今日の臨床サポート

腎血管性高血圧症

著者: 平和伸仁 横浜市立大学附属市民総合医療センター 腎臓・高血圧内科/血液浄化療法部

監修: 岡田浩一 埼玉医科大学 腎臓内科

著者校正/監修レビュー済:2019/10/03
参考ガイドライン:
日本高血圧学会:高血圧治療ガイドライン2019(JSH2019)
患者向け説明資料

概要・推奨   

  1. 安静30分採血による血漿レニン活性(PRA)値は、必ずしも腎血管性高血圧の診断に有用ではない(推奨度2)
  1. 腎動脈狭窄を疑ったときは、腎動脈超音波検査(Duplex超音波法)を行う(推奨度1)
  1. 症例によってはMRAあるいは造影CTを行い、腎動脈狭窄を検索する。ただし、腎機能がeGFR30ml/分/1.73m2未満ではガドリニウムやヨード造影剤の使用を避け、非造影MRAを選択する(推奨度2)
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  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要とな
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となりま
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
平和伸仁 : 講演料(武田薬品工業)[2021年]
監修:岡田浩一 : 講演料(協和キリン,中外製薬,田辺三菱,第一三共),研究費・助成金など(協和キリン),奨学(奨励)寄付など(協和キリン,中外製薬,田辺三菱,第一三共,アステラス,MSD,武田薬品,鳥居薬品,ファイザー,ノバルティス,日本ベーリンガーインゲルハイム,大塚製薬,塩野義,大日本住友)[2021年]

改訂のポイント:
  1. JSH2019に基づき、診断手順の改訂を行った。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 腎血管性高血圧は、全高血圧患者の1%程度である。しかし、急速、重度、あるいは治療抵抗性高血圧の10~40%を占めるといわれている。
  1. 腎動脈の狭窄が原因で、腎灌流圧の低下によりレニンの過剰産生を生ずることにより発症する。
  1. 若年者では線維筋性異形成が、中・高年者では粥状動脈硬化が狭窄の原因となることが多い。
  1. 高レニン、高アルドステロンを呈する病態であり、低カリウム(K)血症および代謝性アルカローシスを生ずる。
  1. 重症高血圧や治療抵抗性高血圧を示す場合が多く、腹部血管雑音の有無に注意し、腎血流ドプラーがスクリーニング検査として有用である。
  1. 狭窄側の腎機能改善の可能性があれば、経皮的腎動脈形成術(PTRA)の適応を検討する。PTRAは、血圧管理には有用であるが、生命予後および腎保護効果のエビデンスは十分でない。
 
  1. 腎動脈狭窄を疑ったときは、腎動脈超音波検査(Duplex超音波法)を行う(推奨度1)
  1. duplex超音波法は非侵襲的な検査であり、慢性的な腎動脈の狭窄があると腎の萎縮が起こる。左右の腎臓の大きさに差が1.5cm以上あれば有意な萎縮と考えられ、慢性的な狭窄が疑われる。腎動脈の血流速度(duplex超音波法)の測定により腎動脈狭窄を診断できるため、スクリーニング法として推奨されている[1][2]。動脈造影検査と比較して、腎動脈狭窄の診断に対する感度は84~98%、特異度は62~99%とされている[2]。メタ解析によると造影CT検査およびガドリニウム造影MRA、3D-MRAに比較するとROCカーブで劣る[3]が、duplex超音波法は非侵襲的であることに有用性が勝っているうえ、低コストである。特にpeak systolic velocityを指標とすると、感度85%、特異度92%と高い精度が得られる[4]。ただし、正確な診断には検査の熟練を要する。
 
腎血管性高血圧のドプラー所見

右腎動脈の狭窄により、狭窄位の収縮期最高流速が180cm/秒以上を示す。

 
 
腎血管性高血圧の腎大動脈造影所見

a:右腎動脈起始部の狭窄所見
b:PTRAにより拡張し血流が改善している。
c:メディケア受給者における腎動脈ステント留置術の施行数

 
 
腹部大動脈縮窄症(mid-aortic syndrome)の腎血管造影所見

腹部大動脈縮窄症に伴い右腎動脈起始部が狭窄(上腸間膜動脈[SMA]も狭窄しており、下腸間膜動脈[IMA]が発達している)。

 
 
