今日の臨床サポート

多発性嚢胞腎

著者: 河野春奈 順天堂大学大学院 医学研究科泌尿器外科学

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:2021/04/21
参考ガイドライン:
  1. 厚生労働科学研究費補助金難治性疾患等政策研究事業(難治性疾患政策研究事業)難治性腎障害に関する調査研究班編:エビデンスに基づく多発性嚢胞腎(PKD)診療ガイドライン2020
患者向け説明資料

概要・推奨   

  1. トルバプタンは、Cockcroft-Gault換算式でクレアチンクリアランス60mL/分以上、両腎容積750mL以上かつ腎容積増大速度がおおむね5%/年以上の多発性囊胞腎患者において腎容積の増加・腎機能低下の抑制効果が示されており、治療が推奨される(推奨度1)。
  1. 血圧をコントロールすることで腎機能障害の進行を予防できる。薬剤は可能な限りACE阻害薬/ARBを用いることが推奨される(推奨度2)。
  1. 30歳以上または家族歴がある場合に、脳動脈瘤のスクリーニングを行うことが推奨される(推奨度2)。
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:
河野春奈 : 未申告[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. エビデンスに基づく多発性嚢胞腎(PKD)診療ガイドライン 2020に基づき、主に診断の項とトルバプタンによる治療について改訂を行った。

病態・疫学・診察

疾患情報  
  1. 多発性嚢胞腎(Autosomal dominant polycystic kidney disease:ADPKD)は、最も多い遺伝性腎疾患で、常染色体優性遺伝形式で発症する。原因遺伝子であるPKD1またはPKD2の異常により起こり、両側の腎臓に多発する嚢胞を認める疾患である。
  1. 多くは家族歴がある。画像検査(超音波、CT、MRIなど)で両側の腎臓に多発する嚢胞を認め、診断は容易である。
  1. 診断時に家族歴を認めない場合が約1/4あるが、画像検査にて、16歳以上では両側の腎臓にそれぞれ5個以上、16歳未満ではそれぞれ3個以上の嚢胞を認めた場合確定診断となる。
  1. 鑑別診断には多発性単純性腎嚢胞、後天性嚢胞性腎疾患、結節性硬化症、常染色体劣性嚢胞腎などがある。
  1. 多発性嚢胞腎は国の定める指定難病であり、軽症で高額の医療費が3カ月以上持続する場合、または、重症の場合(①CKD重症度分類ヒートマップで赤部分、または②腎容積750mL以上かつ腎容積増大速度5%/年以上のうち、いずれかを満たした場合)などでは、申請し認定されると、多発性嚢胞腎について保険診療を受けた場合の自己負担が2割に軽減され、また、一定の自己負担額の上限以上の医療費について助成を受けることができる。(平成27年1月施行
  1. 難病法に基づく医療費助成制度
 
  1. 有効な治療法がない現時点では、小児ならびに若年者に対する診断を積極的に行う根拠は少ない。しかし、小児ならびに若年者で高血圧を認める場合もあること、小児で高血圧を発症している患者は正常血圧患者と比べて腎臓が有意に大きくなること、早期発症の重篤な例も少数認められることから、血圧測定や検尿を一般健康診断として行い、画像診断は家族から求められた場合に行う。したがって、ADPKDの家族では、高血圧の有無については学童期から注意することが推奨される(推奨度3J)。(参考文献:[1][2]
問診・診察のポイント  
  1. 遺伝形式は常染色体優性型であり、性別に関係なく遺伝する。家系に本疾患が存在せず、突然変異として新たに発症する場合(孤発例)が約5%である。

これより先の閲覧には個人契約のトライアルまたはお申込みが必要です。

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文献 

著者: Melissa A Cadnapaphornchai, Kim McFann, John D Strain, Amirali Masoumi, Robert W Schrier
雑誌名: Kidney Int. 2008 Nov;74(9):1192-6. doi: 10.1038/ki.2008.397. Epub 2008 Aug 20.
Abstract/Text Autosomal dominant polycystic kidney disease (ADPKD) is a common hereditary condition that may be diagnosed in utero. Our goal was to evaluate symptoms of ADPKD in children, including left ventricular mass index (LVMI), renal volume, renal function and microalbuminuria in relation to systolic and diastolic blood pressure. Eighty-five children were stratified by blood pressure into three cohorts: hypertensive (95th percentile and over), borderline hypertensive (75-95th percentile) and normotensive (75th percentile and below). There were no differences in gender, age, height, renal function, or microalbuminuria between the groups. Both the hypertensive and borderline hypertensive children had a significantly higher LVMI than normotensive children, with no significant difference between hypertensive and borderline hypertensive groups. There was a significant correlation between renal volume and both systolic and diastolic blood pressures in all subjects. Renal volume in hypertensive children was significantly larger than in the borderline hypertensive group, with no significant difference between normotensive and borderline hypertensive groups. These findings show that an increase in LVMI may be detected earlier than an increase in renal volume in children with ADPKD and borderline hypertension, suggesting that close monitoring of cardiac status is indicated in these children.

