안지오텐신 2의 사구체 상피세포 ZO-1에 대한 영향

구현회 ( Hyun Hoe Koo ),하태선 ( Tae Sun Ha ) 대한신장학회 2007 Kidney Research and Clinical Practice Vol.26 No.5

Purpose : Angiotensin II plays a potent role in renal injury not only by vasoconstrictive effects but also by biochemical effects. We investigated the effect of angiotensin II on ZO-1 (zonular occludens-1), a component of the slit diaphragm domain connecting slit diaphragm structure and actin cytoskeleton, in the glomerular epithelial cells (podocytes) for the glomerular damage. We tried to find that this effect could be prevented by losartan, an angiotensin II type 1 receptor blocker. Methods : Glomerular epithelial cells were treated with various concentrations of angiotensin II and losartan. The distribution of ZO-1 was observed by confocal microscope and the change of ZO-1 expression was measured by Western blotting and RT-PCR. Results : The intensities of fluorescences and bands of ZO-1 protein were decreased by angiotensin II in a dose-dependent manner by confocal microscopy and Western blot analysis, respectively. ZO-1 also moved from peripheral to inner cytoplasm and lost its linear pattern. These distributional changes of ZO-1 protein by angiotensin II were reversed by losartan in a dose-dependent manner. Angiotensin II reduced the amount and mRNA expresssion of ZO-1 which were also reversed by losartan. Conclusion : Angiotensin II decreases the amount of ZO-1 protein and changes its localization through angiotensin II type 1 receptor. These findings suggest that angiotensin II-added condition induces the cytoplasmic translocation and suppresses the production of ZO-1 in podocytes at transcriptional level, and could be prevented by angiotensin receptor antagonists.

만성 신장병 환자에서 레닌-안지오텐신계 억제제와 칼륨교환수지 동시 사용이 혈청 칼륨에 미치는 영향

이주학 ( Joo Hark Yi ),윤여욱 ( Yeo Wook Yun ),노유석 ( U Seok Noh ),김은영 ( Eun Young Kim ),박재일 ( Jae Il Park ),한상웅 ( Sang Woong Han ),김호중 ( Ho Jung Kim ) 대한신장학회 2007 Kidney Research and Clinical Practice Vol.26 No.5

Purpose : This prospective study aimed to evaluate the safety and efficacy of potassium-exchange resin (PER, Kalimateⓡ or Argamateⓡ) for managing hyperkalemia induced by Renin-Angiotensin System (RAS) blockers in chronic kidney disease (CKD) patients without their discontinuation. Methods : Besides conservative remedies including low-potassium diet, all hyperkalemic CKD patients (n=21, [K] ≥5.6 mEq/L) received PER added on angiotensin-converting enzyme inhibitor (Moexipril, n=2) or angiotensin-receptor blocker (Irbesartan, n=19) with, at least, weekly monitoring of serum [K] if its level remains more than 5.5 mEq/L for more than 2 months (mean±SD, 6.8±5.9 mon; range, 2-26 mon). Results : Baseline serum [K] on RAS blocker alone (5.1±0.4 mEq/L; 4.2-6.3 mEq/L) increased to 6.0 ±0.4 mEq/L (p<0.05) before adding PER, and then it was significantly decreased to 5.3±0.6 mEq/L at the first clinic visit (p<0.05) and to 5.0±0.7 mEq/L at the last clinic visit (p<0.05) following the administration of PER added on RAS blocker. During the study period, GFR, serum creatinine and urinary protein excretion didn`t change significantly. Conclusion : The development of hyperkalemia on RAS blockers in CKD patients doesn`t necessarily lead to withdrawal of RAS blockers when the cautious add-on therapy of potassium-exchange resin with other conservative remedies launches, unless severe refractory hyperkalemia persists. II type 1 receptor blockers

Comparison of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in patients with diabetes mellitus and non-ST-segment elevation myocardial infarction who underwent successful percutaneous coronary intervention