 
腎血管性高血圧のCTアンギオグラフィ(CTA)所見

a、b:右腎動脈の部分的血流の低下所見(腎梗塞)
c:左腎動脈狭窄に伴う左腎血流低下

 
問診・診察のポイント  
  1. 患者の発症年齢(30歳以下)から、線維筋性異形成の可能性を考える。

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文献 

著者: Kidney Disease Outcomes Quality Initiative (K/DOQI)
雑誌名: Am J Kidney Dis. 2004 May;43(5 Suppl 1):S1-290.
Abstract/Text
PMID 15114537  Am J Kidney Dis. 2004 May;43(5 Suppl 1):S1-290.
著者: Alan T Hirsch, Ziv J Haskal, Norman R Hertzer, Curtis W Bakal, Mark A Creager, Jonathan L Halperin, Loren F Hiratzka, William R C Murphy, Jeffrey W Olin, Jules B Puschett, Kenneth A Rosenfield, David Sacks, James C Stanley, Lloyd M Taylor, Christopher J White, John White, Rodney A White, Elliott M Antman, Sidney C Smith, Cynthia D Adams, Jeffrey L Anderson, David P Faxon, Valentin Fuster, Raymond J Gibbons, Sharon A Hunt, Alice K Jacobs, Rick Nishimura, Joseph P Ornato, Richard L Page, Barbara Riegel, American Association for Vascular Surgery, Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, ACC/AHA Task Force on Practice Guidelines Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease, American Association of Cardiovascular and Pulmonary Rehabilitation, National Heart, Lung, and Blood Institute, Society for Vascular Nursing, TransAtlantic Inter-Society Consensus, Vascular Disease Foundation
雑誌名: Circulation. 2006 Mar 21;113(11):e463-654. doi: 10.1161/CIRCULATIONAHA.106.174526.
Abstract/Text
PMID 16549646  Circulation. 2006 Mar 21;113(11):e463-654. doi: 10.1161・・・
著者: G B Vasbinder, P J Nelemans, A G Kessels, A A Kroon, P W de Leeuw, J M van Engelshoven
雑誌名: Ann Intern Med. 2001 Sep 18;135(6):401-11.
Abstract/Text PURPOSE: To summarize and compare the validity of computed tomography angiography, magnetic resonance angiography, ultrasonography, captopril renal scintigraphy, and the captopril test for diagnosis of renal artery stenosis in patients suspected of having renovascular hypertension.
DATA SOURCES: For each diagnostic modality, published studies were identified by MEDLINE literature searches.
STUDY SELECTION: Original studies were selected if they met the following criteria: 1) suspicion of renovascular hypertension was the indication for the test; 2) intra-arterial x-ray angiography was used as the gold standard; 3) a cutoff point for a positive test result was explicitly defined; and 4) absolute numbers of true-positive, false-negative, true-negative, and false-positive results were available or could be derived from the presented data.
DATA EXTRACTION: A standard form was used to extract relevant data.
DATA SYNTHESIS: Data on the accuracy of the different diagnostic methods were analyzed and compared by constructing summary receiver-operating characteristic (ROC) curves and by computing areas under the summary ROC curves.
RESULTS: Although accuracy varied greatly for all diagnostic modalities, summary ROC curves found that computed tomography angiography and gadolinium-enhanced, three-dimensional magnetic resonance angiography performed significantly better than the other diagnostic tests.
CONCLUSIONS: Computed tomography angiography and gadolinium-enhanced three-dimensional magnetic resonance angiography seem to be preferred in patients referred for evaluation of renovascular hypertension. However, because few studies of these tests have been published, further research is recommended.

PMID 11560453  Ann Intern Med. 2001 Sep 18;135(6):401-11.
著者: Gabrielle J Williams, Petra Macaskill, Siew F Chan, Thomas E Karplus, Winkle Yung, Elisabeth M Hodson, Jonathan C Craig
雑誌名: AJR Am J Roentgenol. 2007 Mar;188(3):798-811. doi: 10.2214/AJR.06.0355.
Abstract/Text OBJECTIVE: The purpose of this study was to evaluate the test performance of duplex sonographic parameters in screening for hemodynamically significant renal artery stenosis, which occurs in approximately 5% of persons with hypertension.
MATERIALS AND METHODS: A comprehensive literature search was conducted to find studies on the diagnosis of renal artery stenosis in which duplex sonography and intraarterial angiography were compared and in which sensitivity and specificity were calculated. MEDLINE (1966-2005), EMBASE (1988-2005), and reference lists were searched and the authors contacted. Data were subjected to meta-analysis according to the hierarchical summary receiver operating characteristic curve model. Heterogeneity in test performance relating to population and design features was investigated.
RESULTS: From 1,357 titles, 88 studies involving 9,974 arteries in 8,147 patients were included. The following four parameters were evaluated: peak systolic velocity (21 studies), acceleration time (13 studies), acceleration index (13 studies), and renal-aortic ratio (13 studies). The corresponding diagnostic odds ratios (ORs) were 60.9 (95% CI, 28.3-131.2), 28.9 (95% CI, 7.1-117.2), 16.0 (95% CI, 5.1-50.6), and 29.3 (95% CI, 12.7-67.7). Results based on studies in which parameters were directly compared showed that peak systolic velocity had greater accuracy than renal-aortic ratio (relative diagnostic OR, 1.8; p = 0.03; nine studies) and acceleration index (relative diagnostic OR, 5.3; p < 0.001; five studies). Acceleration time versus acceleration index showed no evidence of a difference in accuracy (relative diagnostic OR, 1.1; p = 0.65; nine studies). Analysis of peak systolic velocity used in combination with other parameters compared with peak systolic velocity alone (seven studies) showed evidence of a shift in test positivity (p < 0.001) but only weak evidence of improvement in accuracy (relative diagnostic OR, 1.6; p = 0.09).
CONCLUSION: Sonography is a moderately accurate screening test for renal artery stenosis. The single measurement, peak systolic velocity, has the highest performance characteristics, an expected sensitivity of 85% and specificity of 92%. Additional measurements do not increase accuracy.

PMID 17312071  AJR Am J Roentgenol. 2007 Mar;188(3):798-811. doi: 10.2・・・
著者: F B Muller, J E Sealey, D B Case, S A Atlas, T G Pickering, M S Pecker, J J Preibisz, J H Laragh
雑誌名: Am J Med. 1986 Apr;80(4):633-44.
Abstract/Text To develop a screening test for identifying renovascular hypertension, the blood pressure and plasma renin activity responses to an oral test dose of captopril were studied in 246 quietly seated hypertensive patients. The following criteria were developed that exploit the hyperresponsiveness of renin secretion in renovascular hypertensive patients: a 60-minute post-captopril plasma renin activity of 12 ng/ml per hour or more and an absolute plasma renin activity increase of 10 ng/ml per hour or more, along with a 150 percent increase in plasma renin activity (or a 400 percent increase if the baseline plasma renin activity was below 3 ng/ml per hour). Retrospectively, the test identified, among 200 hypertensive patients without evidence of renal dysfunction, all 56 patients with proved renovascular disease. In this group, false-positive results occurred only in two of 112 patients with essential hypertension and in six with secondary hypertension. Nine untreated patients had blood pressure levels of less than 160/100 mm Hg. The test was neither as sensitive nor specific in the 46 patients with renal insufficiency. This study demonstrates that the renin response to oral captopril is a useful screening test for identifying patients with unilateral or bilateral renovascular disease. Since the test also characterizes the renin dependency of the hypertension, it may have other diagnostic and therapeutic uses.