PMID 18716604  Kidney Int. 2008 Nov;74(9):1192-6. doi: 10.1038/ki.2008・・・
著者: Berenice Reed, Ehsan Nobakht, Sherry Dadgar, Mir Reza Bekheirnia, Amirali Masoumi, Frank Belibi, Xiang Dong Yan, Melissa Cadnapaphornchai, Robert W Schrier
雑誌名: Am J Kidney Dis. 2010 Jul;56(1):50-6. doi: 10.1053/j.ajkd.2010.02.349. Epub 2010 May 8.
Abstract/Text BACKGROUND: To date, there are no criteria for diagnosing autosomal dominant polycystic kidney disease (ADPKD) in at-risk children 15 years or younger.
STUDY DESIGN: Longitudinal (retrospective cohort study).
SETTING & PARTICIPANTS: 420 children (mean age, 8.3 +/- 4.2 years) with a family history of ADPKD were studied.
MEASUREMENTS: Renal ultrasonography was performed for cyst detection. Urine protein was measured using two 24-hour urine collections. Glomerular filtration rate was calculated using the Schwartz formula. Blood pressure measurements were performed in the arm with the highest blood pressure, using an appropriate cuff size. Standard 2-dimensional and Doppler echocardiography was performed for measuring left ventricular mass index.
PREDICTORS: None.
OUTCOME: Presence of renal cysts.
RESULTS: Renal cysts were detected in 193 children and no cysts were detected in 227 children. In children with renal cysts, 150 had bilateral and 43 had unilateral cysts. Children with bilateral cysts had larger kidneys and more hypertension than children with unilateral or no cysts. Follow-up in 77 children 15 years or younger showed bilateral cysts in 14 and unilateral cysts in 4 of the children who had no detectable renal cysts using ultrasonography at baseline. Similar follow-up of 26 children 15 years or younger with unilateral cysts detected at baseline showed bilateral cysts in 17 children using ultrasonography. By 15 years of age, 181 patients in the total group of 420 showed bilateral cysts. Overall, 193 of 304 children (63.4%) who had follow-up at any age developed bilateral cysts detected using ultrasonography.
LIMITATIONS: Follow-up unavailable for all participants.
CONCLUSION: The present results in 420 at-risk children with ADPKD 15 years or younger detected bilateral renal cysts using ultrasonography in 181 of the children who had a family history of this genetic disease.

PMID 20452711  Am J Kidney Dis. 2010 Jul;56(1):50-6. doi: 10.1053/j.aj・・・
著者: York Pei
雑誌名: Clin J Am Soc Nephrol. 2006 Sep;1(5):1108-14. doi: 10.2215/CJN.02190606. Epub 2006 Aug 9.
Abstract/Text Autosomal dominant polycystic kidney disease (ADPKD) is the most common Mendelian disorder of the kidney and affects all racial groups worldwide. It is characterized by focal development of renal and extrarenal cysts in an age-dependent manner. Typically, only a few renal cysts are detected in most affected individuals before 30 yr of age. However, by the fifth decade of life, hundreds to thousands of renal cysts will be found in the majority of patients. ADPKD is genetically heterogeneous. Mutations of two genes, PKD1 and PKD2, account for approximately 85 and 15% of cases, respectively. Although the clinical manifestations of these two genotypes overlap completely, patients with PKD1 have much more severe renal disease compared with those with PKD2, as evidenced by their ESRD occurring approximately 15 yr earlier. Renal ultrasonography commonly is used for the assessment of ADPKD, and age-dependent ultrasound diagnostic criteria with high sensitivity and specificity have been established for individuals who are born with 50% risk for PKD1. Although these diagnostic criteria are used widely for genetic counseling and for the evaluation of at-risk individuals as living-related kidney donors to their affected relatives, their application to individuals who are at risk for PKD2 or have undefined genotype needs to be refined further. Molecular genetic testing is available for ADPKD and may be useful for evaluation of at-risk individuals with equivocal imaging results, younger at-risk individuals as a living-related kidney donor, and individuals with atypical or de novo renal cystic disease.

PMID 17699332  Clin J Am Soc Nephrol. 2006 Sep;1(5):1108-14. doi: 10.2・・・
著者: D Ravine, R N Gibson, J Donlan, L J Sheffield
雑誌名: Am J Kidney Dis. 1993 Dec;22(6):803-7.
Abstract/Text This study documents the prevalence of simple renal cysts at various ages to produce a table of age-specific specificity values. The specificity of diagnosis for inherited renal cystic conditions depends primarily on the prevalence of simple renal cysts in disease-free subjects. To provide specificity data useful for the ultrasound assessment of individuals at genetic risk of having a renal cyst-forming condition, a prospective ultrasound study was performed. The urinary tract was examined in detail in 729 individuals referred for investigation of symptoms unrelated to the urinary tract and who had normal renal function. The prevalence of individuals with at least one renal cyst was 0% in those aged 15 to 29 years, 1.7% in those aged 30 to 49 years, 11.5% in those aged 50 to 70 years, and 22.1% in those aged 70 years and above. The prevalence of bilateral renal cysts (at least one cyst in each kidney) was 1% in those aged 30 to 49 years, 4% in those aged 50 to 70 years, and 9% in those aged 70 years and above. A table is provided that allows specificity estimates for differing diagnostic criteria together with 95% confidence limits for each estimate. In the younger age groups, bilateral renal cysts, particularly bilateral cysts with one or both kidneys having more than one cyst, are relatively uncommon. A reduced threshold for suspecting inherited renal cystic disease in younger individuals at high genetic risk will continue to have high specificity while improving the sensitivity of ultrasound diagnosis.

PMID 8250026  Am J Kidney Dis. 1993 Dec;22(6):803-7.
著者: K McHugh, D A Stringer, D Hebert, C A Babiak
雑誌名: Radiology. 1991 Feb;178(2):383-5. doi: 10.1148/radiology.178.2.1987597.
Abstract/Text To assess the sonographic frequency of simple renal cysts in children, the authors retrospectively reviewed the results of abdominal sonographic studies of 16,102 children performed over a 5-year period between January 1, 1985, and December 31, 1989. Patients with abnormal renal function, dysplastic kidneys, or a family history of polycystic kidney disease were excluded from the study. The authors' review of the sonograms revealed 37 simple cysts in 35 patients (0.22%); the cysts were evenly distributed by age and sex and measured from 0.3 to 7.0 cm in maximum diameter. Sixteen cysts (43%) were in the upper pole of the right kidney. Follow-up sonographic studies of 23 cysts in 22 patients for up to 5 years showed no change in size in 17 cysts (74%). The largest cyst was drained percutaneously; all other cysts were managed conservatively. No patient showed deterioration of renal function. Therefore, the authors concluded that in a pediatric patient demonstrating normal renal function, no further intervention is necessary when a simple renal cyst is identified at sonography.

