàòíûì êîíå÷íûì òî÷êàì, òîãäà êàê îñíîâíîå íåôðîïðîòåêòèâíîå äåéñòâèå ÈÀÏÔ è ÁÐÀ ñâÿçàíî ñ èõ àíòèãèïåðòåíçèâíûì ýôôåêòîì. Àíàëîãè÷íûõ âçãëÿäîâ ïðèäåðæèâàþòñÿ F. Turnbull
    Exact
    [112]
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    , T. Jafar è ñîàâò. [113], I. Giatras è ñîàâò. [114], G. Strippoli è ñîàâò. [115]. Îáîáùèâ ðåçóëüòàòû íåñêîëüêèõ ðåïðåçåíòàòèâíûõ èññëåäîâàíèé ïî íåôðîïðîòåêöèè, R. Haynes è ñîàâò. [116] ïðèøëè ê âûâîäó, ÷òî ó áîëüíûõ ñ ìåäëåííî ïðîãðåññèðóþùåé ÕÁÏ è ïðîòåèíóðèåé <0,5 ã/ñóò íåôðîïðîòåêòèâíûé ýôôåêò îò ÈÀÏÔ è ÁÐÀ â ïðîòèâîïîëîæíîñòü íåôðîïàòèÿì, ïðîòåêàþùèì ñ ìàññèâíîé ïðîòåèíóðèåé, íåçíà÷èòåëåí.

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Jafar TH, Schmid CH, Landa M et al. Angiotensin– converting enzyme inhibitors and progression of nondiabetic renal disease. A meta–analysis of patient–level data. Ann Intern Med 2001; 135: 73–87
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    ñâîéñòâ, ñ÷èòàÿ ÷òî ÐÊÈ ÷àñòî ïðîâîäèëèñü â òå÷åíèå íåïðîäîëæèòåëüíîãî âðåìåíè, íà îòíîñèòåëüíî ìîëîäîì êîíòèíãåíòå ñ ïðèìåíåíèåì íåáîëüøèõ äîç ÈÀÏÔ, à îöåíêà ýôôåêòèâíîñòè ïðîèçâîäèëàñü ïî ñóððîãàòíûì êîíå÷íûì òî÷êàì, òîãäà êàê îñíîâíîå íåôðîïðîòåêòèâíîå äåéñòâèå ÈÀÏÔ è ÁÐÀ ñâÿçàíî ñ èõ àíòèãèïåðòåíçèâíûì ýôôåêòîì. Àíàëîãè÷íûõ âçãëÿäîâ ïðèäåðæèâàþòñÿ F. Turnbull [112], T. Jafar è ñîàâò.
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    , I. Giatras è ñîàâò. [114], G. Strippoli è ñîàâò. [115]. Îáîáùèâ ðåçóëüòàòû íåñêîëüêèõ ðåïðåçåíòàòèâíûõ èññëåäîâàíèé ïî íåôðîïðîòåêöèè, R. Haynes è ñîàâò. [116] ïðèøëè ê âûâîäó, ÷òî ó áîëüíûõ ñ ìåäëåííî ïðîãðåññèðóþùåé ÕÁÏ è ïðîòåèíóðèåé <0,5 ã/ñóò íåôðîïðîòåêòèâíûé ýôôåêò îò ÈÀÏÔ è ÁÐÀ â ïðîòèâîïîëîæíîñòü íåôðîïàòèÿì, ïðîòåêàþùèì ñ ìàññèâíîé ïðîòåèíóðèåé, íåçíà÷èòåëåí.

114
Giatras I, Lau J, Levey AS. Angiotensin–converting– enzyme inhibition and progressive renal disease study group. Effects of angiotensin–converting enzyme inhibits on the progression of nondiabetic renal disease: meta–analysis of randomised trials. Ann Intern Med 1997; 127: 337–345
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    ÐÊÈ ÷àñòî ïðîâîäèëèñü â òå÷åíèå íåïðîäîëæèòåëüíîãî âðåìåíè, íà îòíîñèòåëüíî ìîëîäîì êîíòèíãåíòå ñ ïðèìåíåíèåì íåáîëüøèõ äîç ÈÀÏÔ, à îöåíêà ýôôåêòèâíîñòè ïðîèçâîäèëàñü ïî ñóððîãàòíûì êîíå÷íûì òî÷êàì, òîãäà êàê îñíîâíîå íåôðîïðîòåêòèâíîå äåéñòâèå ÈÀÏÔ è ÁÐÀ ñâÿçàíî ñ èõ àíòèãèïåðòåíçèâíûì ýôôåêòîì. Àíàëîãè÷íûõ âçãëÿäîâ ïðèäåðæèâàþòñÿ F. Turnbull [112], T. Jafar è ñîàâò. [113], I. Giatras è ñîàâò.
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    , G. Strippoli è ñîàâò. [115]. Îáîáùèâ ðåçóëüòàòû íåñêîëüêèõ ðåïðåçåíòàòèâíûõ èññëåäîâàíèé ïî íåôðîïðîòåêöèè, R. Haynes è ñîàâò. [116] ïðèøëè ê âûâîäó, ÷òî ó áîëüíûõ ñ ìåäëåííî ïðîãðåññèðóþùåé ÕÁÏ è ïðîòåèíóðèåé <0,5 ã/ñóò íåôðîïðîòåêòèâíûé ýôôåêò îò ÈÀÏÔ è ÁÐÀ â ïðîòèâîïîëîæíîñòü íåôðîïàòèÿì, ïðîòåêàþùèì ñ ìàññèâíîé ïðîòåèíóðèåé, íåçíà÷èòåëåí.

115
Strippoli GFM, Craig M, Deeks JJ et al. Effects of angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists on mortality and renal outcomes in diabetic nephropathy: systematic review. BMJ 2004; 329: 828
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    íåïðîäîëæèòåëüíîãî âðåìåíè, íà îòíîñèòåëüíî ìîëîäîì êîíòèíãåíòå ñ ïðèìåíåíèåì íåáîëüøèõ äîç ÈÀÏÔ, à îöåíêà ýôôåêòèâíîñòè ïðîèçâîäèëàñü ïî ñóððîãàòíûì êîíå÷íûì òî÷êàì, òîãäà êàê îñíîâíîå íåôðîïðîòåêòèâíîå äåéñòâèå ÈÀÏÔ è ÁÐÀ ñâÿçàíî ñ èõ àíòèãèïåðòåíçèâíûì ýôôåêòîì. Àíàëîãè÷íûõ âçãëÿäîâ ïðèäåðæèâàþòñÿ F. Turnbull [112], T. Jafar è ñîàâò. [113], I. Giatras è ñîàâò. [114], G. Strippoli è ñîàâò.
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    . Îáîáùèâ ðåçóëüòàòû íåñêîëüêèõ ðåïðåçåíòàòèâíûõ èññëåäîâàíèé ïî íåôðîïðîòåêöèè, R. Haynes è ñîàâò. [116] ïðèøëè ê âûâîäó, ÷òî ó áîëüíûõ ñ ìåäëåííî ïðîãðåññèðóþùåé ÕÁÏ è ïðîòåèíóðèåé <0,5 ã/ñóò íåôðîïðîòåêòèâíûé ýôôåêò îò ÈÀÏÔ è ÁÐÀ â ïðîòèâîïîëîæíîñòü íåôðîïàòèÿì, ïðîòåêàþùèì ñ ìàññèâíîé ïðîòåèíóðèåé, íåçíà÷èòåëåí.