PMID 3515933  Am J Med. 1986 Apr;80(4):633-44.
著者: S J Mann, T G Pickering, T A Sos, R G Uzzo, S Sarkar, K Friend, M E Rackson, J H Laragh
雑誌名: Am J Med. 1991 Jan;90(1):30-40.
Abstract/Text PURPOSE: The purpose of this study was to determine the sensitivity, specificity, and clinical usefulness of renography performed in combination with captopril administration ("captopril renography") in diagnosing renal artery stenosis.
PATIENTS AND METHODS: Fifty-five patients with suspected renal artery stenosis underwent renography prior to performance of renal angiography. Renography was performed on two consecutive days using technetium-99m-diethylenetiamine pentaacetic acid (DTPA) as an index of glomerular filtration rate and iodine-131-orthoiodohippurate (OIH) as an index of renal blood flow. Captopril (25 mg orally, crushed) was administered 1 hour before the second study. Renal artery stenosis was defined as a stenosis exceeding 70%. Renographic criteria were then established, retrospectively, to differentiate renal artery stenosis from essential hypertension based on (1) asymmetry of function and (2) the presence of captopril-induced changes.
RESULTS: Renal artery stenosis was detected in 35 of 55 patients (21 with unilateral and 14 with bilateral stenosis). Three criteria were established for diagnosing renal artery stenosis: (1) a percent uptake of DTPA by the affected kidney of less than 40% of the combined bilateral uptake, (2) a delayed time to peak uptake of DTPA, which was more than 5 minutes longer in the affected kidney than in the contralateral kidney, (3) a delayed excretion of DTPA, with retention at 15 minutes, as a fraction of peak activity, more than 20% greater than in the contralateral kidney. The presence of one or more of these criteria was diagnostic of renal artery stenosis, with a sensitivity and specificity of 71% and 75%, respectively before captopril administration, and 94% and 95% after captopril administration. Lesser degrees of asymmetry (i.e., uptake of 40% to 50%) had very poor diagnostic specificity. Among patients with bilateral stenoses, asymmetry identified the more severely affected kidney, but the presence or absence of stenosis in the contralateral kidney could not be reliably determined. When pre- and post-captopril studies were compared, the presence of captopril-induced scintigraphic changes was a highly specific finding for renal artery stenosis, but occurred in only 51% of the cases. OIH scintigraphy provided similar results, with slightly lower sensitivity and specificity.
CONCLUSION: Asymmetry of DTPA uptake, time to peak uptake, or retention seen on a single post-captopril renogram is a highly sensitive and specific finding in detecting renal artery stenosis but does not distinguish unilateral from bilateral disease. If renograms are obtained both before and after captopril administration, the presence of captopril-induced change is a highly specific finding for the detection of renal artery stenosis, but the sensitivity of this finding is low.

PMID 1986590  Am J Med. 1991 Jan;90(1):30-40.
著者: Stephen J Huot, Joni H Hansson, Holly Dey, John Concato
雑誌名: Arch Intern Med. 2002 Sep 23;162(17):1981-4.
Abstract/Text BACKGROUND: Captopril renal scanning (CRS) is commonly recommended as a noninvasive method for detecting renal artery stenosis (RAS), based on performance characteristics determined in research settings. Scant data are available, however, regarding the utility of CRS in clinical practice.
METHODS: We evaluated the performance characteristics (sensitivity, specificity, and predictive values) of CRS in a consecutive series of 90 patients who underwent both CRS and renal arteriography within a 6-month period (January 1, 1991, through December 31, 1995) at a university hospital.
RESULTS: Among 86 eligible patients (and 169 kidneys), the prevalence of RAS was 43%. The sensitivity of CRS was 74% (95% confidence interval [CI], 62%-83%); the specificity was 59% (95% CI, 49%-69%); the positive predictive value was 58% (95% CI, 47%-68%); and the negative predictive value was 75% (95% CI, 64%-84%). Also, there was evidence of spectrum bias, because the sensitivity and specificity (as well as the positive and negative predictive values) were different for groups with and without vascular disease.
CONCLUSIONS: The results of CRS were substantially worse in a clinical practice setting than previously reported in research settings, despite a similar prevalence of RAS. Captopril renal scanning should not be used as an initial screening test for diagnosing RAS, even among patients with high clinical likelihood of disease.

PMID 12230421  Arch Intern Med. 2002 Sep 23;162(17):1981-4.
著者: J E Sealey, F R Bühler, J H Laragh, E D Vaughan
雑誌名: Am J Med. 1973 Sep;55(3):391-401.
Abstract/Text
PMID 4746559  Am J Med. 1973 Sep;55(3):391-401.
著者: E D Vaughan
雑誌名: Kidney Int. 1985 May;27(5):811-27.
Abstract/Text
PMID 3160883  Kidney Int. 1985 May;27(5):811-27.
著者: Henrik S Thomsen, European Society of Urogenital Radiology (ESUR)
雑誌名: Eur Radiol. 2007 Oct;17(10):2692-6.
Abstract/Text
PMID 17977076  Eur Radiol. 2007 Oct;17(10):2692-6.
著者: G Boudewijn C Vasbinder, Patricia J Nelemans, Alfons G H Kessels, Abraham A Kroon, Jeffrey H Maki, Tim Leiner, Frederik J A Beek, Michael B J M Korst, Karin Flobbe, Michiel W de Haan, Willem H van Zwam, Cornelis T Postma, M G Myriam Hunink, Peter W de Leeuw, Jos M A van Engelshoven, Renal Artery Diagnostic Imaging Study in Hypertension (RADISH) Study Group
雑誌名: Ann Intern Med. 2004 Nov 2;141(9):674-82; discussion 682.
Abstract/Text BACKGROUND: Timely, accurate detection of renal artery stenosis is important because this disorder may be a potentially curable cause of hypertension and renal impairment.
OBJECTIVE: To determine the validity of computed tomographic angiography (CTA) and magnetic resonance angiography (MRA) compared with digital subtraction angiography (DSA) for detection of renal artery stenosis.
DESIGN: Prospective multicenter comparative study conducted from 1998 to 2001. Two panels of 3 observers judged CTA and MRA image data and were blinded to all other results. Digital subtraction angiography images were evaluated by consensus.
SETTING: 3 large teaching hospitals and 3 university hospitals in the Netherlands.
PATIENTS: 402 hypertensive patients with suspected renal artery stenosis were included. A group of 356 patients who underwent all 3 diagnostic tests was used for analysis.
MEASUREMENTS: Reproducibility was assessed by calculating interobserver agreement. Diagnostic performance was evaluated in terms of sensitivity, specificity, and other diagnostic variables. Atherosclerotic stenoses of 50% or greater and fibromuscular dysplasia were considered clinically relevant.
RESULTS: Twenty percent of patients who underwent all 3 tests had clinically relevant renal artery stenosis. Moderate interobserver agreement was found, with kappa values ranging from 0.59 to 0.64 for CTA and 0.40 to 0.51 for MRA. The combined sensitivity and specificity were 64% (95% CI, 55% to 73%) and 92% (CI, 90% to 95%) for CTA and 62% (CI, 54% to 71%) and 84% (CI, 81% to 87%) for MRA.
LIMITATIONS: Eighteen percent of the patients were included nonconsecutively. Digital subtraction angiography may be an imperfect reference test.
CONCLUSION: Computed tomographic angiography and MRA are not reproducible or sensitive enough to rule out renal artery stenosis in hypertensive patients. Therefore, DSA remains the diagnostic method of choice. *For a list of the other investigators and research coordinators who participated in RADISH, see the Appendix.