PMID 1987597  Radiology. 1991 Feb;178(2):383-5. doi: 10.1148/radiolog・・・
著者: A B Nascimento, D G Mitchell, X M Zhang, T Kamishima, L Parker, G A Holland
雑誌名: Radiology. 2001 Dec;221(3):628-32. doi: 10.1148/radiol.2213010178.
Abstract/Text PURPOSE: To establish age-based standards for renal cysts depicted at magnetic resonance (MR) imaging and to compare these standards with existing standards for ultrasonography (US).
MATERIALS AND METHODS: Three radiologists reviewed subsecond T2-weighted single-shot fast spin-echo kidney MR imaging findings in 528 patients (248 men, 280 women) selected from consecutive abdominal MR studies without regard to clinical indication. Age, sex, and number and diameter of cysts were noted. Results were analyzed with nonparametric tests and were compared with published US results.
RESULTS: Men (mean, 2.0; 95% CI: 1.5, 2.5) had more renal cysts than women (mean, 1.2; 95% CI: 0.9, 1.5) (P < .001). Number and diameter of cysts increased with age (P < .001). Of 528 patients, 330 (62.5%) had at least one renal cyst, and 315 (59.7%) had cysts of 10 mm or less. MR imaging findings were comparable to published US criteria for type 1 autosomal dominant polycystic kidney disease (ADPKD) if only cysts larger than 1 cm were considered: Only one subject in the group of 18-29-year-old subjects had at least two renal cysts, and five of 493 subjects aged 30-59 years had at least two cysts in each kidney.
CONCLUSION: Compared with reported US results, MR imaging depicted an increased number of simple renal cysts in healthy individuals because of its increased sensitivity for cysts smaller than 1 cm. If only simple renal cysts larger than 1 cm are considered, US criteria for type 1 ADPKD can be applied to MR imaging.

PMID 11719656  Radiology. 2001 Dec;221(3):628-32. doi: 10.1148/radiol.・・・
著者: Jared J Grantham, Larry T Cook, Louis H Wetzel, Melissa A Cadnapaphornchai, Kyongtae T Bae
雑誌名: Clin J Am Soc Nephrol. 2010 May;5(5):889-96. doi: 10.2215/CJN.00550110. Epub 2010 Apr 1.
Abstract/Text BACKGROUND AND OBJECTIVES: In autosomal dominant polycystic kidney disease, cysts derived from tubules are detected at birth by ultrasound (threshold for detection >7.0 mm); thus, fetal cyst growth rates must exceed 2300%/yr. In adults, the combined renal cyst component enlarges at approximately 12%/yr by growth of individual cysts. To explore this discrepancy, the growth rates of individual cysts were determined in adult polycystic kidneys.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Diameter, volume, and growth rates of individual cysts were measured by magnetic resonance in 30 individual cysts in three adult patients over a span of 3 years. Results were confirmed in 22 cysts measured in five patients by computed tomography over a span of 11 years.
RESULTS: Mean cyst diameters were 20.4 +/- 9.9 mm (range 7.1 to 40.5 mm) at baseline and 25.8 +/- 15.6 mm (range 7.8 to 49.6 mm) after 3 years. Mean cyst volumes, determined by manual segmentation and summation of magnetic resonance cross sections, were 8.7 +/- 12.9 cm(3) (0.3 to 43.3 cm(3)) and 24.2 +/- 66.3 cm(3) (0.3 to 364.8 cm(3)) after 3 years. Mean cyst growth rates ranged from 6.9 to 23.9%/yr; the maximum growth rate was 71.1%/yr, far less than required to develop a 7-mm diameter cyst in utero. Results were similar in 22 cysts examined by computed tomography.
CONCLUSIONS: It was concluded that renal cysts detected by ultrasound in newborns must have grown at exuberant rates in utero; thereafter, expansion appears to proceed at much slower rates.

PMID 20360307  Clin J Am Soc Nephrol. 2010 May;5(5):889-96. doi: 10.22・・・
著者: Vicente E Torres, Peter C Harris
雑誌名: Kidney Int. 2009 Jul;76(2):149-68. doi: 10.1038/ki.2009.128. Epub 2009 May 20.
Abstract/Text Autosomal dominant polycystic kidney disease is the most prevalent, potentially lethal monogenic disorder. It has large inter- and intra-familial variability explained to a large extent by its genetic heterogeneity and modifier genes. An increased understanding of its underlying genetic, molecular, and cellular mechanisms and a better appreciation of its progression and systemic manifestations have laid out the foundation for the development of clinical trials and potentially effective therapies. The purpose of this review is to update the core of knowledge in this area with recent publications that have appeared during 2006-2009.