Byun, Jae Kyeong,Choi, Byoung Geol,Rha, Seung-Woon,Choi, Se Yeon,Jeong, Myung Ho Elsevier 2018 Atherosclerosis Vol.277 No.-

<P><B>Abstract</B></P> <P><B>Background and aims</B></P> <P>Angiotensin-converting-enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) are known to be beneficial for either non-ST-segment elevation myocardial infarction (NSTEMI) patients or diabetes mellitus (DM) patients. However, the comparative efficacy of ACEI <I>versus</I> ARB in patients with NSTEMI and DM is unclear. The aim of this study was to compare the protective efficacy of ACEI <I>versus</I> ARB in patients with NSTEMI and DM, who underwent percutaneous coronary intervention (PCI) with drug-eluting stents (DES).</P> <P><B>Methods</B></P> <P>Among 53,281 patients enrolled in the nationwide Korea Acute Myocardial Infarction Registry, 3426 patients with NSTEMI and DM, who were treated with renin-angiotensin system (RAS) inhibitors, had undergone successful PCI with DESs. They were classified into two groups: ACEI group (<I>N</I> = 2076), and ARB group (<I>N</I> = 1350). Individual major clinical outcomes and major adverse cardiac events (MACE), the composite of total death, myocardial infarction (MI), and revascularization were compared between the two groups for up to two years.</P> <P><B>Results</B></P> <P>After propensity score-matching analysis, two propensity-matched groups (1103 pairs, total = 2206) were generated, and the baseline characteristics were balanced. Although all causes of death and recurrent MI were not different between the two groups, the incidence of revascularization (4.0% <I>vs.</I> 7.1%; <I>p</I> = 0.002), including target vessel (2.3% <I>vs.</I> 5.0; <I>p</I> = 0.002), and MACE (8.7% <I>vs.</I> 12.5%, <I>p</I> = 0.008), were lower in the ACEI group than the ARB group at two-year follow-up.</P> <P><B>Conclusions</B></P> <P>Compared with ARB, no beneficial effects of ACEI on all causes of death, cardiac death, or recurrence of MI were observed, but ACEI reduced the incidence of revascularization and MACE in this population. Thus, well-designed trials with a larger population are needed to confirm these results.</P> <P><B>Highlights</B></P> <P> <UL> <LI> No beneficial effects of ACEI on total deaths, cardiac deaths, or recurrence of MI were observed. </LI> <LI> ACEI reduced the incidence of revascularization and MACE. </LI> <LI> In subgroup analysis, ACEI had a beneficial effect on MACE. </LI> </UL> </P>

안지오텐신 변환효소 억제제와 안지오텐신 II 수용체 차단제 투여 후 발생한 급성 신부전과 폐부종으로 전원된 선천성 단일신 환자의 치료 1예

백두현,김경진,홍성철,강석형,송하응,김혜인,김수현,오현정,강혜원,김서우,유민아,류동열,최규복,강덕희 이화여자대학교 의과대학 2010 EMJ (Ewha medical journal) Vol.33 No.1

Blockers of renin-angiotensin system(RAS) including ACE inhibitor or ARB are one of the most frequently prescribed medications for the treatment of hypertension, heart failure and proteinuria. One of the major side effects of these RAS blockers is the deterioration of renal function, mainly due to a reduction of intraglomerular pressure. Therefore, close monitoring of renal function is recommended when RAS blockers are initially prescribed, especially for the patients with impaired renal function. We report a patient who was transferred to our hospital due to the sudden development of oliguria and dyspnea after treatment for hypertension with ACEi and ARB. She was finally diagnosed as RAS blocker-induced acute renal failure with pulmonary edema complicated on congenital solitary kidney. After hemodialysis and conservative treatment, her renal function was recovered with maintenance of normal urine output. Conclusion:This case highlights the necessity of the functional and structural evaluation of kidney to prevent the serious complication such as acute renal failure before the administration of ACEi and/or ARB.