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Haynes R, Mason Ph, Rahimi K, Landray M. Dual blockade of the renin–angiotensin system: are two better than one? NDT 2009; 24: 3602–3607
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    Àíàëîãè÷íûõ âçãëÿäîâ ïðèäåðæèâàþòñÿ F. Turnbull [112], T. Jafar è ñîàâò. [113], I. Giatras è ñîàâò. [114], G. Strippoli è ñîàâò. [115]. Îáîáùèâ ðåçóëüòàòû íåñêîëüêèõ ðåïðåçåíòàòèâíûõ èññëåäîâàíèé ïî íåôðîïðîòåêöèè, R. Haynes è ñîàâò.
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    ïðèøëè ê âûâîäó, ÷òî ó áîëüíûõ ñ ìåäëåííî ïðîãðåññèðóþùåé ÕÁÏ è ïðîòåèíóðèåé <0,5 ã/ñóò íåôðîïðîòåêòèâíûé ýôôåêò îò ÈÀÏÔ è ÁÐÀ â ïðîòèâîïîëîæíîñòü íåôðîïàòèÿì, ïðîòåêàþùèì ñ ìàññèâíîé ïðîòåèíóðèåé, íåçíà÷èòåëåí.

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Staessen JA, Wang J. Do ancillary properties of antihypertensive drugs explain the outcome results of recent trials? J Nephrol 2002; 15: 422–427
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    ê âûâîäó, ÷òî ó áîëüíûõ ñ ìåäëåííî ïðîãðåññèðóþùåé ÕÁÏ è ïðîòåèíóðèåé <0,5 ã/ñóò íåôðîïðîòåêòèâíûé ýôôåêò îò ÈÀÏÔ è ÁÐÀ â ïðîòèâîïîëîæíîñòü íåôðîïàòèÿì, ïðîòåêàþùèì ñ ìàññèâíîé ïðîòåèíóðèåé, íåçíà÷èòåëåí. Ñ ó÷åòîì âîçìîæíûõ îñëîæíåíèé îò áëîêàòîðîâ ÐÀÀÑ òàêèì áîëüíûì ïîêàçàíà òåðàïèÿ äðóãèìè àíòèãèïåðòåíçèâíûìè ïðåïàðàòàìè, íî ñ óñëîâèåì äîñòèæåíèÿ öåëåâûõ çíà÷åíèé ÀÄ. J. Staessen è J. Wang
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    ïðîâåëè ìåòà-àíàëèç 27 èññëåäîâàíèé (n=136124) è ïðèøëè ê çàêëþ÷åíèþ, ÷òî íåôðîïðîòåêòèâíûå ñâîéñòâà ÈÀÏÔ, êàê è äðóãèõ ïðåïàðàòîâ, îáóñëîâëåíû ñïîñîáíîñòüþ ñíèæàòü ÀÄ. Êàêèìè-ëèáî äîïîëíèòåëüíûìè íåôðîïðîòåêòèâíûìè êà÷åñòâàìè ÈÀÏÔ è ÁÐÀ íå îáëàäàþò.

118
Phillips CO, Kashani A, Ko DK et al. Adverse effects of combination of angiotensin II receptor blockers plus angiotensin–converting enzyme inhibitors for left ventricular dysfunction: A quantitative review of data from randomized clinical trials. Arch Intern Med 2007; 167: 1930–1936
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    Wang [117] ïðîâåëè ìåòà-àíàëèç 27 èññëåäîâàíèé (n=136124) è ïðèøëè ê çàêëþ÷åíèþ, ÷òî íåôðîïðîòåêòèâíûå ñâîéñòâà ÈÀÏÔ, êàê è äðóãèõ ïðåïàðàòîâ, îáóñëîâëåíû ñïîñîáíîñòüþ ñíèæàòü ÀÄ. Êàêèìè-ëèáî äîïîëíèòåëüíûìè íåôðîïðîòåêòèâíûìè êà÷åñòâàìè ÈÀÏÔ è ÁÐÀ íå îáëàäàþò. Ch. Phyllips è ñîàâò.
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    ïðîâåëè ìåòààíàëèç 4 êðóïíûõ (áîëåå 500 ó÷àñòíèêîâ) èññëåäîâàíèé ñ ó÷àñòèåì 17337 áîëüíûõ ñ ÕÑÍ è ÎÈÌ ñ ëåâîæåëóäî÷êîâîé íåäîñòàòî÷íîñòüþ ïðè ñðîêàõ íàáëþäåíèÿ áîëåå 25 ìåñ. 50% áîëüíûõ ëå÷èëèñü ÈÀÏÔ, à ó îñòàëüíûõ – ïðèìåíÿëè ÊÎÒ.

119
The ONTARGET Investigators. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 2008; 358: 1547–1559
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    Íå âûÿâëåíî ðàçëè÷èé â ëåòàëüíîñòè ïî ãðóïïàì, îäíàêî ó 29% ïàöèåíòîâ íà ÊÎÒ ïðèøëîñü ïðåðâàòü ëå÷åíèå èç-çà ðàçëè÷íûõ îñëîæíåíèé, â ïåðâóþ î÷åðåäü, ãèïîòåíçèè ïî ñðàâíåíèþ ñ 23% íà ìîíîòåðàïèè. Ïðîöåíò ãèïîòåíçèâíûõ ýïèçîäîâ ñîñòàâëÿë äëÿ ðàìèïðèëà 1,7%, òåëìèñàðòàíà – 2,6%, ÊÎÒ – 4,8%
    Exact
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    . Öèôðû ÀÄ ó áîëüíûõ, ïîëó÷àâøèõ òåëìèñàðòàí è ÊÎÒ, áûëè íà 0,9/0,6 è 2,4/1,4 ìì ðò ñò. íèæå, ÷åì ó ïàöèåíòîâ, ëå÷èâøèõñÿ ðàìèïðèëîì. Àíòèãèïåðòåíçèâíîå ëå÷åíèå íå îêàçûâàëî âëèÿíèÿ íà ÷àñòîòó ôàòàëüíîãî è íåôàòàëüíîãî èíôàðêòà ìèîêàðäà è ñåðäå÷íî-ñîñóäèñòóþ ëåòàëüíîñòü, êîòîðàÿ äàæå íåñêîëüêî óâåëè÷èëàñü, â òî âðåìÿ êàê ïðè ñèñòîëè÷åñêîì ÀÄ<130 ìì ðò ñò. óìåíüøàëîñü ÷èñëî èíñóëüòîâ [120].

120
Sleight P, Redon J, Verdecchia P et al. Prognostic value of blood pressure in patients with high vascular risk in the Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial study. J Hypertens 2009; 27: 1360–1369
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    Àíòèãèïåðòåíçèâíîå ëå÷åíèå íå îêàçûâàëî âëèÿíèÿ íà ÷àñòîòó ôàòàëüíîãî è íåôàòàëüíîãî èíôàðêòà ìèîêàðäà è ñåðäå÷íî-ñîñóäèñòóþ ëåòàëüíîñòü, êîòîðàÿ äàæå íåñêîëüêî óâåëè÷èëàñü, â òî âðåìÿ êàê ïðè ñèñòîëè÷åñêîì ÀÄ<130 ìì ðò ñò. óìåíüøàëîñü ÷èñëî èíñóëüòîâ
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    . Òàêèì îáðàçîì, ÊÎÒ íå îêàçûâàëà êàðäèîïðîòåêòèâíîãî ýôôåêòà, âêëþ÷àÿ áîëüíûõ ñ íàðóøåííîé ôóíêöèåé ïî÷åê è ïðîòåèíóðèåé, è îíè óìèðàëè îò ñåðäå÷íî-ñîñóäèñòûõ îñëîæíåíèé, íå äîæèâàÿ äî ÒÏÍ. ×èñëî ïåðâè÷íûõ êîìïîçèòíûõ èñõîäîâ (êîíå÷íûõ òî÷åê) â ãðóïïå òåëìèñàðòàíà (1147; 13,4%) è ðàìèïðèëà (1150; 13,5%) íå ðàçëè÷àëîñü, íî áûëî âûøå íà ôîíå ÊÎÒ (1233; 14,5%).