PMID 19455193  Kidney Int. 2009 Jul;76(2):149-68. doi: 10.1038/ki.2009・・・
著者: D Chauveau, Y Pirson, C Verellen-Dumoulin, A Macnicol, A Gonzalo, J P Grünfeld
雑誌名: Kidney Int. 1994 Apr;45(4):1140-6.
Abstract/Text Rupture of intracranial aneurysm (ICA) is a rare but severe manifestation of autosomal dominant polycystic kidney disease (ADPKD). In order to assess its natural history, to determine the prevalence of familial aggregation and to document linkage to PKD1 locus, we conducted a retrospective study on 77 ADPKD patients from 64 families presenting with ruptured (N = 71) or unruptured (N = 6) aneurysm. Information was collected on kidney disease, intracranial aneurysm and family history. Linkage to PKD1 locus was examined by five probes to obtain informative flanking markers. Within one year prior to rupture, blood pressure was normal in 29% of the patients. At the time of rupture, mean age was 39.5 years (range 15 to 69), renal function was normal in half of the patients and 11% were on renal replacement therapy. The ruptured aneurysm was usually located on the middle cerebral artery. Additional intact aneurysms (1 to 6) were detected in 31% of the patients. Surgical or endovascular treatment was performed in 54 (76%) patients whereas 17 (24%) had medical management only. Rupture of ICA was fatal in seven (10%) patients. On long-term follow-up 27 (38%) were left with severe disablement. Five patients bled from another aneurysm 2 days to 14 years after initial rupture. Only two of six patients with unruptured aneurysm alone were treated on a prophylactic basis. No clinical marker associated with aneurysm was found. A family history of aneurysm rupture was demonstrated in 10 (18%) kindreds. Linkage to the PKD1 locus was established in two of three tested families.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID 8007584  Kidney Int. 1994 Apr;45(4):1140-6.
著者: W I Schievink, V E Torres, D G Piepgras, D O Wiebers
雑誌名: J Am Soc Nephrol. 1992 Jul;3(1):88-95.
Abstract/Text The literature on the association of intracranial aneurysms in autosomal dominant polycystic kidney disease (ADPKD) consists mainly of case reports and small series of patients. To provide a more-detailed description of this association and its frequency, the records of all ADPKD patients with saccular intracranial aneurysms, all ADPKD autopsy cases including brain examination, and sex- and age-matched autopsy cases without ADPKD seen at the Mayo Clinic between 1950 and 1989 and of all Rochester residents with a diagnosis of subarachnoid hemorrhage or ADPKD between 1945 and 1984 were reviewed. The presentation of the 41 patients (22 men and 19 women; mean age, 46.4 yr) with this association was subarachnoid hemorrhage in 33, transient ischemic attacks in 2, incidental angiographic or autopsy finding in 5, and discovery during angiographic screening in 1. Thirty-one, seven, and three patients harbored one, two, and three aneurysms, respectively, arising from the middle cerebral artery (N = 23), anterior communicating artery (N = 16), internal carotid artery (N = 11), and vertebral or basilar artery (N = 4). A family history of intracranial aneurysm, subarachnoid hemorrhage, or intracranial hemorrhage at an early age was present in 22% of the patients. Small aneurysms (less than 5 mm) were less likely to have ruptured or caused symptoms (P less than 0.04). There was a trend for hypertension to be associated with the severity of the subarachnoid hemorrhage. Aneurysmal rupture occurred before age 50 in 64% of patients. Of the 89 ADPKD autopsy cases with brain examination, 22.5% had intracranial aneurysms.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID 1391712  J Am Soc Nephrol. 1992 Jul;3(1):88-95.
著者: Maria V Irazabal, John Huston, Vickie Kubly, Sandro Rossetti, Jamie L Sundsbak, Marie C Hogan, Peter C Harris, Robert D Brown, Vicente E Torres
雑誌名: Clin J Am Soc Nephrol. 2011 Jun;6(6):1274-85. doi: 10.2215/CJN.09731110. Epub 2011 May 5.
Abstract/Text BACKGROUND AND OBJECTIVES: Autosomal dominant polycystic kidney disease (ADPKD) patients have an increased risk for intracranial aneurysms (IAs). The importance of screening for unruptured IAs (UIAs) depends on their risks for growth and rupture.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: ADPKD patients with UIAs found by presymptomatic screening with magnetic resonance angiography (MRA) during 1989 to 2009 were followed initially at 6 months and annually, and less frequently after demonstration of stability.
RESULTS: Forty-five saccular aneurysms were detected in 38 patients from 36 families. Most were small (median diameter 3.5 mm) and in the anterior circulation (84%). Median age at diagnosis was 49 years. During cumulative imaging follow-up of 243 years, one de novo UIA was detected and increased in size from 2 to 4.4 mm over 144 months and two UIAs grew from 4.5 to 5.9 mm and 4.7 to 6.2 mm after 69 and 184 months, respectively. Seven patients did not have imaging follow-up. No change was detected in the remaining 28 patients. During cumulative clinical follow-up of 316 years, no aneurysm ruptured. Five patients died from unrelated causes and two were lost to follow-up after 8 and 120 months. Three patients underwent surgical clipping.
CONCLUSIONS: Most UIAs detected by presymptomatic screening in ADPKD patients are small and in the anterior circulation. Growth and rupture risks are not higher than those of UIAs in the general population. These data support very selective screening for UIAs in ADPKD patients, and widespread screening is not indicated.

