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1 梨花醫大誌 : 第 33 卷第 1 號 2010 Ewha Med J Vol. 33, No. 1, 2010 online ML Comm 안지오텐신변환효소억제제와안지오텐신 II 수용체 차단제투여후발생한급성신부전과폐부종으로전원된 선천성단일신환자의치료 1 예 = Abstract = 이화여자대학교의학전문대학원내과학교실 백두현 김경진 홍성철 강석형 송하응 김혜인 김수현오현정 강혜원 김서우 유민아 류동열 최규복 강덕희 Acute Renal Failure with Pulmonary Edema Induced by the Treatment of Angiotensin-Converting Enzyme Inhibitor and Angiotensin II Receptor Blocker in a Patient with Congenital Solitary Kidney Doo Hyun Baek Kyung Jin Kim Sung Chul Hong Suk Hyung Kang Ha Eung Song Hye In Kim Soo Hyun Kim Hyun Jung Oh Hye Won Kang Seo Woo Kim Min-A Yu Dong-Ryeol Ryu Kyu-Bok Choi Duk-Hee Kang Department of Internal Medicine, Ewha Womans University College of Medicine 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. KEY WORDS:Acute kidney failure pulmonary edema Angiotensin-converting enzyme Inhibitors Angiotensin II Type 1 receptor blockers Congenital solitary kidney. 교신저자 : 강덕희, 서울양천구목동 이화여자대학교의학전문대학원내과학교실전화 :(02) 전송 :(02) dhkang@ewha.ac.kr

서론 안지오텐신전환효소억제제 (Angiotensin-converting enzyme inhibitor, ACEi) 와안지오텐신 II 수용체차단제 (Angiotensin II receptor blocker, ARB) 는고혈압, 심부전및단백뇨의치료에효과적인약물로널리사용되고있다 1-3).

2 서론 안지오텐신전환효소억제제 (Angiotensin-converting enzyme inhibitor, ACEi) 와안지오텐신 II 수용체차단제 (Angiotensin II receptor blocker, ARB) 는고혈압, 심부전및단백뇨의치료에효과적인약물로널리사용되고있다 1-3). 이들레닌-안지오텐신시스템차단제의중요한부작용가운데하나로신기능의악화를들수있는데특히, 양측신동맥협착이있거나신장이식등으로단일신을가진환자에서의편측신혈관협착또는저혈량상태등과같이체내의레닌-안지오텐신시스템의활성화에의해사구체여과율이유지되고있는환자에서심각한신기능저하가쉽게발생할수있기때문에투여에신중을기하고, 위와같은질환이확인된경우의사용은금기로되어있다 4). 따라서이들약제의투여를처음시작할때에는신체검사, 소변량측정및혈액검사등을통해신기능에대한평가를주의깊게하며투여를시작하여야한다 1-4). 저자들은이전에신장기능검사이외에신장에대한검사없이고혈압치료만받아왔던선천성단일신환자에서안지오텐신전환효소억제제와안지오텐신 II 수용체차단제치료를함께시작한후, 급격한신기능저하와급성폐부종이발생한 1예를경험하였기에보고하는바이다. 증례 알부민 4.3g/dL 이었고소변검사에서요비중 1.015, ph5.0, 혈뇨 (4+) 이었으나염증이나단백뇨소견은없었다. 흉부방사선, 신체검사, 활력징후에서감염성질환을시사하는소견은관찰되지않았다. 환자는천식의급성악화에의한호흡곤란진단하에살부타몰 (salbutamol) 4mg, 아젤란 (azelastine) 2mg 이처방되었으며, 혈압강하를위하여올메텍 (olmesartan) 20mg, 레니프릴 (enalapril) 10mg이라식스 (furosemide) 40mg과함께투여되었다. 환자는입원 3일째부터소변량이감소하기시작되어, 입원 5일째에본원으로전원되는날까지하루소변이 500cc 미만으로배출되었고고질소혈증이급격하게진행되었다. 본원으로전원되어시행한심장초음파에서심박출량정상범위였으며국소벽운동장애는관찰되지않았고, 이완기심부전소견도관찰되지않았다. 복부초음파에서좌신은관찰되지않았으며우신의크기는 9.9cm 으로피질의신병증소견이있었다 (Fig. 1). 환자는중환자실로입원하였으며안지오텐신전환효소억제제와안지오텐신 II 수용체차단제를중단하고라식스는유지하였다. 전원다음날부터환자의소변양은회복되었으나폐부종, 고질소혈증은더욱진행하였다 (Fig. 2). 입원 10일째혈중요질소와크레아티닌은 102/6.9mg/dL까지상승하며, 환자의식혼미해졌고요독성뇌병증진단하에혈액투석을시행하였다. 이후입원 20일째까지총 4회의혈액투석을시행하였고, 이후환자는라식스 320mg 경구투여로충분한소변양유지되면서폐부종및신기능의추가악화발생하지않아서입원 35일째퇴원하였다 (Fig. 3). 86세여성이소변량감소와호흡곤란을주소로타병원에서전원되었다. 환자는 30년전고혈압진단받고지역의원에서티아지드계이뇨제와베타차단제를복용중이던환자로혈액검사나복부전산화촬영, 복부초음파등의검사를해본적은없었다. 본원내원 5일전부터시작된호흡곤란을주소로타병원에입원하였고, 혈압은 180/100 mmhg로측정되었다. 말초혈액검사에서백혈구 7,300/mm 3 ( 호중구 :68%), 헤모글로빈 9.2g/dL, 헤마토크릿 26.6%, 혈소판 123,000/mm 3 이었다. 혈청화학검사에서나트륨 148mEq/L, 칼륨 4.5mEq/L, 염소 109mEq/L, 혈당 142mg/dL, 혈중요질소 46mg/dL, 크레아티닌 2.0mg/dL, 아스퍼테이트아미노전이효소 28IU/ L, 알라닌아미노전이효소 13IU/L, 단백질 7.0g/dL, Fig. 1. Abdomen sonography revealed an increased cortical echogenicity of right kidney with non-visible left kidney