121
Centers for Disease Control and Prevention (CDC): Prevalence of chronic kidney disease and associated risk factors – United States, 1999–2004. Morb Mortal Wkly Rep 2007; 56: 161–165
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    Òàêèì îáðàçîì, íàèáîëåå ìàñøòàáíîå èññëåäîâàíèå ñ íåôîëîãè÷åñêèì ïðîôèëåì íå ïîäòâåðäèëî îñîáûõ êàðäèî- è íåôðîïðîòåêòèâíûõ ñâîéñòâ ÈÀÏÔ è ÁÐÀ, íî âûñâåòèëî îïàñíîñòè ñî÷åòàííîãî ïðèìåíåíèÿ ýòèõ ïðåïàðàòîâ. Ðåçóëüòàòû ONTARGET â îïðåäåëåííîé ñòåïåíè îêàçàëèñü ñîçâó÷íûìè äàííûì CDC (Centers for Disease Control and Prevention, 2007; 2008)
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    , ñîãëàñíî êîòîðûì â ÑØÀ â ïîñëåäíèå 2 äåñÿòèëåòèÿ, íåñìîòðÿ íà ïðèìåíåíèå ó 80% áîëüíûõ ÑÄ ÈÀÏÔ, ÷àñòîòà ÕÁÏ, âêëþ÷àÿ îñòðóþ ïî÷å÷íóþ íåäîñòàòî÷íîñòü íà ôîíå ÕÁÏ, è ÒÏÍ óâåëè÷èâàëàñü òåìïàìè, îïåðåæàþùèìè ïîÿâëåíèå íîâûõ ñëó÷àåâ ÑÄ è ÄÍ.

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Centers for Disease Control and Prevention (CDC): Hospitalization discharge diagnoses for kidney disease – United States, 1980–2005. Morb Mortal Wkly Rep 2008; 57: 309–312
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    Òàêèì îáðàçîì, íàèáîëåå ìàñøòàáíîå èññëåäîâàíèå ñ íåôîëîãè÷åñêèì ïðîôèëåì íå ïîäòâåðäèëî îñîáûõ êàðäèî- è íåôðîïðîòåêòèâíûõ ñâîéñòâ ÈÀÏÔ è ÁÐÀ, íî âûñâåòèëî îïàñíîñòè ñî÷åòàííîãî ïðèìåíåíèÿ ýòèõ ïðåïàðàòîâ. Ðåçóëüòàòû ONTARGET â îïðåäåëåííîé ñòåïåíè îêàçàëèñü ñîçâó÷íûìè äàííûì CDC (Centers for Disease Control and Prevention, 2007; 2008)
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    , ñîãëàñíî êîòîðûì â ÑØÀ â ïîñëåäíèå 2 äåñÿòèëåòèÿ, íåñìîòðÿ íà ïðèìåíåíèå ó 80% áîëüíûõ ÑÄ ÈÀÏÔ, ÷àñòîòà ÕÁÏ, âêëþ÷àÿ îñòðóþ ïî÷å÷íóþ íåäîñòàòî÷íîñòü íà ôîíå ÕÁÏ, è ÒÏÍ óâåëè÷èâàëàñü òåìïàìè, îïåðåæàþùèìè ïîÿâëåíèå íîâûõ ñëó÷àåâ ÑÄ è ÄÍ.

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Epstein M. Re–examination RAS–blocking treatment regimens for abrogating progression of chronic kidney disease. Nat Clin Pract Nephrol 2009; 5: 12–13
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    Äàííûå èññëåäîâàíèÿ ONTARGET âûçâàëè îæèâëåííóþ äèñêóññèþ. Íåäîñòàòêàìè èññëåäîâàíèÿ ñ÷èòàþò íåðåïðåçåíòàòèâíîå êîëè÷åñòâî áîëüíûõ ñ íåôðîïàòèÿìè, ïðîòåêàþùèìè ñ ïðîòåèíóðèåé >1,0 ã/ñóò (≈1000 ó÷àñòíèêîâ), è ïàöèåíòîâ ñ ÄÍ (≈700 ó÷àñòíèêîâ)
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    . Òîëüêî ó 98 áîëüíûõ (0,4%) ðàçâèëàñü ÒÏÍ, âñòðå÷àåìîñòü êîòîðîé íå ðàçëè÷àëàñü ïî ðàíäîìèçèðîâàííûì ãðóïïàì è íå ïðåâûøàëà åå ÷àñòîòó â îáùåé ïîïóëÿöèè è ó áîëüíûõ ÑÄ è Àà [124]. Íåîáõîäèìîñòü áîëåå ÷àñòîãî ïðèìåíåíèÿ îñòðîãî äèàëèçà ó áîëüíûõ íà ÊÎÒ (ó 0,33% ïàöèåíòîâ ïðîòèâ 0,23% è 0,15%) îáúÿñíÿþò âîçíèêíîâåíèåì ãèïîïåðôóçèè ïî÷åê íà ôîíå áîëåå âûðàæåííîãî ñíèæåíèÿ ÀÄ, ãèïîâîëåìèè èëè

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    Íåîäíîçíà÷íîé ÿâëÿåòñÿ òðàêòîâêà èçìåíåíèé ÑÊÔ è ïðîòåèíóðèè. Ïîñëåäíÿÿ â áîëüøåé ñòåïåíè ñíèæàëàñü ó áîëüíûõ íà ÊÎÒ, íî îäíîâðåìåííî ó ïàöèåíòîâ ýòîé ãðóïïû îòìå÷àëèñü áîëåå áûñòðûå òåìïû ïàäåíèÿ ÑÊÔ. Ýòî ïîçâîëèëî M. Epstein
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    ñäåëàòü çàêëþ÷åíèå, ÷òî óìåíüøåíèå ïðîòåèíóðèè íå ñâèäåòåëüñòâóåò îá óëó÷øåíèè ôóíêöèè ïî÷åê.  òî æå âðåìÿ, ïî ìíåíèþ P. Ruggenenti è G. Remuzzi [124], óìåíüøåíèå ïðîòåèíóðèè ÿâëÿåòñÿ âàæíåéøèì ìàðêåðîì ñòàáèëèçàöèè ïî÷å÷íîãî âîñïàëåíèÿ è ñïîñîáñòâóåò çàìåäëåíèþ ïðîãðåññèðîâàíèÿ íåôðîïàòèé.

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Ruggenenti P, Remuzzi G. Is the ONTARGET renal substudy actually off target? Nat Rev Nephrol 2009; 5: 436–437
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    Íåäîñòàòêàìè èññëåäîâàíèÿ ñ÷èòàþò íåðåïðåçåíòàòèâíîå êîëè÷åñòâî áîëüíûõ ñ íåôðîïàòèÿìè, ïðîòåêàþùèìè ñ ïðîòåèíóðèåé >1,0 ã/ñóò (≈1000 ó÷àñòíèêîâ), è ïàöèåíòîâ ñ ÄÍ (≈700 ó÷àñòíèêîâ) [123]. Òîëüêî ó 98 áîëüíûõ (0,4%) ðàçâèëàñü ÒÏÍ, âñòðå÷àåìîñòü êîòîðîé íå ðàçëè÷àëàñü ïî ðàíäîìèçèðîâàííûì ãðóïïàì è íå ïðåâûøàëà åå ÷àñòîòó â îáùåé ïîïóëÿöèè è ó áîëüíûõ ÑÄ è ÀÃ
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    . Íåîáõîäèìîñòü áîëåå ÷àñòîãî ïðèìåíåíèÿ îñòðîãî äèàëèçà ó áîëüíûõ íà ÊÎÒ (ó 0,33% ïàöèåíòîâ ïðîòèâ 0,23% è 0,15%) îáúÿñíÿþò âîçíèêíîâåíèåì ãèïîïåðôóçèè ïî÷åê íà ôîíå áîëåå âûðàæåííîãî ñíèæåíèÿ ÀÄ, ãèïîâîëåìèè èëè ñîïóòñòâóþùåé èøåìè÷åñêîé áîëåçíè ïî÷åê.