PMID 21551026  Clin J Am Soc Nephrol. 2011 Jun;6(6):1274-85. doi: 10.2・・・
著者: H W Xu, Sheng Qiang Yu, Chang Lin Mei, Ming Hua Li
雑誌名: Stroke. 2011 Jan;42(1):204-6. doi: 10.1161/STROKEAHA.110.578740. Epub 2010 Dec 16.
Abstract/Text BACKGROUND AND PURPOSE: the association of autosomal-dominant polycystic kidney disease (ADPKD) with intracranial aneurysm (ICAN) is well known but little is known about the characteristics of ICAN in ADPKD. The purpose of this study was to investigate the prevalence and characteristics of ICAN in ADPKD.
METHODS: we screened 355 patients with ADPKD (mean age, 46.5 ± 13.2 years; range, 7 to 87 years) with 3-dimensional time-of-flight MR angiography. Size, location, and morphology of aneurysms were assessed. The prevalence and characteristics of ICAN in patients with ADPKD were evaluated. Patients with ICAN found by MR angiography and moderate renal function subsequently were recommended to undergo digital subtraction angiography for comparison.
RESULTS: the prevalence of ICAN in ADPKD was 12.4% (95% CI, 8.95% to 15.82%) with an equal gender distribution. The prevalence increased as age increased, reaching a peak value of 23.3% (95% CI, 16.85 to 29.75%) in the 60- to 69-year age group. The prevalence of ICAN in patients with ADPKD with a positive family history of hemorrhagic stroke or ICAN was higher than patients with ADPKD lacking such family history (relative risk, 1.968; 95% CI, 1.57 to 2.67). The mean diameter of ICAN was 3.85 ± 3.25 mm. The most frequent site of ICAN was the internal carotid artery. The result of digital subtraction angiography of 15 patients with 18 ICANs and moderate renal function corresponded to the detection of MR angiography.
CONCLUSIONS: the characteristics of ICAN in patients with ADPKD were different from some previous reports. Systematic screening of ICAN with 3-dimensional time-of-flight MR angiography is recommended for patients with ADPKD, particularly for adult patients (≧30 years) or patients with a positive family history of hemorrhagic stroke or ICAN.

PMID 21164130  Stroke. 2011 Jan;42(1):204-6. doi: 10.1161/STROKEAHA.11・・・
著者: Melissa A Cadnapaphornchai, Kim McFann, John D Strain, Amirali Masoumi, Robert W Schrier
雑誌名: Clin J Am Soc Nephrol. 2009 Apr;4(4):820-9. doi: 10.2215/CJN.02810608.
Abstract/Text BACKGROUND AND OBJECTIVES: Autosomal dominant polycystic kidney disease (ADPKD) is a progressive hereditary disorder affecting children and young adults. Early intervention may be necessary to significantly affect the long-term consequences of this disease.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The authors conducted a 5-yr randomized clinical trial to assess the effect of BP control with angiotensin-converting enzyme inhibition (ACEI) on disease progression in 85 children and young adults with ADPKD. Study groups were determined by subject BP, including hypertension (BP >or= 95th percentile), borderline hypertension (BP 75 to 95th percentile), and severe ADPKD (BP 10 renal cysts). The primary outcome variable was renal volume by ultrasound, with secondary outcome variables including left ventricular mass index (LVMI) and microalbuminuria. In secondary analysis, the authors compared results between hypertensive and normotensive groups.
RESULTS: The authors were not able to demonstrate a significant effect of ACEI on renal growth in young subjects with ADPKD. Hypertensive children were at particular risk for increases in renal volume and LVMI and decreased renal function as compared with the other study groups, and borderline hypertensive children were at high risk to develop hypertension over time. However, ACEI treatment was associated with stable renal function and LVMI in this group of children.
CONCLUSIONS: Close monitoring of cardiovascular and renal status is indicated in ADPKD children with hypertension or borderline hypertension. In contrast to effects in hypertensive ADPKD children, ACEI treatment in normotensive or borderline hypertensive ADPKD children may prevent the development of increased LVMI and deterioration in renal function.

PMID 19346430  Clin J Am Soc Nephrol. 2009 Apr;4(4):820-9. doi: 10.221・・・
著者: Robert W Schrier, Kimberly K McFann, Ann M Johnson
雑誌名: Kidney Int. 2003 Feb;63(2):678-85. doi: 10.1046/j.1523-1755.2003.00776.x.
Abstract/Text BACKGROUND: It is unknown whether the substantial increase in research, identification of risk factors for renal progression, greater antihypertensive armamentarium including inhibitors of the renin-angiotensin-aldosterone system (RAAS) and enhanced educational information have impacted the progression of autosomal dominant polycystic kidney disease (ADPKD) renal disease.
METHODS: An epidemiological study involving 513 ADPKD subjects was performed. The hypothesis tested was that over two separate periods, 1985 to 1992 versus 1992 to 2001, a significant slowing of renal function loss in ADPKD patients would be demonstrated in association with improved blood pressure (BP) control and inhibition of the RAAS as instituted by their primary care physicians.
RESULTS: ADPKD males and females in the later cohort (1992 to 2001) had longer mean and median survival times to ESRD than males and females in the earlier cohort (1985 to 1992). Analysis revealed that both males and females in the later cohort had significantly lower diastolic blood pressure (DBP) and mean arterial pressure (MAP) values than males and females in the earlier cohort. ADPKD male and female patients in the later cohort used significantly more angiotensin converting enzyme inhibitors (ACEIs) than ADPKD male and female patients in the earlier cohort.
CONCLUSIONS: These results demonstrate a significant slowing of ADPKD renal progression in both male and female patients that was associated with a significantly lower MAP and increased use of ACEIs in the later cohort (1992 to 2001) as compared to the early cohort (1985-1992).