PMID 15520423  Ann Intern Med. 2004 Nov 2;141(9):674-82; discussion 68・・・
著者: P S Parfrey, S M Griffiths, B J Barrett, M D Paul, M Genge, J Withers, N Farid, P J McManamon
雑誌名: N Engl J Med. 1989 Jan 19;320(3):143-9. doi: 10.1056/NEJM198901193200303.
Abstract/Text To determine the risk of nephrotoxicity induced by the infusion of radiographic contrast material, we undertook a prospective study of consecutive patients undergoing radiographic procedures with intravascular contrast material. There were three study groups: patients with diabetes mellitus and normal renal function (n = 85), patients with preexisting renal insufficiency (serum creatinine level, greater than or equal to 150 mumol per liter) without diabetes (n = 101), and patients with both diabetes and renal insufficiency (n = 34). The control group consisted of patients undergoing CT scanning or abdominal imaging procedures without the infusion of contrast material who had diabetes mellitus (n = 59), preexisting renal insufficiency (n = 145), or both (n = 64). Clinically important acute renal failure (defined as an increase of greater than 50 percent in the serum creatinine level) attributable to the contrast material did not occur in nondiabetic patients with preexisting renal insufficiency or in diabetics with normal renal function. The incidence of clinically important contrast-induced renal failure among the diabetic patients with preexisting renal insufficiency was 8.8 percent (95 percent confidence interval, 1.9 to 23.7 percent), as compared with 1.6 percent for the controls. The incidence of acute renal insufficiency, more broadly defined as an increase of greater than 25 percent in the serum creatinine level after the infusion of contrast material, was 11.8 percent among all patients with preexisting renal insufficiency. After the exclusion of patients whose acute renal insufficiency could be attributed to other causes, the incidence was 7.0 percent (95 percent confidence interval, 3.2 to 12.8 percent), as compared with 1.5 percent in the control group. The risk of acute renal insufficiency attributable to the contrast material was therefore 5.5 percent, and the relative risk associated with the infusion of contrast material was 4.7. These rates were similar whether the osmolarity of the contrast material was high or low. We conclude that there is little risk of clinically important nephrotoxicity attributable to contrast material for patients with diabetes and normal renal function or for nondiabetic patients with preexisting renal insufficiency. The risk for those with both diabetes and preexisting renal insufficiency is about 9 percent, which is lower than previously reported.

PMID 2643041  N Engl J Med. 1989 Jan 19;320(3):143-9. doi: 10.1056/NE・・・
著者: Charanjit S Rihal, Stephen C Textor, Diane E Grill, Peter B Berger, Henry H Ting, Patricia J Best, Mandeep Singh, Malcolm R Bell, Gregory W Barsness, Verghese Mathew, Kirk N Garratt, David R Holmes
雑誌名: Circulation. 2002 May 14;105(19):2259-64.
Abstract/Text BACKGROUND: In patients undergoing percutaneous coronary intervention (PCI) in the modern era, the incidence and prognostic implications of acute renal failure (ARF) are unknown.
METHODS AND RESULTS: With a retrospective analysis of the Mayo Clinic PCI registry, we determined the incidence of, risk factors for, and prognostic implications of ARF (defined as an increase in serum creatinine [Cr] >0.5 mg/dL from baseline) after PCI. Of 7586 patients, 254 (3.3%) experienced ARF. Among patients with baseline Cr <2.0, the risk of ARF was higher among diabetic than nondiabetic patients, whereas among those with a baseline Cr >2.0, all had a significant risk of ARF. In multivariate analysis, ARF was associated with baseline serum Cr, acute myocardial infarction, shock, and volume of contrast medium administered. Twenty-two percent of patients with ARF died during the index hospitalization compared with only 1.4% of patients without ARF (P<0.0001). After adjustment, ARF remained strongly associated with death. Among hospital survivors with ARF, 1- and 5-year estimated mortality rates were 12.1% and 44.6%, respectively, much greater than the 3.7% and 14.5% mortality rates in patients without ARF (P<0.0001).
CONCLUSIONS: The overall incidence of ARF after PCI is low. Diabetic patients with baseline Cr values <2.0 mg/dL are at higher risk than nondiabetic patients, whereas all patients with a serum Cr >2.0 are at high risk for ARF. ARF was highly correlated with death during the index hospitalization and after dismissal.