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    Ïîñëåäíÿÿ â áîëüøåé ñòåïåíè ñíèæàëàñü ó áîëüíûõ íà ÊÎÒ, íî îäíîâðåìåííî ó ïàöèåíòîâ ýòîé ãðóïïû îòìå÷àëèñü áîëåå áûñòðûå òåìïû ïàäåíèÿ ÑÊÔ. Ýòî ïîçâîëèëî M. Epstein [123] ñäåëàòü çàêëþ÷åíèå, ÷òî óìåíüøåíèå ïðîòåèíóðèè íå ñâèäåòåëüñòâóåò îá óëó÷øåíèè ôóíêöèè ïî÷åê.  òî æå âðåìÿ, ïî ìíåíèþ P. Ruggenenti è G. Remuzzi
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    , óìåíüøåíèå ïðîòåèíóðèè ÿâëÿåòñÿ âàæíåéøèì ìàðêåðîì ñòàáèëèçàöèè ïî÷å÷íîãî âîñïàëåíèÿ è ñïîñîáñòâóåò çàìåäëåíèþ ïðîãðåññèðîâàíèÿ íåôðîïàòèé. Íåñìîòðÿ íà îòìå÷åííûå íåäî÷åòû, èññëåäîâàíèå ONTARGET ïîçâîëÿåò ñäåëàòü âûâîäû, ÷òî ìàêñèìàëüíàÿ áëîêàäà ÐÀÀÑ íà ôîíå ÊÎÒ ìîæåò óõóäøèòü ôóíêöèþ ïî÷åê ó áîëüíûõ ñ âûñîêèì ñîñóäèñòûì ðèñêîì, è åå íàçíà÷åíèå íå îïðàâäàíî ïðè ïðîòåèíóðèè <1,0 ã/ñóò.

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Abutaleb N. ONTARGET should not be over interpreted. NDT 2010; 25 (1): 44–47
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    Ñ ó÷åòîì íà÷àëüíîãî ñíèæåíèÿ ÑÊÔ ïîñëå íàçíà÷åíèÿ áëîêàòîðîâ ÐÀÀÑ äàëüíåéøåå ñíèæåíèå çà ïåðèîä íàáëþäåíèÿ ñîñòàâèëî 1,17 ìë/ìèí äëÿ áîëüíûõ, ëå÷èâøèõñÿ ðàìèïðèëîì, 2,06 äëÿ ïàöèåíòîâ, ïîëó÷àâøèõ òåëìèñàðòàí, è 2,49 – íà ôîíå ÊÎÒ.  ñðåäíåì ÑÊÔ ïî ãðóïïàì óìåíüøàëàñü íà 0,25, 0,44 è 0,53 ìë/ìèí/ãîä, ÷òî íå èìååò êëèíè÷åñêîãî çíà÷åíèÿ ñ ó÷åòîì îøèáêè ìåòîäîâ îïðåäåëåíèÿ êðåàòèíèíà ñûâîðîòêè
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    [125]
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    . Ñëåäóåò ó÷èòûâàòü, ÷òî ëå÷åíèå áëîêàòîðàìè ÐÀÀÑ ñïîñîáñòâóåò ñîõðàíåíèþ ó áîëüíûõ ìûøå÷íîé ìàññû, âëèÿþùåé íà óðîâåíü êðåàòèíèíà [126]. Áëàãîïðèÿòíîå âëèÿíèå áëîêàòîðîâ ÐÀÀÑ íà ìûøå÷íóþ òêàíü ïîäòâåðæäåíî è â ýêñïåðèìåíòå [127].

126
D i Bari M, van de Poll–Franse L, Onder G et al. Antihypertensive medications and differences in muscle mass in older persons: the health, aging and body composition study. J Am Geriatr Soc 2004; 52: 961–996
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     ñðåäíåì ÑÊÔ ïî ãðóïïàì óìåíüøàëàñü íà 0,25, 0,44 è 0,53 ìë/ìèí/ãîä, ÷òî íå èìååò êëèíè÷åñêîãî çíà÷åíèÿ ñ ó÷åòîì îøèáêè ìåòîäîâ îïðåäåëåíèÿ êðåàòèíèíà ñûâîðîòêè [125]. Ñëåäóåò ó÷èòûâàòü, ÷òî ëå÷åíèå áëîêàòîðàìè ÐÀÀÑ ñïîñîáñòâóåò ñîõðàíåíèþ ó áîëüíûõ ìûøå÷íîé ìàññû, âëèÿþùåé íà óðîâåíü êðåàòèíèíà
    Exact
    [126]
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    . Áëàãîïðèÿòíîå âëèÿíèå áëîêàòîðîâ ÐÀÀÑ íà ìûøå÷íóþ òêàíü ïîäòâåðæäåíî è â ýêñïåðèìåíòå [127]. Íåîäíîçíà÷íîé ÿâëÿåòñÿ òðàêòîâêà èçìåíåíèé ÑÊÔ è ïðîòåèíóðèè. Ïîñëåäíÿÿ â áîëüøåé ñòåïåíè ñíèæàëàñü ó áîëüíûõ íà ÊÎÒ, íî îäíîâðåìåííî ó ïàöèåíòîâ ýòîé ãðóïïû îòìå÷àëèñü áîëåå áûñòðûå òåìïû ïàäåíèÿ ÑÊÔ.

127
Tobili JE, Stella I, Mazza ON et al. The effect of different anti hypertensive drugs on cavernous tissue in experimental chronic renal insufficiency. J Nephrol 2006; 19 (4): 419–428
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    Ñëåäóåò ó÷èòûâàòü, ÷òî ëå÷åíèå áëîêàòîðàìè ÐÀÀÑ ñïîñîáñòâóåò ñîõðàíåíèþ ó áîëüíûõ ìûøå÷íîé ìàññû, âëèÿþùåé íà óðîâåíü êðåàòèíèíà [126]. Áëàãîïðèÿòíîå âëèÿíèå áëîêàòîðîâ ÐÀÀÑ íà ìûøå÷íóþ òêàíü ïîäòâåðæäåíî è â ýêñïåðèìåíòå
    Exact
    [127]
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    . Íåîäíîçíà÷íîé ÿâëÿåòñÿ òðàêòîâêà èçìåíåíèé ÑÊÔ è ïðîòåèíóðèè. Ïîñëåäíÿÿ â áîëüøåé ñòåïåíè ñíèæàëàñü ó áîëüíûõ íà ÊÎÒ, íî îäíîâðåìåííî ó ïàöèåíòîâ ýòîé ãðóïïû îòìå÷àëèñü áîëåå áûñòðûå òåìïû ïàäåíèÿ ÑÊÔ.

128
Onuigbo M, Onuigbo N. Late–onset renal failure from angiotensin blockade (LORFFAB) in 100 CKD patients. Int Urol Nephrol 2008; 40: 233–239
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    Îòðèöàòåëüíîå âëèÿíèå íà ôóíêöèþ ïî÷åê ÷ðåçìåðíîãî óãíåòåíèÿ ÐÀÀÑ ïîäòâåðæäàåòñÿ íåäàâíî îïèñàííûì M. Onuigbo è N. Onuigbo LORFFABñèíäðîìîì (Late-Onset Renal Failure from Angiotensin Blockade)
    Exact
    [128]
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    , îñíîâîé äëÿ êîòîðîãî ïîñëóæèë àíàëèç ïðè÷èí ÿòðîãåííîé ïî÷å÷íîé íåäîñòàòî÷íîñòè ó 100 áîëüíûõ. Ó íåêîòîðûõ èç íèõ óäàëîñü èäåíòèôèöèðîâàòü ïðè÷èíó ÎÏÍ (ðåíòãåíîêîíòðàñòíûå èññëåäîâàíèÿ, êàðäèàëüíàÿ õèðóðãèÿ, ïðèåì ÍÏÂÏ), îäíàêî ó áîëüøèíñòâà ïàöèåíòîâ íàðóøåíèå ôóíêöèè ïî÷åê ðàçâèâàëîñü íà ôîíå äëèòåëüíîãî ëå÷åíèÿ ÈÀÏÔ/ÁÐÀ è áûëî, êàê ïðàâèëî, íåîáðàòèìûì.