Angiotensin Receptor Blockers as an Alternative to Angiotensin-Converting Enzyme Inhibitors in Patients with Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention

임성민,추은호,최익준,임상현,김희열,안영근,장기육,정명호,승기배 대한의학회 2019 Journal of Korean medical science Vol.34 No.45

Background: Angiotensin-converting enzyme inhibitors (ACEIs) are the first choice for the treatment of acute myocardial infarction (AMI), and angiotensin receptor blockers (ARBs) should be considered in patients intolerant to ACEIs. Although previous studies support the use of ARBs as an alternative to ACEIs, these studies showed inconsistent results. The objective of this study was to demonstrate the clinical impact of ARBs as an alternative to ACEIs in patients with AMI undergoing percutaneous coronary intervention (PCI). Methods: The CardiOvascular Risk and idEntificAtion of potential high-risk population in AMI (COREA-AMI) registry enrolled all consecutive patients with AMI undergoing PCI. The primary endpoint was the composite of cardiovascular death, myocardial infarction, stroke, or hospitalization due to heart failure. Results: Of the 3,328 eligible patients, ARBs replaced ACEIs in 816 patients, while 824 patients continued to use ACEIs and 826 patients continued to use ARBs. The remaining 862 patients did not receive ACEIs/ARBs. After the adjustment with inverse probability weighting, the primary endpoints in the first groups were similar (7.5% vs. 8.0%, hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.75–1.05; P = 0.164). Composite events were less frequent in the ACEI to ARB group than no ACEI/ARB group (7.5% vs. 11.8%, HR, 0.76; 95% CI, 0.64–0.90; P = 0.002). Conclusion: The alternative use of ARBs following initial treatment with ACEIs demonstrates comparable clinical outcomes to those with continued use of ACEIs and is associated with an improved rate of composite events compared to no ACEI/ARB use in patients with AMI undergoing PCI.

Angiotensin-converting enzyme inhibitors versus angiotensin II receptor blockers in acute ST-segment elevation myocardial infarction patients with diabetes mellitus undergoing percutaneous coronary intervention

Choi, Se Yeon,Choi, Byoung Geol,Rha, Seung-Woon,Byun, Jae Kyeong,Shim, Min suk,Li, Hu,Mashaly, Ahmed,Choi, Cheol Ung,Park, Chang Gyu,Seo, Hong Seog,Oh, Dong Joo,Jeong, Myung Ho Elsevier 2017 INTERNATIONAL JOURNAL OF CARDIOLOGY Vol.249 No.-

<P><B>Abstract</B></P> <P><B>Background</B></P> <P>Diabetes Mellitus (DM) is an important factor of adverse cardiovascular events in acute ST-segment elevation myocardial infarction (STEMI) patients. Renin-angiotensin-aldosterone system (RAAS) inhibitors is associated with improved clinical outcomes, however, there are limited data comparing the effectiveness of two different RAAS inhibitors in STEMI patients with DM undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES).</P> <P><B>Methods</B></P> <P>A total of 3811 eligible STEMI patients with DM were enrolled in Korea Acute Myocardial Infarction Registry (KAMIR). They were stratified into two groups: Angiotensin converting enzyme inhibitors (ACEI) group (n=2691) and angiotensin receptor blockers (ARB) group (n=1120). To adjust baseline confounding factors, we performed propensity score matching (PSM) analysis and evaluated individual and composite major clinical outcomes between the two groups up to 2years.</P> <P><B>Results</B></P> <P>After PSM, a total of 1049 well-matched pairs were generated. Baseline clinical, angiographic and procedural characteristics were well-balanced between the two groups. The incidence of death, recurrent myocardial infarction (MI), revascularization and major adverse cardiac events (MACE) were not significantly different between the two groups up to 2years,</P> <P><B>Conclusion</B></P> <P>In the present study, ACEI and ARB showed comparable effectiveness and safety on individual and composite clinical outcomes in STEMI patients with DM who underwent successful PCI with DES at least up to 2years.</P>