고 안지오텐신 II는혈관수축작용을하는데특히, 콩팥의수출소동맥의수축을유발하여사구체여과율을증 Fig. 2. Chest AP revealed an increased interstitial density over both lung fields with cardiomegaly suggestive acute pulmonary edema(hospital day #8).

3 고 안지오텐신 II는혈관수축작용을하는데특히, 콩팥의수출소동맥의수축을유발하여사구체여과율을증 Fig. 2. Chest AP revealed an increased interstitial density over both lung fields with cardiomegaly suggestive acute pulmonary edema(hospital day #8). 찰 가시키며, 부신피질에서알도스테론을활성화시켜혈압을상승시킨다 1). 안지오텐신전환효소억제제와안지오텐신 II 수용체차단제는각각안지오텐신 II의생성억제하거나그작용을억제함으로써신수출소동맥의혈관수축을억제하여사구체여과율을감소시키며, 혈압을강하하고심혈관계의부하를감소시켜심장리모델링의반전을가져온다고알려져있어울혈성심부전, 당뇨성신부전, 고혈압등의치료제로널리쓰이고있다 1-4). 하지만이들약물의중요한부작용중의하나로급성신부전이발생될수있는데, 주로저혈량상태및양측신동맥의협착, 편측신혈관의협착등으로이미레닌-안지오텐신시스템이활성화되어사구체여과율이유지되는상태에서레닌-안지오텐신시스템차단제를사용하는경우쉽게급성신부전이유발되는것으로알려져있다 5-12). 1980년대이후안지오텐신전환효소억제제로인한신기능저하의기전이여러증례보고및동물실험에의해정립되었지만, 1990년대이후도입된안지오텐신 II 수용체차단제에대해서는충분한증례보고및실험을이루어지지못한상태이다. 이들약제에의한신기능저 cr (mg/dl) Uremic encephalopathy ACEi, ARB stop ACEi, ARB start U/O (ml) 1,500 1, Transfer HD HD HD HD Hospital day (day) Fig. 3. Changes in serum creatinine level and urine output of the patient. HD:hemodialysis, ACEi:angiotensin-converting enzyme inhibitor, ARB:angiotensin II receptor blocker