129
Loriga G, Vidili G, Ruggenenti P et al. Renal hemodynamics and renoprotection. Nephron Clin Pract 2008; 110: 213–219
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    Ó íåêîòîðûõ èç íèõ óäàëîñü èäåíòèôèöèðîâàòü ïðè÷èíó ÎÏÍ (ðåíòãåíîêîíòðàñòíûå èññëåäîâàíèÿ, êàðäèàëüíàÿ õèðóðãèÿ, ïðèåì ÍÏÂÏ), îäíàêî ó áîëüøèíñòâà ïàöèåíòîâ íàðóøåíèå ôóíêöèè ïî÷åê ðàçâèâàëîñü íà ôîíå äëèòåëüíîãî ëå÷åíèÿ ÈÀÏÔ/ÁÐÀ è áûëî, êàê ïðàâèëî, íåîáðàòèìûì.  ýòîé ñâÿçè íåáåçûíòåðåñíû äàííûå î âëèÿíèè áëîêàäû ÐÀÀÑ íà âíóòðèïî÷å÷íóþ ãåìîäèíàìèêó. Ñîãëàñíî G. Loriga è ñîàâò.
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    [129]
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    , â ðåçóëüòàòå 4-íåäåëüíîãî ñî÷åòàííîãî ëå÷åíèÿ áåíàçåïðèëîì (10–20 ìã/ñóò) è âàëñàðòàíîì (80–160 ìã/ñóò) ó áîëüíûõ íåôðîïàòèÿìè çàðåãèñòðèðîâàíî óìåíüøåíèå ïðîòåèíóðèè è çíà÷èìîå ñíèæåíèå ðåçèñòèâíîãî è ïóëüñàòèâíîãî èíäåêñîâ, êîòîðûå â äàëüíåéøåì ñíîâà óâåëè÷èëèñü è ïðîäîëæàëè ïîâûøàòüñÿ â òå÷åíèå ïîñëåäóþùèõ 3 ìåñ.

130
Ogata C, Kamide K, Suzuki Y et al. Evaluation of intrarenal hemodynamics by Doppler ultrasonography for renoprotective effect of angiotensin receptor blockade. Clin Nephrol 2005; 64: 352–357
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    Ñíèæåíèå ïðîòåèíóðèè íå áûëî ñëåäñòâèåì óìåíüøåíèÿ âíóòðèêëóáî÷êîâîé ãèïåðòåíçèè, à àññîöèèðîâàëîñü ñ âîññòàíîâëåíèåì ñåëåêòèâíîñòè ãëîìåðóëÿðíîãî ôèëüòðà.  êðàòêîñðî÷íîì èññëåäîâàíèè C. Ogata è ñîàâò.
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    ñíèæåíèå ðåçèñòèâíîãî èíäåêñà ïîä âëèÿíèåì ÁÐÀ íàáëþäàëîñü ïðåèìóùåñòâåííî ó áîëüíûõ ãèïåðòåíçèâíûì íåôðîàíãèîñêëåðîçîì. Óëó÷øåíèå ýíäîòåëèàëüíîé ôóíêöèè ïîä âëèÿíèåì áëîêàòîðîâ ÐÀÀÑ òàêæå íå ÿâëÿåòñÿ äîëãîâðåìåííûì.

131
Sozen AB, Kayacan MS, Tansel T et al. Drugs with blocking effects on the renin–angiotensin–aldosterone system do not improve endothelial dysfunction long–term in hypertensive patients. J internat Med Res 2009; 37: 996–1002
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    Ogata è ñîàâò. [130] ñíèæåíèå ðåçèñòèâíîãî èíäåêñà ïîä âëèÿíèåì ÁÐÀ íàáëþäàëîñü ïðåèìóùåñòâåííî ó áîëüíûõ ãèïåðòåíçèâíûì íåôðîàíãèîñêëåðîçîì. Óëó÷øåíèå ýíäîòåëèàëüíîé ôóíêöèè ïîä âëèÿíèåì áëîêàòîðîâ ÐÀÀÑ òàêæå íå ÿâëÿåòñÿ äîëãîâðåìåííûì. A. Sozen è ñîàâò.
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    [131]
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    íàçíà÷àëè 44 áîëüíûì ñ íåëå÷åííîé Àà èðáåñàðòàí (300 ìã/ñóò) èëè âàëñàðòàí (160 ìã/ñóò), èëè ôîçèíîïðèë (10 ìã/ ñóò), èëè êâèíîïðèë (20 ìã/ñóò). Ýíäîòåëèàëüíàÿ ôóíêöèÿ (ýíäîòåëèé-çàâèñèìàÿ äèëàòàöèÿ ïëå÷åâîé àðòåðèè) óëó÷øàëàñü óæå ÷åðåç 6 íåä ïîñëå íà÷àëà ëå÷åíèÿ, îäíàêî ÷åðåç 1 ãîä äèàìåòð ïëå÷åâîé àðòåðèè ñòàíîâèëñÿ ìåíüøå èñõîäíîãî.

132
Ahmed A, Kamath N, Kossi M, Nahas A. The impact of stopping inhibitors of the renin-angiotensin system in patients with advanced chronic kidney disease. NDT 2010; 25: 3977– 3982
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    Ýíäîòåëèàëüíàÿ ôóíêöèÿ (ýíäîòåëèé-çàâèñèìàÿ äèëàòàöèÿ ïëå÷åâîé àðòåðèè) óëó÷øàëàñü óæå ÷åðåç 6 íåä ïîñëå íà÷àëà ëå÷åíèÿ, îäíàêî ÷åðåç 1 ãîä äèàìåòð ïëå÷åâîé àðòåðèè ñòàíîâèëñÿ ìåíüøå èñõîäíîãî. Ñîãëàñíî A. Ahmed è ñîàâò.
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    ó ïîæèëûõ áîëüíûõ ñ âûñîêèì ñåðäå÷íî-ñîñóäèñòûì ðèñêîì èìåííî îòìåíà áëîêàòîðîâ ÐÀÀÑ ïîçâîëèëà íå òîëüêî çàìåäëèòü ïðîãðåññèðîâàíèå ÕÏÍ, íî çàìåòíî óëó÷øèòü ôóíêöèþ ïî÷åê [132].  Low Clearance Clinic (LCC) àâòîðû íàáëþäàëè 52 áîëüíûõ â âîçðàñòå 73,3 ãîäà ñ èñõîäíûì óðîâíåì ÑÊÔ (MDRD-ôîðìóëà) 16,38 ìë/ìèí, ó 24 (46%) èç êîòîðûõ ïðè÷èíîé ÕÏÍ ÿâëÿëàñü ÄÍ è òîëüêî ó 5 – ðåíîâàñêóëÿðíàÿ áîëåçíü.

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    Ñîãëàñíî A. Ahmed è ñîàâò. [132] ó ïîæèëûõ áîëüíûõ ñ âûñîêèì ñåðäå÷íî-ñîñóäèñòûì ðèñêîì èìåííî îòìåíà áëîêàòîðîâ ÐÀÀÑ ïîçâîëèëà íå òîëüêî çàìåäëèòü ïðîãðåññèðîâàíèå ÕÏÍ, íî çàìåòíî óëó÷øèòü ôóíêöèþ ïî÷åê
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    [132]
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    .  Low Clearance Clinic (LCC) àâòîðû íàáëþäàëè 52 áîëüíûõ â âîçðàñòå 73,3 ãîäà ñ èñõîäíûì óðîâíåì ÑÊÔ (MDRD-ôîðìóëà) 16,38 ìë/ìèí, ó 24 (46%) èç êîòîðûõ ïðè÷èíîé ÕÏÍ ÿâëÿëàñü ÄÍ è òîëüêî ó 5 – ðåíîâàñêóëÿðíàÿ áîëåçíü.