PMID 12010907  Circulation. 2002 May 14;105(19):2259-64.
著者: Attilio Losito, Rosa Errico, Paola Santirosi, Tommaso Lupattelli, Giovanni Battista Scalera, Luciano Lupattelli
雑誌名: Nephrol Dial Transplant. 2005 Aug;20(8):1604-9. doi: 10.1093/ndt/gfh865. Epub 2005 May 3.
Abstract/Text BACKGROUND: Patients with atherosclerotic renovascular disease (ARVD) are almost invariably treated by revascularization. However, the long-term outcomes of this approach on survival and progression to renal failure have not been investigated and have not been compared with that of a purely medical treatment. The aim of this observational study was to investigate factors affecting long-term (over 5 years) outcome, survival and renal function of patients with ARVD treated invasively or medically.
METHODS: ARVD was demonstrated angiographically in 195 patients who were consecutively enrolled into a follow-up study. Patient age was 65.6+/-11.2 years, serum creatinine was 1.74+/-1.22 mg/dl and renal artery lumen narrowing was 73.5+/-17.5%. A revascularization was performed in 136 patients, whereas 54 subjects having comparable characteristics were maintained on a medical treatment throughout the study; five patients were lost during follow-up.
RESULTS: The main follow-up was 54.4+/-40.4 months. The assessment of cardiovascular survival and renal survival at the end of follow-up revealed 46 cardiovascular deaths, 20 patients with end-stage renal disease (ESRD) and 41 patients with an increase in serum creatinine of over one-third. The multivariate analysis showed that renal revascularization did not affect mortality or renal survival compared with medical treatment. Revascularization produced slightly lower increases in serum creatinine and a better control of blood pressure. A longer survival was associated with the use of angiotensin-converting enzyme inhibitors (ACEIs) (P = 0.002) in both revascularized and medically treated patients. The only significant predictor of ESRD was an abnormal baseline serum creatinine.
CONCLUSIONS: On long-term follow-up, ARVD was associated with a poor prognosis due to a high cardiovascular mortality and a high rate of ESRD. In our non-randomized study, revascularization was not a major advantage over medical treatment in terms of mortality or renal survival. The use of ACEIs was associated with improved survival.

PMID 15870215  Nephrol Dial Transplant. 2005 Aug;20(8):1604-9. doi: 10・・・
著者: Daniel G Hackam, Minh L Duong-Hua, Muhammad Mamdani, Ping Li, Sheldon W Tobe, J David Spence, Amit X Garg
雑誌名: Am Heart J. 2008 Sep;156(3):549-55. doi: 10.1016/j.ahj.2008.05.013. Epub 2008 Jul 21.
Abstract/Text BACKGROUND: Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers effectively reduce blood pressure in patients with renovascular disease (RVD); yet, randomized cardiovascular prevention trials of these drugs typically exclude individuals with this condition.
PATIENTS AND METHODS: We studied the association of renin-angiotensin system inhibition with prognosis in a population-based cohort comprising 3,570 patients with RVD in Ontario, Canada; slightly more than half (n = 1,857, 53%) were prescribed angiotensin inhibitors. The primary outcome was the composite of death, myocardial infarction, or stroke. Secondary outcomes included individual cardiovascular and renal events.
RESULTS: Patients receiving angiotensin inhibitors had a significantly lower risk for the primary outcome during follow-up (10.0 vs 13.0 events per 100 patient-years at risk, multivariable adjusted hazard ratio [HR] 0.70, 95% CI 0.59-0.82). In addition, hospitalization for congestive heart failure (HR 0.69, 95% CI 0.53-0.90), chronic dialysis initiation (HR 0.62, 95% CI 0.42-0.92), and mortality (HR 0.56, 95% CI 0.47-0.68) was lower in treated patients. Conversely, patients receiving angiotensin inhibitors were significantly more likely to be hospitalized for acute renal failure during follow-up (HR 1.87, 95% CI 1.05-3.33; 1.2 vs 0.6 events per 100 patient-years at risk).
CONCLUSIONS: These data emphasize the high vascular risk of RVD and suggest that angiotensin inhibitors may improve prognosis in this setting at the expense of acute renal toxicity. If the latter are selected in the management of RVD, renal function parameters should be assiduously followed.

PMID 18760140  Am Heart J. 2008 Sep;156(3):549-55. doi: 10.1016/j.ahj.・・・
著者: K P Cicuto, G K McLean, J A Oleaga, D B Freiman, R A Grossman, E J Ring
雑誌名: AJR Am J Roentgenol. 1981 Sep;137(3):599-601. doi: 10.2214/ajr.137.3.599.
Abstract/Text Most lesions that decrease renal blood flow originate within the renal artery; however; large, aortic, atherosclerotic plaques can overhang the renal ostium producing a functional renal artery stenosis. At the Hospital of the University of Pennsylvania, 45 consecutive percutaneous transluminal angioplasties were examined retrospectively and classified as to site of the obstructing lesions and clinical outcome. Stenoses within the renal artery responded very well to angioplasty, with 83% of patients showing either an excellent or good result. Conversely, when aortic plaques were responsible for inflow obstruction, 76% of patients responded poorly or not at all to balloon dilatation. It is proposed that this disparity of response reflects the anatomic differences in the orientation of elastic and collagen fibers of the muscularis and advential layers of the renal artery and the aorta.

PMID 6456652  AJR Am J Roentgenol. 1981 Sep;137(3):599-601. doi: 10.2・・・
著者: L A Brawn, L E Ramsay
雑誌名: Lancet. 1987 Dec 5;2(8571):1313-6.
Abstract/Text 58 hypertensive patients with suspected renovascular disease underwent renal arteriography, and 29 (52%) were found to have renovascular disease. Percutaneous transluminal angioplasty was technically successful in 14 (50%) of the 29. The effect on blood pressure was assessed over 20 months. Technically successful transluminal angioplasty led to cure of hypertension in 4 patients (29%) and "improvement" in 5 (36%). However, "improvement" occurred spontaneously in 8 (32%) of the 25 patients found on arteriography not to have renovascular disease and who received no intervention. This suggests that reported improvement after transluminal angioplasty may be spurious and that the true benefit of the procedure can be assessed only from the cure rate. About 50% of patients with fibromuscular renovascular disease are cured of their hypertension but only about 8% of patients with atherosclerotic renovascular disease benefit from the procedure.