PMID 12631134  Kidney Int. 2003 Feb;63(2):678-85. doi: 10.1046/j.1523-・・・
著者: Tazeen H Jafar, Paul C Stark, Christopher H Schmid, Svend Strandgaard, Anne-Lise Kamper, Giuseppe Maschio, Gavin Becker, Ronald D Perrone, Andrew S Levey, ACE Inhibition in Progressive Renal Disease (AIPRD) Study Group
雑誌名: Kidney Int. 2005 Jan;67(1):265-71. doi: 10.1111/j.1523-1755.2005.00077.x.
Abstract/Text BACKGROUND: It is not known whether angiotensin-converting-enzyme (ACE) inhibitors slow the progression of polycystic kidney disease (PKD). We performed a patient-level meta-analysis to compare the effect of antihypertensive regimens, including ACE inhibitors, to those without ACE inhibitors (controls) on kidney disease progression in patients with PKD.
METHODS: We analyzed a database of 11 randomized controlled trials including 1860 patients with nondiabetic kidney disease. We compared randomized groups for the decline in urine protein excretion and kidney disease progression (combined outcome of doubling of baseline serum creatinine or onset of kidney failure). We also performed multivariable linear regression and Cox proportional hazards analyses. Based on previous findings, we searched for interactions between the treatment effect (effect of ACE inhibitors vs. controls) and baseline urine protein excretion in both models.
RESULTS: Eight studies included a total of 142 subjects with PKD: 68 (48%) were randomized to ACE inhibitors and 74 (52%) were randomized to the control. Baseline mean (SD) urine protein excretion was 0.92 (1.40) g/day: 1.08 (1.50) g/day in the ACE inhibitor and 0.76 (1.28) g/day in the control group. During a mean follow-up of 2.3 years, mean (SD) urine protein excretion declined by 0.33 (1.11) g/day in the ACE inhibitor group and increased by 0.19 (0.88) g/day in the control group (P < 0.001). Kidney disease progression occurred in 50 patients: 20 patients (29%) in the ACE inhibitor group and 30 patients (41%) in the control group (P= 0.17). ACE inhibitors had a greater effect on lowering urine protein excretion and slowing kidney disease progression in patients with higher levels of baseline urine protein excretion (interaction P < 0.001 and P= 0.03, respectively).
CONCLUSION: As in other causes of non-diabetic kidney disease, antihypertensive regimens with ACE inhibitors are more effective in lowering urine protein excretion in patients with advanced PKD compared to regimens without ACE inhibitors, and this benefit is greater in patients with higher levels of baseline urine protein excretion. The effect of ACE inhibitors to slow kidney disease progression in PKD is inconclusive.

PMID 15610250  Kidney Int. 2005 Jan;67(1):265-71. doi: 10.1111/j.1523-・・・
著者: G Maschio, D Alberti, G Janin, F Locatelli, J F Mann, M Motolese, C Ponticelli, E Ritz, P Zucchelli
雑誌名: N Engl J Med. 1996 Apr 11;334(15):939-45. doi: 10.1056/NEJM199604113341502.
Abstract/Text BACKGROUND: Drugs that inhibit angiotensin-converting enzyme slow the progression of renal insufficiency in patients with diabetic neuropathy. Whether these drugs have a similar action in patients with other renal diseases is not known. We conducted a study to determine the effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of renal insufficiency in patients with various underlying renal diseases.
METHODS: In a three-year trial involving 583 patients with renal insufficiency caused by various disorders, 300 patients received benazepril and 283 received placebo. The underlying diseases included glomerulopathies (in 192 patients), interstitial nephritis (in 105), nephrosclerosis (in 97), polycystic kidney disease (in 64), diabetic nephropathy (in 21), and miscellaneous or unknown disorders (in 104). The severity of renal insufficiency was classified according to the base-line creatinine clearance: 227 patients had mild insufficiency (creatinine clearance, 46 TO 60 ml per minute), and 356 had moderate insufficiency (creatinine clearance, 30 to 45 ml per minute). The primary end point was a doubling of the base-line serum creatine concentration or the need for dialysis.
RESULTS: At three years. 31 patients in the benazepril group and 57 in the placebo group had reached the primary end point (P<0.001). In the benazepril group, the reduction in the risk of reaching the end point was 53 percent overall (95 percent confidence interval, 27 to 70 percent), 71 percent (95 percent confidence interval, 21 to 90 percent) among the patients with mild renal insufficiency, and 46 percent (95 percent confidence interval, 12 to 67 percent) among those with moderate renal insufficiency. The reduction in risk was greatest among the male patients; those with glomerular diseases, diabetic nephropathy, or miscellaneous or unknown causes of renal disease; and those with base-line urinary protein excretion above 1 g per 24 hours. Benazepril was not effective in patients with polycystic disease. Diastolic pressure decreased by 3.5 to 5.0 mm Hg in the benazepril group and increased by 0.2 to 1.5 mm Hg in the placebo group.
CONCLUSIONS: Benazepril provides protection against the progression of renal insufficiency in patients with various renal diseases.

PMID 8596594  N Engl J Med. 1996 Apr 11;334(15):939-45. doi: 10.1056/・・・
著者: Marjan A van Dijk, Martijn H Breuning, Rik Duiser, Leendert A van Es, Rudi G J Westendorp
雑誌名: Nephrol Dial Transplant. 2003 Nov;18(11):2314-20.
Abstract/Text BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors are capable of reducing proteinuria and microalbuminuria with preservation of renal function in diabetic and non-diabetic renal disease. We designed a study investigating the effect of enalapril on the protection of renal function in autosomal dominant polycystic kidney disease (ADPKD).
METHODS: We studied 61 normotensive and 28 hypertensive ADPKD patients. The normotensive group participated in a randomized double-blind placebo-controlled study, using enalapril. The hypertensive group was randomized for open label treatment with enalapril or the beta-blocker atenolol. The follow-up was 3 years, and renal function was established repetitively by measuring the clearance of inulin.
RESULTS: In the normotensive group, renal function at baseline was 112 +/- 3 ml/min and decreased by -8 +/- 2 ml/min (P < 0.001). The loss of renal function in the patients treated with enalapril or placebo was similar (-7 +/- 3 vs -9 +/- 1 ml/min; P = 0.4). Although blood pressure significantly decreased with enalapril treatment, it had no effect on microalbuminuria. In the hypertensive group, renal function at baseline was 89 +/- 2 ml/min. The mean decline in renal function was -12 +/- 2 ml/min (P < 0.001), and was equal in patients treated with enalapril and those treated with atenolol. The patients treated with atenolol required more additional treatment to control blood pressure, but no difference on microalbuminuria was observed between the two treatments.
CONCLUSION: This study was unable to detect a beneficial effect of ACE inhibition on loss of renal function in ADPKD patients.