133
Адашева ТВ, Задионченко ВС, Павлов СВ и др. Органопротективные и плейотропные эффекты амлодипина у больных артериальной гипертензией и обструктивной болезнью легких. Сердце 2010; 9 (3): 165–171
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     ñëó÷àÿõ, êîãäà áëîêàòîðû ÐÀÀÑ ïðîòèâîïîêàçàíû (ñòåíîç ïî÷å÷íîé àðòåðèè) èëè âûçûâàþò ïîáî÷íûå ðåàêöèè (êàøåëü, îòåê Êâèíêå), èëè èõ ïðèìåíåíèå ìàëîýôôåêòèâíî, èëè íåöåëåñîîáðàçíî (ìåäëåííî ïðîãðåññèðóþùèå íåôðîïàòèè ñ ïðîòåèíóðèåé <0,5 ã/ñóò), ìîæíî ñ óñïåõîì ïðèìåíÿòü è äðóãèå ïðåïàðàòû – áëîêàòîðû êàëüöèåâûõ êàíàëîâ
    Exact
    [133–135]
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    , êàëüöèåâûå áëîêàòîðû â ñî÷åòàíèè ñ ÁÐÀ [136], ïåíòîêñèôèëëèí, êîòîðûé ïðè äîáàâëåíèè ê áëîêàòîðàì ÐÀÀÑ ñíèæàë ïðîòåèíóðèþ íà 26% [137]. Óìåíüøåíèå ïðîòåèíóðèè íà 20–40% íàáëþäàåòñÿ ïðè îãðàíè÷åíèè ïîòðåáëåíèÿ áåëêà [138] è îñîáåííî ïðè ñî÷åòàíèè ìàëîáåëêîâîé äèåòû ñ ïðèåìîì ÈÀÏÔ [139].

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Арутюнов ГП, Оганегзова ЛГ. Антагонисты кальциевых каналов и нефропротекция. Сердце: журнал для практикующих врачей 2010; 9 (3): 160–164
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     ñëó÷àÿõ, êîãäà áëîêàòîðû ÐÀÀÑ ïðîòèâîïîêàçàíû (ñòåíîç ïî÷å÷íîé àðòåðèè) èëè âûçûâàþò ïîáî÷íûå ðåàêöèè (êàøåëü, îòåê Êâèíêå), èëè èõ ïðèìåíåíèå ìàëîýôôåêòèâíî, èëè íåöåëåñîîáðàçíî (ìåäëåííî ïðîãðåññèðóþùèå íåôðîïàòèè ñ ïðîòåèíóðèåé <0,5 ã/ñóò), ìîæíî ñ óñïåõîì ïðèìåíÿòü è äðóãèå ïðåïàðàòû – áëîêàòîðû êàëüöèåâûõ êàíàëîâ
    Exact
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    , êàëüöèåâûå áëîêàòîðû â ñî÷åòàíèè ñ ÁÐÀ [136], ïåíòîêñèôèëëèí, êîòîðûé ïðè äîáàâëåíèè ê áëîêàòîðàì ÐÀÀÑ ñíèæàë ïðîòåèíóðèþ íà 26% [137]. Óìåíüøåíèå ïðîòåèíóðèè íà 20–40% íàáëþäàåòñÿ ïðè îãðàíè÷åíèè ïîòðåáëåíèÿ áåëêà [138] è îñîáåííî ïðè ñî÷åòàíèè ìàëîáåëêîâîé äèåòû ñ ïðèåìîì ÈÀÏÔ [139].

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Derwa A, Peeters P, Vanholder R. Calcium Channel blockers in the prevention of end–stage renal disease: a review. Acta clinica belgica 2004; 59 (1): 44–56
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     ñëó÷àÿõ, êîãäà áëîêàòîðû ÐÀÀÑ ïðîòèâîïîêàçàíû (ñòåíîç ïî÷å÷íîé àðòåðèè) èëè âûçûâàþò ïîáî÷íûå ðåàêöèè (êàøåëü, îòåê Êâèíêå), èëè èõ ïðèìåíåíèå ìàëîýôôåêòèâíî, èëè íåöåëåñîîáðàçíî (ìåäëåííî ïðîãðåññèðóþùèå íåôðîïàòèè ñ ïðîòåèíóðèåé <0,5 ã/ñóò), ìîæíî ñ óñïåõîì ïðèìåíÿòü è äðóãèå ïðåïàðàòû – áëîêàòîðû êàëüöèåâûõ êàíàëîâ
    Exact
    [133–135]
    Suffix
    , êàëüöèåâûå áëîêàòîðû â ñî÷åòàíèè ñ ÁÐÀ [136], ïåíòîêñèôèëëèí, êîòîðûé ïðè äîáàâëåíèè ê áëîêàòîðàì ÐÀÀÑ ñíèæàë ïðîòåèíóðèþ íà 26% [137]. Óìåíüøåíèå ïðîòåèíóðèè íà 20–40% íàáëþäàåòñÿ ïðè îãðàíè÷åíèè ïîòðåáëåíèÿ áåëêà [138] è îñîáåííî ïðè ñî÷åòàíèè ìàëîáåëêîâîé äèåòû ñ ïðèåìîì ÈÀÏÔ [139].

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Peng T, Hu Z, Xia Q et al. A comparative study of the renoprotective effects of benidipine and valsartan in primary hypertensive patients with proteinuria. Arzneimittelforschung 2009; 59 (12): 647–650
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     ñëó÷àÿõ, êîãäà áëîêàòîðû ÐÀÀÑ ïðîòèâîïîêàçàíû (ñòåíîç ïî÷å÷íîé àðòåðèè) èëè âûçûâàþò ïîáî÷íûå ðåàêöèè (êàøåëü, îòåê Êâèíêå), èëè èõ ïðèìåíåíèå ìàëîýôôåêòèâíî, èëè íåöåëåñîîáðàçíî (ìåäëåííî ïðîãðåññèðóþùèå íåôðîïàòèè ñ ïðîòåèíóðèåé <0,5 ã/ñóò), ìîæíî ñ óñïåõîì ïðèìåíÿòü è äðóãèå ïðåïàðàòû – áëîêàòîðû êàëüöèåâûõ êàíàëîâ [133–135], êàëüöèåâûå áëîêàòîðû â ñî÷åòàíèè ñ ÁÐÀ
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    , ïåíòîêñèôèëëèí, êîòîðûé ïðè äîáàâëåíèè ê áëîêàòîðàì ÐÀÀÑ ñíèæàë ïðîòåèíóðèþ íà 26% [137]. Óìåíüøåíèå ïðîòåèíóðèè íà 20–40% íàáëþäàåòñÿ ïðè îãðàíè÷åíèè ïîòðåáëåíèÿ áåëêà [138] è îñîáåííî ïðè ñî÷åòàíèè ìàëîáåëêîâîé äèåòû ñ ïðèåìîì ÈÀÏÔ [139].

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Renke M, Tylicki L, Rutkowski P et al. Effect of pentoxifylline on proteinuria, markers of tubular injury and oxidative stress in non–diabetic patients with chronic kidney disease – placebo controlled, randomized, cross–over study. Acta Biochim Pol 2010; 57 (1): 119–123
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    àðòåðèè) èëè âûçûâàþò ïîáî÷íûå ðåàêöèè (êàøåëü, îòåê Êâèíêå), èëè èõ ïðèìåíåíèå ìàëîýôôåêòèâíî, èëè íåöåëåñîîáðàçíî (ìåäëåííî ïðîãðåññèðóþùèå íåôðîïàòèè ñ ïðîòåèíóðèåé <0,5 ã/ñóò), ìîæíî ñ óñïåõîì ïðèìåíÿòü è äðóãèå ïðåïàðàòû – áëîêàòîðû êàëüöèåâûõ êàíàëîâ [133–135], êàëüöèåâûå áëîêàòîðû â ñî÷åòàíèè ñ ÁÐÀ [136], ïåíòîêñèôèëëèí, êîòîðûé ïðè äîáàâëåíèè ê áëîêàòîðàì ÐÀÀÑ ñíèæàë ïðîòåèíóðèþ íà 26%
    Exact
    [137]
    Suffix
    . Óìåíüøåíèå ïðîòåèíóðèè íà 20–40% íàáëþäàåòñÿ ïðè îãðàíè÷åíèè ïîòðåáëåíèÿ áåëêà [138] è îñîáåííî ïðè ñî÷åòàíèè ìàëîáåëêîâîé äèåòû ñ ïðèåìîì ÈÀÏÔ [139]. Ñíèæåíèå ýêñêðåöèè àëüáóìèíà ñ ìî÷îé íàáëþäàåòñÿ ó áîëüíûõ ÄÍ ñ ÌÀÓ è ïðîòåèíóðèåé íà ôîíå ëå÷åíèÿ òèàçîëèäèíåäèîíàìè [140].