4 하에대한대부분의보고들은주로양측신동맥협착이있는경우이거나신장이식환자에서이식신의신동맥협착이발생한경우이며또는일측신이위축되어완전히기능을상실한상태에서정상신의신동맥협착이있는경우이었으며, 이환자의경우처럼선천성일측신인환자에서의증례보고는없었고또한안지오텐신전환효소억제제와안지오텐신 II 수용체차단제를같이투여하였을때발생한신부전의경과대한보고도매우드물었다 13). 또한선천성단일신의발생률은연구들에따라다르나, 보통인구집단에서 1/500~1/1,500 의비율로발생한다고보고되며 14)15), 본증례는이전에진단된적이없었던선천성단일신환자로서일측신의보상성초여과가이루어지고있는상태에서고리이뇨제투여로유도된저혈량상태에의해레닌-안지오텐신시스템이더욱활성화되었을것으로생각되고이상태에서안지오텐신전환효소억제제와안지오텐신 II 수용체차단제를투여하여급격한신기능저하가유발되었을것으로생각된다. 환자는치료초기에카베딜 (carvedilol) 25mg, 올메텍 (olmesartan) 20mg, 레니프릴 (enalapril) 20mg 을함께투여하였음에도불구하고수축기동맥압이 180 mmhg 이상으로잘조절되지않았던환자로신동맥협착의존재가능성도높다고생각되나, 조영제를사용하는영상의학적검사및신동맥확장술을시행할경우환자가말기신부전으로이행할가능성이높다고생각되어추가검사는시행하지는않았다. 안지오텐신전환효소억제제와안지오텐신 II 수용체차단제의치료를시작하는모든환자에서투여전에도플러초음파, MRI, 신장스캔등의영상의학검사를시행하여단일신및신동맥협착등의상태를파악할수는없을것이다. 하지만이전동맥경화질환이진단된적이있거나갑자기발생한잘조절되지않는고혈압, 원인불명의고질소혈증등이있는환자들은신동맥협착이있을가능성이높은환자들이다 16). 이러한신혈관질환을배제하기어려운환자에서는안지오텐신전환효소억제제와안지오텐신 II 수용체차단제의투여전신장및신혈관상태에대한평가를시행하는것이이약물의중대한합병증중하나인급격한신기능저하를예방하기위해서필요하다고사료된다. 중심단어 : 선천성단일신 급성신부전 안지오텐신변화요소억제제 안지오텐신 II 수용체차단제. References 1) Hilgers KF, Mann JF:ACE inhibitors versus AT(1) receptor antagonists in patients with chronic renal disease. J Am Soc Nephrol 2002;13: ) Baker KM, Booz GW, Dostal DE:Cardiac Actions of Angiotensin II:Role of an Intracardiac Renin-Angiotensin System. Annual Review of Physiology 1992; 54: ) Matchar DB, McCrory DC, Orlando LA, Patel MR, Patel UD, Patwardhan MB, et al:systematic review: comparative effectiveness of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers for treating essential hypertension. Ann Intern Med 2008; 148: ) Hricik DE, Dunn MJ:Angiotensin-converting enzyme inhibitor-induced renal failure: Causes, consequence and diagnostic uses. J Am Soc Nephrol 1990;1: ) Maillard TO, Descombes E, Fellay G, Reganey C:Repeated transient anuria following losartan administration in a patient with a solitary kidney. Ren Fail 2001; 23: ) Ostermann M, Goldsmith DJ, Doyle T, Kingswood JC, Sharpstone P:Reversible acute renal failure induced by losartan in a renal transplant recipient. Postgrad Med J 1997;73: ) Ahmet AK, Murat B, Caner O, Ahmet C, Altan Y:Two episode of anuria and acute pulmonary edema in a losartan-treated patient with solitary kidney Heart Vessels 2004;19: ) Johansen TL, Kjaer A:Reversible renal impairment induced by treatment with angiotensin II receptor antagonist candesartan in a patient with bilateral renal artery stenosis. BMC Nephrology 2001;2:1 9) Saine DR, Ahrens ER:Renal impairment associated with losartan. Ann Intern Med 1996;124:775 10) Holm EA, Randlov A, Strandguard S:Acute renal failure after losartan treatment in a patient with bilateral renal artery stenosis. Blood press 1996;5: ) Missouris CG, Ward DE, Eastwood JB, MacGregor GA:Deterioration in renal function with enalapril but not losartan in a patient with renal artery stenosis in a solitary kidney. Heart 1997;77: ) Cohen LS, Friedman EA:Losartan-induced azotemia in a diabetic recipient of a kidney transplantation. N

5 Engl J Med 1996;334: ) Wargo KA, Chong K, Chan EC:Acute renal failure secondary to Angiotensin II receptor blockade in a patient with bilateral renal artery stenosis. Pharmacotherapy 2003;23: ) Hiraoka M, Tsukahara H, Ohshima Y, Kasuga K:Renal aplasia is the predominant cause of congenital solitary kidneys. Kidney International 2002;61: ) Woolf AS, Hillman KA:Unilateral renal agenesis and the congenital solitary functioning kidney: developmental, genetic and clinical perspectives. BJU International 2006;99: ) Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL, et al:harrison s Principles of Internal Medicine. 17 th ed. USA Mc Graw Hill, 2005:

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심장2.PDF (Treatment of Hypertension with Associated Diseases) 1.. (140/90 mmhg). 80 mmhg. ( ). (atenolol ), (amlodipine ) 1. -1 nitrate. ACE diltiazem, verapamil. ACE. ( )., ACE diltiazem,, diltiazem, verapamil.