PMID 2890911  Lancet. 1987 Dec 5;2(8571):1313-6.
著者: C J Tegtmeyer, J B Selby, G D Hartwell, C Ayers, V Tegtmeyer
雑誌名: Circulation. 1991 Feb;83(2 Suppl):I155-61.
Abstract/Text Percutaneous transluminal angioplasty (PTA) was used to treat 66 patients with 85 renal artery stenoses due to fibromuscular dysplasia. The hypertension was refractory to medical management in 46 patients, and the initial success rate was 100%. Clinical follow-up has been obtained in all patients, who were followed for as long as 121 months. The recurrence rates were 8% of lesions and 10% of patients. Cumulative patency rate predicted for 10 years was 87.07%. The mean systolic pressure decreased by 52 mm Hg and the mean diastolic pressure decreased by 35 mm Hg in response to treatment. Twenty-six patients (39%) were cured, 39 (59%) were classified as improved, and one (2%) did not respond to PTA. Fourteen of the patients also had elevated blood urea nitrogen and creatinine levels. Renal function was improved in 86% of the patients and stabilized in 14% of the patients. Analysis of the long-term results suggests that PTA should be the initial treatment for choice of patients with fibromuscular dysplasia in the renal arteries.

PMID 1825043  Circulation. 1991 Feb;83(2 Suppl):I155-61.
著者: A Alhadad, I Mattiasson, K Ivancev, A Gottsäter, B Lindblad
雑誌名: J Hum Hypertens. 2005 Oct;19(10):761-7. doi: 10.1038/sj.jhh.1001893.
Abstract/Text Fibromuscular dysplasia (FMD) mainly affects renal arteries. Percutaneous transluminal renal angioplasty (PTRA) and surgery are effective treatments, but long-time follow-up is lacking. Retrospective follow-up for 7.0+/-4.7 years of 69 consecutive patients (age 44+/-13 years) treated for hypertension due to FMD, 59 patients underwent PTRA and eight patients surgery. In two patients no PTRA was performed. Technical success was achieved in 56 (95%) patients undergoing PTRA and all eight undergoing surgery. After successful PTRA, both systolic and diastolic blood pressures (SBP and DBP) had decreased at discharge (from 174+/-33/100+/-13 to 138+/-19/80+/-15 mmHg; P<0.0001), and remained lower at 1 month, 1 year, and last follow-up after 7.0+/-4.7 years (140+/-25/83+/-12 mmHg; P<0.0001). Serum-creatinine had decreased both at 1 year (from 84+/-28 to 75+/-13 micromol/l; P=0.0030) and last follow-up (75+/-16 micromol/l; P=0.0017). The number of antihypertensive drugs decreased (from 2.3+/-1.2 before PTRA to 1.4+/-1.3 at discharge and at 1 month; P<0.0001, and 1.6+/-1.5 at last follow-up; P=0.0011). SBP decreased more after PTRA among patients with FMD only in the main renal artery than in those with branch artery involvement (43+/-29 vs 20+/-41 mmHg; P=0.0198). Beneficial effects on BP, creatinine and antihypertensive drugs also occurred after surgery. Patients on antihypertensive drugs at last follow-up had longer hypertension duration before PTRA than those without (5.9+/-7.7 vs 1.8+/-4.1 years; P=0.0349). Cure was achieved in 16 (24%), improvement in another 26(39%), and benefit in 42(63%). In conclusion, renal artery FMD, PTRA and surgery have beneficial long-term effects, negatively affected by hypertension duration and branch artery involvement.

PMID 15920452  J Hum Hypertens. 2005 Oct;19(10):761-7. doi: 10.1038/sj・・・
著者: Albeir Y Mousa, John E Campbell, Patrick A Stone, Mike Broce, Mark C Bates, Ali F AbuRahma
雑誌名: J Vasc Surg. 2012 Feb;55(2):421-7. doi: 10.1016/j.jvs.2011.09.006. Epub 2011 Nov 23.
Abstract/Text OBJECTIVES: The purpose of this study was to evaluate short and long-term outcomes of percutaneous transluminal intervention in patients with symptomatic renal artery stenosis due to fibromuscular dysplasia (RAFMD) and/or the combination of RAFMD with aorto-ostial atherosclerotic disease.
METHODS: A retrospective analysis of all patients with renal artery RAFMD who underwent transcatheter therapy between January 1999 and December 2009 was performed. Blood pressure (BP) measurement, number of BP medications, and hypertension defined by a systolic BP >140 ± diastolic BP >90 were recorded. Renal function was defined by estimated glomerular filtration rate (eGFR). Restenosis was defined by stenosis >60% and was determined by renal artery duplex and/or angiography. Freedom from event (restenosis, renal failure, or recurrent hypertension) was performed using life table analysis.
RESULTS: Forty-three procedures were performed on 35 patients with RAFMD. Thirty-two patients (91%) were women, with mean age of 61.9 years old. Technical success was 100% with adjunctive stent placement required in the FMD segment for dissection in 1 patient (2.3%) and in the non-FMD aorto-ostial atherosclerotic lesion in 4 patients (9.3%). Short-term outcomes: the majority (69%) had an immediate clinical benefit for hypertension, 6% were cured without BP medications, and 63% improved with less than or equal to preoperative BP medications. Postintervention, 17% remained at moderately reduced renal function (<60), whereas the percent above >60 mL/minute eGFR increased significantly (from 51% to 69%; P = .002). For the entire cohort, renal function (mean eGFR) significantly increased from 71.9 mL/minute + 5.8 to 80.8 mL/minute + 5.2 (P = .007). Long-term outcomes: freedom from recurrent or worsening hypertension (>140 systolic blood pressure [SBP] and >90 diastolic blood pressure [DBP]) was (93%, 75%, and 41%) and freedom from reduced renal function (eGFR <30 mL/minute) was (100%, 95%, and 64%) at 1, 5, and 8 years, respectively. Patients with reduced baseline renal function (<60 mL/minute) and combined atherosclerotic disease were more likely to experience long-term reduced renal function (eGFR <30 mL/minute; P = .003). Primary and assisted primary patency was (95%, 71%, and 50%) and (100%, 100%, and 100%) at 1, 5, and 9 years, respectively.
CONCLUSION: Renal angioplasty is a safe and durable modality for treating RAFMD with favorable short and long-term clinical outcomes. Patients with combined atherosclerotic disease and FMD were older and were more likely to have declining renal function over time. Early intervention may be imperative to achieve possible cure of hypertension.