138
Kaysen GA, Gambertoglio J, Jimenez I et al. Effect of dietary protein intake on albumin homeostasis in nephrotic patients. Kidney Int 1986; 29: 572–577
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    , èëè íåöåëåñîîáðàçíî (ìåäëåííî ïðîãðåññèðóþùèå íåôðîïàòèè ñ ïðîòåèíóðèåé <0,5 ã/ñóò), ìîæíî ñ óñïåõîì ïðèìåíÿòü è äðóãèå ïðåïàðàòû – áëîêàòîðû êàëüöèåâûõ êàíàëîâ [133–135], êàëüöèåâûå áëîêàòîðû â ñî÷åòàíèè ñ ÁÐÀ [136], ïåíòîêñèôèëëèí, êîòîðûé ïðè äîáàâëåíèè ê áëîêàòîðàì ÐÀÀÑ ñíèæàë ïðîòåèíóðèþ íà 26% [137]. Óìåíüøåíèå ïðîòåèíóðèè íà 20–40% íàáëþäàåòñÿ ïðè îãðàíè÷åíèè ïîòðåáëåíèÿ áåëêà
    Exact
    [138]
    Suffix
    è îñîáåííî ïðè ñî÷åòàíèè ìàëîáåëêîâîé äèåòû ñ ïðèåìîì ÈÀÏÔ [139]. Ñíèæåíèå ýêñêðåöèè àëüáóìèíà ñ ìî÷îé íàáëþäàåòñÿ ó áîëüíûõ ÄÍ ñ ÌÀÓ è ïðîòåèíóðèåé íà ôîíå ëå÷åíèÿ òèàçîëèäèíåäèîíàìè [140]. Âîññòàíîâèòü ÷óâñòâèòåëüíîñòü ê áëîêàòîðàì ÐÀÀÑ âîçìîæíî áîëåå ñòðîãèì îãðàíè÷åíèåì ïîòðåáëåíèÿ ñîëè èëè äîáàâëåíèåì íàòðèéóðåòèêîâ.

139
Gansevoort RT, de Zeeuw D, de Jong PR. Additive antiproteinuric effect of ACE inhibition and a low–protein diet in human renal disease. Nephrol Dial Transplant 1995; 10: 497– 504
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    ñ ïðîòåèíóðèåé <0,5 ã/ñóò), ìîæíî ñ óñïåõîì ïðèìåíÿòü è äðóãèå ïðåïàðàòû – áëîêàòîðû êàëüöèåâûõ êàíàëîâ [133–135], êàëüöèåâûå áëîêàòîðû â ñî÷åòàíèè ñ ÁÐÀ [136], ïåíòîêñèôèëëèí, êîòîðûé ïðè äîáàâëåíèè ê áëîêàòîðàì ÐÀÀÑ ñíèæàë ïðîòåèíóðèþ íà 26% [137]. Óìåíüøåíèå ïðîòåèíóðèè íà 20–40% íàáëþäàåòñÿ ïðè îãðàíè÷åíèè ïîòðåáëåíèÿ áåëêà [138] è îñîáåííî ïðè ñî÷åòàíèè ìàëîáåëêîâîé äèåòû ñ ïðèåìîì ÈÀÏÔ
    Exact
    [139]
    Suffix
    . Ñíèæåíèå ýêñêðåöèè àëüáóìèíà ñ ìî÷îé íàáëþäàåòñÿ ó áîëüíûõ ÄÍ ñ ÌÀÓ è ïðîòåèíóðèåé íà ôîíå ëå÷åíèÿ òèàçîëèäèíåäèîíàìè [140]. Âîññòàíîâèòü ÷óâñòâèòåëüíîñòü ê áëîêàòîðàì ÐÀÀÑ âîçìîæíî áîëåå ñòðîãèì îãðàíè÷åíèåì ïîòðåáëåíèÿ ñîëè èëè äîáàâëåíèåì íàòðèéóðåòèêîâ.

140
Sarafidis PA, Stafylas PC, Georgianos PI et al. Effect of Thiazolidinediones on Albuminuria and Proteinuria in Diabetes: A Meta–analysis. Am J Kidney Dis 2010; 55: 853–847
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  1. In-text reference with the coordinate start=39720
    Prefix
    Óìåíüøåíèå ïðîòåèíóðèè íà 20–40% íàáëþäàåòñÿ ïðè îãðàíè÷åíèè ïîòðåáëåíèÿ áåëêà [138] è îñîáåííî ïðè ñî÷åòàíèè ìàëîáåëêîâîé äèåòû ñ ïðèåìîì ÈÀÏÔ [139]. Ñíèæåíèå ýêñêðåöèè àëüáóìèíà ñ ìî÷îé íàáëþäàåòñÿ ó áîëüíûõ ÄÍ ñ ÌÀÓ è ïðîòåèíóðèåé íà ôîíå ëå÷åíèÿ òèàçîëèäèíåäèîíàìè
    Exact
    [140]
    Suffix
    . Âîññòàíîâèòü ÷óâñòâèòåëüíîñòü ê áëîêàòîðàì ÐÀÀÑ âîçìîæíî áîëåå ñòðîãèì îãðàíè÷åíèåì ïîòðåáëåíèÿ ñîëè èëè äîáàâëåíèåì íàòðèéóðåòèêîâ. Äëÿ ïðåîäîëåíèÿ ðåôðàêòåðíîñòè ê ïðåïàðàòàì íà ôîíå ãèïåðñèìïàòèêîòîíèè öåëåñîîáðàçíî ïðèñîåäèíåíèå ñèìïàòîëèòèêîâ (ìîêñîíèäèíà, β1-áëîêàòîðîâ, êàðâåäèîëà) [141], ðåêîìåíäóåòñÿ îòêàç îò êóðåíèÿ [142].

141
Blankestijn PJ. Sympathetic hyperactivity in chronic kidney disease. NDT 2004; 19 (6): 1354–1357
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    Âîññòàíîâèòü ÷óâñòâèòåëüíîñòü ê áëîêàòîðàì ÐÀÀÑ âîçìîæíî áîëåå ñòðîãèì îãðàíè÷åíèåì ïîòðåáëåíèÿ ñîëè èëè äîáàâëåíèåì íàòðèéóðåòèêîâ. Äëÿ ïðåîäîëåíèÿ ðåôðàêòåðíîñòè ê ïðåïàðàòàì íà ôîíå ãèïåðñèìïàòèêîòîíèè öåëåñîîáðàçíî ïðèñîåäèíåíèå ñèìïàòîëèòèêîâ (ìîêñîíèäèíà, β1-áëîêàòîðîâ, êàðâåäèîëà)
    Exact
    [141]
    Suffix
    , ðåêîìåíäóåòñÿ îòêàç îò êóðåíèÿ [142]. Ðåöåïòîðû ê ðåíèíó (ïðîðåíèíó) îáíàðóæåíû íà ìåçàíãèàëüíûõ è ãëàäêîìûøå÷íûõ êëåòêàõ ïî÷å÷íûõ ñîñóäîâ [143]. Âçàèìîäåéñòâèå ðåíèíà ñ ýòèìè ðåöåïòîðàìè èíäóöèðóåò ýêñïðåññèþ íà ìåçàíãèàëüíûõ êëåòêàõ ÒÔÐ-β1 è âëèÿåò íà òîíóñ ñîñóäîâ àíãèîòåíçèí-íåçàâèñèìûì ìåõàíèçìîì.