PMID 14551359  Nephrol Dial Transplant. 2003 Nov;18(11):2314-20.
著者: T Ecder, A B Chapman, G M Brosnahan, C L Edelstein, A M Johnson, R W Schrier
雑誌名: Am J Kidney Dis. 2000 Mar;35(3):427-32.
Abstract/Text Hypertensive patients with autosomal dominant polycystic kidney disease (ADPKD) have a faster progression to end-stage renal disease (ESRD) than their normotensive counterparts. The aim of this prospective, randomized study is to compare the effects of the calcium channel blocker amlodipine and the angiotensin-converting enzyme inhibitor enalapril as first-line therapy on blood pressure, renal function, and urinary albumin excretion in hypertensive patients with ADPKD. Twenty-four patients with ADPKD with hypertension with creatinine clearances (Ccrs) greater than 50 mL/min/1.73 m(2) were included in the study. Twelve patients received amlodipine (mean dose, 9 mg/d), and 12 patients received enalapril (mean dose, 17 mg/d). The patients were followed up for 5 years. Baseline mean arterial pressures, which were 109 +/- 3 mm Hg in the amlodipine group and 108 +/- 3 mm Hg in the enalapril group, decreased significantly after 1 year of follow-up (amlodipine, 96 +/- 3 mm Hg; P < 0.005; enalapril, 89 +/- 2 mm Hg; P < 0.0005) and remained stable at year 5 (amlodipine, 97 +/- 3 mm Hg; P < 0.0005 versus baseline; enalapril, 94 +/- 3 mm Hg; P < 0.005 versus baseline). Ccrs, which were 83 +/- 5 mL/min/1.73 m(2) in the amlodipine group and 77 +/- 6 mL/min/1.73 m(2) in the enalapril group, remained stable after 1 year of follow-up and decreased significantly at year 3 in both groups (amlodipine, 67 +/- 5 mL/min/1.73 m(2); P < 0.01 versus year 1 and baseline; enalapril, 58 +/- 4 mL/min/1.73 m(2); P < 0.05 versus year 1 and P < 0.0005 versus baseline) with no significant change thereafter. No change was observed in urinary albumin-creatinine ratio in the amlodipine group (baseline, 68 +/- 21 mg/g; year 1, 52 +/- 21 mg/g; year 5, 148 +/- 74 mg/g), whereas it decreased significantly in the enalapril group at year 1 (baseline, 23 +/- 4 mg/g; year 1, 13 +/- 3 mg/g; P < 0.05) and remained stable until the end of the study at year 5 (14 +/- 6 mg/g). The investigators concluded that blood pressure was similar in both groups but only enalapril had a significant effect to sustain decreased urinary albumin excretion for a 5-year follow-up. Although proteinuria has been considered a surrogate of renal disease progression, further studies will be necessary to confirm this hypothesis in ADPKD, because after 5 years, no differences in renal function were observed between the enalapril and amlodipine groups. In comparison with patients with ADPKD with uncontrolled hypertension, effective control of blood pressure, as undertaken in the present study, should delay the onset of ESRD by approximately 15 years.

PMID 10692268  Am J Kidney Dis. 2000 Mar;35(3):427-32.
著者: Robert Schrier, Kimberly McFann, Ann Johnson, Arlene Chapman, Charles Edelstein, Godela Brosnahan, Tevfik Ecder, Lyn Tison
雑誌名: J Am Soc Nephrol. 2002 Jul;13(7):1733-9.
Abstract/Text This study sought to investigate the cardiac and renal effects of rigorous versus standard BP control on autosomal-dominant polycystic kidney disease (ADPKD). A prospective, randomized, 7-yr study was performed to examine the effect of rigorous (<120/80 mmHg) versus standard (135-140/85-90 mmHg) BP control on left ventricular mass index (LVMI) and kidney function in 75 hypertensive ADPKD patients with left ventricular hypertrophy. LVMI was measured by echocardiogram at baseline and at 1 and 7 yr. Renal function was assessed by measuring serum creatinine and 24-h creatinine clearance every 6 mo for 3 yr, then annually for an additional 4 yr. The baseline characteristics were comparable in the two groups. During the study, average mean arterial pressure was 90 +/- 5 mmHg for the rigorous group and 101 +/- 4 mmHg for the standard group (P < 0.0001). The LVMI decreased by 21% in the standard group and by 35% in the rigorous group. A mixed model longitudinal data analysis revealed that rigorous BP control was significantly more effective in decreasing LVMI (P < 0.01). There was no statistically significant difference in renal function between the two groups. In conclusion, left ventricular hypertrophy, a major cardiovascular risk factor, was decreased to a significantly greater extent by rigorous than standard BP control. This finding has particular clinical importance because cardiovascular complications are the most common cause of death in ADPKD patients.

PMID 12089368  J Am Soc Nephrol. 2002 Jul;13(7):1733-9.
著者: Y Kanno, H Suzuki, H Okada, T Takenaka, T Saruta
雑誌名: QJM. 1996 Jan;89(1):65-70.
Abstract/Text The effects of calcium channel blockers (CCBs) and angiotensin converting enzyme (ACE) inhibitors on blood pressure and the progression of renal dysfunction were compared in hypertensive patients with polycystic kidney disease (PKD). Twenty-six patients with PKD and hypertension who had been treated with other antihypertensive agents, such as diuretics, beta-blockers, or alpha-methyldopa, were followed up for two years, during which their blood pressure and renal function were monitored. Patients were divided into two groups classified according to the type of antihypertensive agents given. Group 1 (n = 14) received CCBs, while group 2 (n = 12) received ACE inhibitors. No significant differences were found in their blood pressure control and serum creatinine levels throughout the study. The creatinine clearances were decreased in both groups. However, the decreases in creatinine clearance were smaller (p < 0.05) in the group treated with CCBs. In addition, two patients in group 2 showed rapid increases in serum creatinine. Our data suggest that CCBs reduced blood pressure effectively and preserved renal function in PKD patients at least as well as ACE inhibitors.