Copyright © 2012 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.
PMID 22112553  J Vasc Surg. 2012 Feb;55(2):421-7. doi: 10.1016/j.jvs.2・・・
著者: R A Davidson, Y Barri, C S Wilcox
雑誌名: Am J Kidney Dis. 1996 Sep;28(3):334-8.
Abstract/Text Patients with fibromuscular dysplasia (FMD) and hypertension are frequently treated with percutaneous transluminal renal angioplasty (PTRA). Because the goal of this procedure is the cure of hypertension, we reviewed the outcomes of 23 consecutive patients undergoing this procedure to determine factors associated with cure. Twelve (52.2%) of the patients were taking no antihypertensive medications at 6 months and were classified as cured. Using logistic regression, we found three variables to be independently associated with cure: level of systolic blood pressure before intervention (P = 0.02), duration of hypertension (P = 0.03), and age (P = 0.03). Younger patients with milder hypertension of a shorter duration were most likely to be cured. Analysis of the regression equation predicts that some patients with an extremely low chance of cure might be managed with a trial of medical therapy, because FMD is unlikely to progress to renal failure.

PMID 8804230  Am J Kidney Dis. 1996 Sep;28(3):334-8.
著者: B C van Jaarsveld, P Krijnen, H Pieterman, F H Derkx, J Deinum, C T Postma, A Dees, A J Woittiez, A K Bartelink, A J Man in 't Veld, M A Schalekamp
雑誌名: N Engl J Med. 2000 Apr 6;342(14):1007-14. doi: 10.1056/NEJM200004063421403.
Abstract/Text BACKGROUND: Patients with hypertension and renal-artery stenosis are often treated with percutaneous transluminal renal angioplasty. However, the long-term effects of this procedure on blood pressure are not well understood.
METHODS: We randomly assigned 106 patients with hypertension who had atherosclerotic renal-artery stenosis (defined as a decrease in luminal diameter of 50 percent or more) and a serum creatinine concentration of 2.3 mg per deciliter (200 micromol per liter) or less to undergo percutaneous transluminal renal angioplasty or to receive drug therapy. To be included, patients also had to have a diastolic blood pressure of 95 mm Hg or higher despite treatment with two antihypertensive drugs or an increase of at least 0.2 mg per deciliter (20 micromol per liter) in the serum creatinine concentration during treatment with an angiotensin-converting-enzyme inhibitor. Blood pressure, doses of antihypertensive drugs, and renal function were assessed at 3 and 12 months, and patency of the renal artery was assessed at 12 months.
RESULTS: At base line, the mean (+/-SD) systolic and diastolic blood pressures were 179+/-25 and 104+/-10 mm Hg, respectively, in the angioplasty group and 180+/-23 and 103+/-8 mm Hg, respectively, in the drug-therapy group. At three months, the blood pressures were similar in the two groups (169+/-28 and 99+/-12 mm Hg, respectively, in the 56 patients in the angioplasty group and 176+/-31 and 101+/-14 mm Hg, respectively, in the 50 patients in the drug-therapy group; P=0.25 for the comparison of systolic pressure and P=0.36 for the comparison of diastolic pressure between the two groups); at the time, patients in the angioplasty group were taking 2.1+/-1.3 defined daily doses of medication and those in the drug-therapy group were taking 3.2+/-1.5 daily doses (P<0.001). In the drug-therapy group, 22 patients underwent balloon angioplasty after three months because of persistent hypertension despite treatment with three or more drugs or because of a deterioration in renal function. According to intention-to-treat analysis, at 12 months, there were no significant differences between the angioplasty and drug-therapy groups in systolic and diastolic blood pressures, daily drug doses, or renal function.
CONCLUSIONS: In the treatment of patients with hypertension and renal-artery stenosis, angioplasty has little advantage over antihypertensive-drug therapy.

PMID 10749962  N Engl J Med. 2000 Apr 6;342(14):1007-14. doi: 10.1056/・・・
著者: ASTRAL Investigators, Keith Wheatley, Natalie Ives, Richard Gray, Philip A Kalra, Jonathan G Moss, Colin Baigent, Susan Carr, Nicholas Chalmers, David Eadington, George Hamilton, Graham Lipkin, Anthony Nicholson, John Scoble
雑誌名: N Engl J Med. 2009 Nov 12;361(20):1953-62. doi: 10.1056/NEJMoa0905368.
Abstract/Text BACKGROUND: Percutaneous revascularization of the renal arteries improves patency in atherosclerotic renovascular disease, yet evidence of a clinical benefit is limited.
METHODS: In a randomized, unblinded trial, we assigned 806 patients with atherosclerotic renovascular disease either to undergo revascularization in addition to receiving medical therapy or to receive medical therapy alone. The primary outcome was renal function, as measured by the reciprocal of the serum creatinine level (a measure that has a linear relationship with creatinine clearance). Secondary outcomes were blood pressure, the time to renal and major cardiovascular events, and mortality. The median follow-up was 34 months.
RESULTS: During a 5-year period, the rate of progression of renal impairment (as shown by the slope of the reciprocal of the serum creatinine level) was -0.07x10(-3) liters per micromole per year in the revascularization group, as compared with -0.13x10(-3) liters per micromole per year in the medical-therapy group, a difference favoring revascularization of 0.06x10(-3) liters per micromole per year (95% confidence interval [CI], -0.002 to 0.13; P=0.06). Over the same time, the mean serum creatinine level was 1.6 micromol per liter (95% CI, -8.4 to 5.2 [0.02 mg per deciliter; 95% CI, -0.10 to 0.06]) lower in the revascularization group than in the medical-therapy group. There was no significant between-group difference in systolic blood pressure; the decrease in diastolic blood pressure was smaller in the revascularization group than in the medical-therapy group. The two study groups had similar rates of renal events (hazard ratio in the revascularization group, 0.97; 95% CI, 0.67 to 1.40; P=0.88), major cardiovascular events (hazard ratio, 0.94; 95% CI, 0.75 to 1.19; P=0.61), and death (hazard ratio, 0.90; 95% CI, 0.69 to 1.18; P=0.46). Serious complications associated with revascularization occurred in 23 patients, including 2 deaths and 3 amputations of toes or limbs.
CONCLUSIONS: We found substantial risks but no evidence of a worthwhile clinical benefit from revascularization in patients with atherosclerotic renovascular disease. (Current Controlled Trials number, ISRCTN59586944.)