142
Orth SR, Schroeder T., Ritz E. Effects of smoking on renal function in patients with type 1 and type 2 diabetes mellitus. NDT 2005; 20: 2414–2419
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    Âîññòàíîâèòü ÷óâñòâèòåëüíîñòü ê áëîêàòîðàì ÐÀÀÑ âîçìîæíî áîëåå ñòðîãèì îãðàíè÷åíèåì ïîòðåáëåíèÿ ñîëè èëè äîáàâëåíèåì íàòðèéóðåòèêîâ. Äëÿ ïðåîäîëåíèÿ ðåôðàêòåðíîñòè ê ïðåïàðàòàì íà ôîíå ãèïåðñèìïàòèêîòîíèè öåëåñîîáðàçíî ïðèñîåäèíåíèå ñèìïàòîëèòèêîâ (ìîêñîíèäèíà, β1-áëîêàòîðîâ, êàðâåäèîëà) [141], ðåêîìåíäóåòñÿ îòêàç îò êóðåíèÿ
    Exact
    [142]
    Suffix
    . Ðåöåïòîðû ê ðåíèíó (ïðîðåíèíó) îáíàðóæåíû íà ìåçàíãèàëüíûõ è ãëàäêîìûøå÷íûõ êëåòêàõ ïî÷å÷íûõ ñîñóäîâ [143]. Âçàèìîäåéñòâèå ðåíèíà ñ ýòèìè ðåöåïòîðàìè èíäóöèðóåò ýêñïðåññèþ íà ìåçàíãèàëüíûõ êëåòêàõ ÒÔÐ-β1 è âëèÿåò íà òîíóñ ñîñóäîâ àíãèîòåíçèí-íåçàâèñèìûì ìåõàíèçìîì.

143
Huang Y, Wongamorntham S, Kasting J et al. Renin increases mesangial cell transforming growth factor–в1 and matrix proteins through receptor–mediated, angiotensin II– independent mechanisms. Kidney Int 2006; 69: 13–15
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    Äëÿ ïðåîäîëåíèÿ ðåôðàêòåðíîñòè ê ïðåïàðàòàì íà ôîíå ãèïåðñèìïàòèêîòîíèè öåëåñîîáðàçíî ïðèñîåäèíåíèå ñèìïàòîëèòèêîâ (ìîêñîíèäèíà, β1-áëîêàòîðîâ, êàðâåäèîëà) [141], ðåêîìåíäóåòñÿ îòêàç îò êóðåíèÿ [142]. Ðåöåïòîðû ê ðåíèíó (ïðîðåíèíó) îáíàðóæåíû íà ìåçàíãèàëüíûõ è ãëàäêîìûøå÷íûõ êëåòêàõ ïî÷å÷íûõ ñîñóäîâ
    Exact
    [143]
    Suffix
    . Âçàèìîäåéñòâèå ðåíèíà ñ ýòèìè ðåöåïòîðàìè èíäóöèðóåò ýêñïðåññèþ íà ìåçàíãèàëüíûõ êëåòêàõ ÒÔÐ-β1 è âëèÿåò íà òîíóñ ñîñóäîâ àíãèîòåíçèí-íåçàâèñèìûì ìåõàíèçìîì.  ñèëó ýòîãî ñî÷åòàíèå áëîêàòîðîâ ÐÀÀÑ ñ ïðÿìûì èíãèáèòîðîì ñåêðåöèè ðåíèíà àëèñêèðåíîì ÿâëÿåòñÿ ïåðñïåêòèâíûì íàïðàâëåíèåì â ëå÷åíèè íå òîëüêî ÀÃ, íî è íåôðîïàòèé, ïðîòåêàþùèõ ñ ìàññèâíîé ïðîòåèíóðèåé [144, 145].

144
Kushiro T, Itakura H, Abo Y et al. Aliskiren, a novel oral renin inhibitor provides dose–dependent efficacy and placebo– like tolerability in Japanese patients with hypertension. Hypertens Res 2006; 29: 997–1005
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    Prefix
     ñèëó ýòîãî ñî÷åòàíèå áëîêàòîðîâ ÐÀÀÑ ñ ïðÿìûì èíãèáèòîðîì ñåêðåöèè ðåíèíà àëèñêèðåíîì ÿâëÿåòñÿ ïåðñïåêòèâíûì íàïðàâëåíèåì â ëå÷åíèè íå òîëüêî ÀÃ, íî è íåôðîïàòèé, ïðîòåêàþùèõ ñ ìàññèâíîé ïðîòåèíóðèåé
    Exact
    [144, 145]
    Suffix
    . Çàêëþ÷åíèå Àíàëèç ïðèâåäåííûõ äàííûõ ñâèäåòåëüñòâóåò, ÷òî ÐÀÀÑ èãðàåò âàæíóþ ðîëü â ïðîãðåññèðîâàíèè íåôðîïàòèé ðàçëè÷íîãî ãåíåçà, àãðàâèðóÿ àðòåðèàëüíóþ ãèïåðòåíçèþ è ïðîòåèíóðèþ, à áëîêàòîðû ÐÀÀÑ ñ ìîìåíòà âíåäðåíèÿ â øèðîêóþ êëèíè÷åñêóþ ïðàêòèêó, áëàãîäàðÿ àíòèãèïåðòåíçèâíîìó è àíòèïðîòåèíóðè÷åñêîìó ýôôåêòàì, ñ÷èòàþòñÿ èñòèííûìè íåôðîïðîòåêòîðàìè, çàìåäëÿþùèìè ïðîãðåññèðîâàíèå äèàáåòè÷åñêîé í

145
Parving HH, Persson F, Lewis JB, Hollenberg NK. AVOID Study Investigators. Aliskiren combined with losartan in type 2 diabetes and nephropathy. N Engl J Med 2008; 358: 2433–2446 Ïîñòóïèëà â ðåäàêöèþ 14.04.2011 ã.
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  1. In-text reference with the coordinate start=40522
    Prefix
     ñèëó ýòîãî ñî÷åòàíèå áëîêàòîðîâ ÐÀÀÑ ñ ïðÿìûì èíãèáèòîðîì ñåêðåöèè ðåíèíà àëèñêèðåíîì ÿâëÿåòñÿ ïåðñïåêòèâíûì íàïðàâëåíèåì â ëå÷åíèè íå òîëüêî ÀÃ, íî è íåôðîïàòèé, ïðîòåêàþùèõ ñ ìàññèâíîé ïðîòåèíóðèåé
    Exact
    [144, 145]
    Suffix
    . Çàêëþ÷åíèå Àíàëèç ïðèâåäåííûõ äàííûõ ñâèäåòåëüñòâóåò, ÷òî ÐÀÀÑ èãðàåò âàæíóþ ðîëü â ïðîãðåññèðîâàíèè íåôðîïàòèé ðàçëè÷íîãî ãåíåçà, àãðàâèðóÿ àðòåðèàëüíóþ ãèïåðòåíçèþ è ïðîòåèíóðèþ, à áëîêàòîðû ÐÀÀÑ ñ ìîìåíòà âíåäðåíèÿ â øèðîêóþ êëèíè÷åñêóþ ïðàêòèêó, áëàãîäàðÿ àíòèãèïåðòåíçèâíîìó è àíòèïðîòåèíóðè÷åñêîìó ýôôåêòàì, ñ÷èòàþòñÿ èñòèííûìè íåôðîïðîòåêòîðàìè, çàìåäëÿþùèìè ïðîãðåññèðîâàíèå äèàáåòè÷åñêîé í