Case Report : Severe Hyponatremia Associated with the Use of Angiotensin II Receptor Blocker/thiazide Combinations

( Da Rae Kim ),( Joo Hee Cho ),( Won Seok Jang ),( Jin Sug Kim ),( Kyung Hwan Jeong ),( Tae Won Lee ),( Chun Gyoo Ihm ) 대한전해질학회 2013 Electrolytes & Blood Pressure Vol.11 No.2

There are several widely used combinations of angiotensin II receptor blocker (ARB)/ thiazide. The complimentary mechanism of action for such antihypertensive therapies is that, while ARB inhibits the vasoconstricting and aldosterone-secreting effects of angiotensin II, hydrochlorothiazide affects the renal tubular mechanisms of electrolyte reabsorption and increases excretion of sodium and chloride in the distal tubule, consequently promoting water excretion. In addition, hypokalemia, which may be triggered by a hydrochlorothiazide-induced increase in urinary potassium loss, is resisted by the use of ARB. Hence, the ARB/thiazide combination is safe in terms of potassium imbalance. For these reasons, fixed-dose ARB/thiazide combination anti-hypertensive drugs have been widely used for the treatment of hypertension. However, there have not been many studies done regarding cases where patients under such regimens showed severe hyponatremia,even when the amount of thiazide included was low. Here we report two cases in which severe hyponatremia occurred following treatment with the ARB/thiazide combinations. Upon discontinuation of the regimen, both patients showed recovery from hyponatremia.

Possible Liver Injury in Patients Treated with Fimasartan, a Novel Angiotensin II Receptor Blocker: Experience of a Single Tertiary Health Care Center

( Jae-jun Shim ),( Jae Hoon Park ),( Jong Sin Woo ),( Byung-ho Kim ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: We recently experienced two cases with severe hepatotoxicity associated with fimasartan, a novel angiotensin II receptor blocker (ARB) in Korea. We investigated incidence of significant liver injury (SLI) among patients receiving various ARBs in a tertiary health care center. Methods: SLI was defined as increased serum level of alanine aminotransferase (ALT) more than 3-fold of upper limit of normal (male > 90 U/L, female > 57 U/L). The patients who started ARB and had available baseline and follow-up ALT levels were enrolled during 2011 to 2016. Another class of antihypertensive agent, amlodipine was investigated as a control group. Results: A total of 13,122 patients were enrolled. Mean age was 61.3 years and female to male ratio was 50.5:49.5. Mean baseline ALT level was 24.6 U/L. Following ARB treatment, change of ALT level was only found in fimasartan group (24.7 to 34.8 U/L, P<0.001 by paired t-test). The incidence of SLI was 5.4%, 2.1%, 2.1%, and 2.5% in fimasartan (N = 930), candensartan (N = 5,941), valsartan (N = 2,980), and amlodipine group (N = 3,271), respectively (P<0.001). Even after propensity score matching, the incidence of SLI in fimasartan group was significantly higher than the other groups (P< 0.05). In a multivariate Cox proportional hazard model, SLI was independently associated with higher baseline ALT level, female, younger age, and fimasartan use. Severe liver damage (ALT > 200 U/L) was found in 45 patients and most of them were not related to medication. Only 4 patients were clinically related to antihypertensive agent, exclusively fimasartan. Causality assessment grades in those patients were all probable (score: 6-8). Conclusions: Fimasartan might be associated with hepatotoxicity in a small group of patients. A large scale survey to characterize its clinical outcomes and to find high-risk group is needed.