2009 Massachusetts Medical Society
PMID 19907042  N Engl J Med. 2009 Nov 12;361(20):1953-62. doi: 10.1056・・・
著者: Dharam J Kumbhani, Anthony A Bavry, James E Harvey, Russell de Souza, Roberto Scarpioni, Deepak L Bhatt, Samir R Kapadia
雑誌名: Am Heart J. 2011 Mar;161(3):622-630.e1. doi: 10.1016/j.ahj.2010.12.006.
Abstract/Text BACKGROUND: We sought to systematically evaluate whether percutaneous revascularization is associated with additional clinical benefit in patients with renal artery stenosis (RAS) as compared with medical management alone.
METHODS: We included randomized controlled trials that compared percutaneous revascularization in addition to medical therapy versus medical management alone in patients with RAS. Six trials with 1,208 patients were included.
RESULTS: At a mean follow-up of 29 months, there was no change in systolic blood pressure (weighted mean difference [WMD] = 1.20 mm Hg, 95% CI -1.18 to 3.58 mm Hg) or diastolic blood pressure (WMD = -1.60 mm Hg, 95% CI -4.22 to 1.02 mm Hg) from baseline in the percutaneous revascularization arm compared with the medical management arm. There was a reduction in the mean number of antihypertensive medications (WMD = -0.26, 95% CI -0.39 to -0.13, P < .001), but not serum creatinine (WMD = -0.14 mg/dL, 95% CI -0.29 to 0.007 mg/dL), in the percutaneous revascularization arm at the end of follow-up. Percutaneous revascularization was not associated with a significant difference in all-cause mortality (relative risk [RR] = 0.96, 95% CI 0.74-1.25), congestive heart failure (RR = 0.79, 95% CI 0.56-1.13), stroke (RR = 0.86, 95% CI 0.50-1.47), or worsening renal function (RR = 0.91, 95% CI 0.67-1.23) as compared with medical management.
CONCLUSIONS: In patients with RAS, percutaneous renal revascularization in addition to medical therapy may result in a lower requirement for antihypertensive medications, but not with improvements in serum creatinine or clinical outcomes, as compared with medical management over an intermediate period of follow-up. Further studies are needed to identify the appropriate patient population most likely to benefit from its use.

Copyright © 2011 Mosby, Inc. All rights reserved.
PMID 21392620  Am Heart J. 2011 Mar;161(3):622-630.e1. doi: 10.1016/j.・・・
著者: Christopher J Cooper, Timothy P Murphy, Donald E Cutlip, Kenneth Jamerson, William Henrich, Diane M Reid, David J Cohen, Alan H Matsumoto, Michael Steffes, Michael R Jaff, Martin R Prince, Eldrin F Lewis, Katherine R Tuttle, Joseph I Shapiro, John H Rundback, Joseph M Massaro, Ralph B D'Agostino, Lance D Dworkin, CORAL Investigators
雑誌名: N Engl J Med. 2014 Jan 2;370(1):13-22. doi: 10.1056/NEJMoa1310753. Epub 2013 Nov 18.
Abstract/Text BACKGROUND: Atherosclerotic renal-artery stenosis is a common problem in the elderly. Despite two randomized trials that did not show a benefit of renal-artery stenting with respect to kidney function, the usefulness of stenting for the prevention of major adverse renal and cardiovascular events is uncertain.
METHODS: We randomly assigned 947 participants who had atherosclerotic renal-artery stenosis and either systolic hypertension while taking two or more antihypertensive drugs or chronic kidney disease to medical therapy plus renal-artery stenting or medical therapy alone. Participants were followed for the occurrence of adverse cardiovascular and renal events (a composite end point of death from cardiovascular or renal causes, myocardial infarction, stroke, hospitalization for congestive heart failure, progressive renal insufficiency, or the need for renal-replacement therapy).
RESULTS: Over a median follow-up period of 43 months (interquartile range, 31 to 55), the rate of the primary composite end point did not differ significantly between participants who underwent stenting in addition to receiving medical therapy and those who received medical therapy alone (35.1% and 35.8%, respectively; hazard ratio with stenting, 0.94; 95% confidence interval [CI], 0.76 to 1.17; P=0.58). There were also no significant differences between the treatment groups in the rates of the individual components of the primary end point or in all-cause mortality. During follow-up, there was a consistent modest difference in systolic blood pressure favoring the stent group (-2.3 mm Hg; 95% CI, -4.4 to -0.2; P=0.03).
CONCLUSIONS: Renal-artery stenting did not confer a significant benefit with respect to the prevention of clinical events when added to comprehensive, multifactorial medical therapy in people with atherosclerotic renal-artery stenosis and hypertension or chronic kidney disease. (Funded by the National Heart, Lung and Blood Institute and others; ClinicalTrials.gov number, NCT00081731.).

PMID 24245566  N Engl J Med. 2014 Jan 2;370(1):13-22. doi: 10.1056/NEJ・・・

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