Angiotensin II type 1 receptor blockers as a first choice in patients with acute myocardial infarction

( Jang Hoon Lee ),( Myung Hwan Bae ),( Dong Heon Yang ),( Hun Sik Park ),( Yongkeun Cho ),( Won Kee Lee ),( Myung Ho Jeong ),( Young Jo Kim ),( Myeong Chan Cho ),( Chong Jin Kim ),( Shung Chull Chae ) 대한내과학회 2016 The Korean Journal of Internal Medicine Vol.31 No.2

Background/Aims: Angiotensin II type 1 receptor blockers (ARBs) have not been adequately evaluated in patients without left ventricular (LV) dysfunction or heart failure after acute myocardial infarction (AMI). Methods: Between November 2005 and January 2008, 6,781 patients who were not receiving angiotensin-converting enzyme inhibitors (ACEIs) or ARBs were selected from the Korean AMI Registry. The primary endpoints were 12-month major adverse cardiac events (MACEs) including death and recurrent AMI. Results: Seventy percent of the patients were Killip class 1 and had a LV ejection fraction 40%. The prescription rate of ARBs was 12.2%. For each patient, a propensity score, indicating the likelihood of using ARBs during hospitalization or at discharge, was calculated using a non-parsimonious multivariable logistic regression model, and was used to match the patients 1:4, yielding 715 ARB users versus 2,860 ACEI users. The effect of ARBs on in-hospital mortality and 12-month MACE occurrence was assessed using matched logistic and Cox regression models. Compared with ACEIs, ARBs significantly reduced in-hospital mortality (1.3% vs. 3.3%; hazard ratio [HR], 0.379; 95% confidence interval [CI], 0.190 to 0.756; p = 0.006) and 12-month MACE occurrence (4.6% vs. 6.9%; HR, 0.661; 95% CI, 0.457 to 0.956; p = 0.028). However, the benefit of ARBs on 12-month mortality compared with ACEIs was marginal (4.3% vs. 6.2%; HR, 0.684; 95% CI, 0.467 to 1.002; p = 0.051). Conclusions: Our results suggest that ARBs are not inferior to, and may actually be better than ACEIs in Korean patients with AMI.

Clinical outcomes of COVID-19 following the use of angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers among patients with hypertension in Korea: a nationwide study

Ju Hwan Kim,Yeon-Hee Baek,Hyesung Lee,Young June Choe,Hyun Joon Shin,Ju-Young Shin 한국역학회 2021 Epidemiology and Health Vol.43 No.-

OBJECTIVES: Recent evidence has shown no harm associated with the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin-receptor blockers (ARBs) in patients with coronavirus disease 2019 (COVID-19). We sought to further clarify the possible association between ACEI/ARB use and the risk of poor clinical outcomes of COVID-19. METHODS: From the completely enumerated COVID-19 cohort in Korea, we identified 1,290 patients with hypertension, of whom 682 had and 603 did not have records of ACEI/ARB use during the 30-day period before their COVID-19 diagnosis. Our primary endpoint comprised clinical outcomes, including all-cause mortality, use of mechanical ventilation, intensive care unit admission, and sepsis. We used inverse probability of treatment weighting (IPTW) to mitigate selection bias, and a Poisson regression model to estimate the relative risks (RRs) and 95% confidence intervals (CIs) for comparing outcomes between ACEI/ARB users and non-users. RESULTS: Compared to non-use, ACEI/ARB use was associated with lower clinical outcomes (IPTW-adjusted RR, 0.60; 95% CI, 0.42 to 0.85; p=0.005). For individual outcomes, ACEI/ARB use was not associated with all-cause mortality (IPTW-adjusted RR, 0.62; 95% CI, 0.35 to 1.09; p=0.097) or respiratory events (IPTW-adjusted RR, 0.99; 95% CI, 0.84 to 1.17; p=0.904). Subgroup analysis showed a trend toward a protective role of ACEIs and ARBs against overall outcomes in men (IPTW-adjusted RR, 0.84; 95% CI, 0.69 to 1.03; pinteraction=0.008) and patients with pre-existing respiratory disease (IPTW-adjusted RR, 0.74; 95% CI, 0.60 to 0.92; pinteraction=0.002). CONCLUSIONS: We present clinical evidence to support continuing ACE/ARB use in COVID-19 patients with hypertension based on the completely enumerated Korean cohort.