PMID 8730344  QJM. 1996 Jan;89(1):65-70.
著者: Kikuo Nutahara, Eiji Higashihara, Shigeo Horie, Kouichi Kamura, Ken Tsuchiya, Toshio Mochizuki, Tatsuo Hosoya, Tomohiro Nakayama, Norio Yamamoto, Yoshio Higaki, Toshiko Shimizu
雑誌名: Nephron Clin Pract. 2005;99(1):c18-23. doi: 10.1159/000081790.
Abstract/Text BACKGROUND: Although hypertension is commonly found in patients with autosomal dominant polycystic kidney disease (ADPKD), there is no consensus about which antihypertensive agents are most appropriate. The effects of calcium channel blockers (CCB) and angiotensin II receptor blockers (ARB) on blood pressure and renoprotection were compared in hypertensive patients with ADPKD.
METHODS: We randomly assigned 49 participants to CCB amlodipine-based (2.5-10 mg/day) or ARB candesartan-based (2-8 mg/day) regimens. Twenty-five patients (13 males and 12 females) received amlodipine, and 24 patients (13 males and 11 females) received candesartan. This was followed up for 36 months.
RESULTS: Baseline characteristics were similar, and blood pressure was well controlled in both groups throughout the study period. Six out of 25 (24.0%) amlodipine and 1 out of 24 (4.2%) candesartan patients were terminated from the protocol due to a twofold increase in serum creatinine and/or decrease in creatinine clearance (Ccr) to half of the baseline. The renal event-free survival rate was significant (p < 0.05, Breslow-Gehan-Wilcoxon test). Serum creatinine was higher in the amlodipine group than in the candesartan group at 24 and 36 months (p < 0.05). The decrease in Ccr at 36 months was larger in the amlodipine group than in the candesartan group (DeltaCcr: -20.9 +/- 13.1 vs. -4.8 +/- 13.8 ml/min, p < 0.01). Urinary protein excretion was significantly lower in the candesartan group than in the amlodipine group at 36 months. Urinary albumin excretion was significantly lower in the candesartan group than in the amlodipine group at 12, 24 and 36 months.
CONCLUSIONS: The renoprotective effect of candesartan is considered more favorable than amlodipine in the treatment of ADPKD. This is independent of the antihypertensive effect per se.

Copyright (c) 2005 S. Karger AG, Basel.
PMID 15637459  Nephron Clin Pract. 2005;99(1):c18-23. doi: 10.1159/000・・・
著者: Michihiro Mitobe, Takumi Yoshida, Hidekazu Sugiura, Shunji Shiohira, Katsunori Shimada, Kosaku Nitta, Ken Tsuchiya
雑誌名: Clin Exp Nephrol. 2010 Dec;14(6):573-7. doi: 10.1007/s10157-010-0329-5. Epub 2010 Aug 11.
Abstract/Text BACKGROUND: In the tubular cells of patients with polycystic kidney disease (PKD), a reduced intracellular Ca(2+) level accelerates cell proliferation, resulting in cyst formation. Thus, whether calcium channel blockers (CCB) are useful for the treatment of hypertension in patients with PKD is questionable.
METHODS: Thirty-two outpatients with autosomal dominant PKD (ADPKD) were treated at Tokyo Women's Medical University between 2003 and 2008; these patients were studied retrospectively. Periods during which the antihypertensive drug prescriptions for CCB and/or renin-angiotensin-aldosterone system inhibitors (RAAS-I; including angiotensin converting enzyme inhibitor and angiotensin II receptor blocker) had not been changed for at least 1 year and during which time a diuretic agent had not been prescribed were selected from among the clinical histories of the 32 outpatients. Consequently, 31 periods of 31 patients were analyzed, and mean treatment duration was 2.4 years in this study. The estimated glomerular filtration rate (eGFR) was used to evaluate renal function. To evaluate the influence of CCB and RAAS-I with respect to the decrease of the eGFR, analysis of covariance (ANCOVA), including confounding factors [baseline eGFR, mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP)], was used. Only CCB significantly contributed to a reduction in ∆eGFR in both a univariable ANCOVA and a multivariable ANCOVA. None of the confounding factors, RAAS-I, the baseline eGFR, or blood pressure, contributed to reductions in ∆eGFR.
CONCLUSION: These results suggest that from a renoprotective perspective, CCB should possibly be avoided in patients with PKD unless treatment for resistant hypertension is necessary.

PMID 20700620  Clin Exp Nephrol. 2010 Dec;14(6):573-7. doi: 10.1007/s1・・・
著者: Connie J Wang, Catherine Creed, Franz T Winklhofer, Jared J Grantham
雑誌名: Clin J Am Soc Nephrol. 2011 Jan;6(1):192-7. doi: 10.2215/CJN.03950510. Epub 2010 Sep 28.
Abstract/Text BACKGROUND AND OBJECTIVES: In animal models of polycystic kidney disease, the ingestion of large amounts of water promotes diuresis by suppressing plasma levels of arginine vasopressin (AVP) and renal levels of cAMP, slowing cyst progression. Whether simple water ingestion is a potential therapeutic strategy for individuals with autosomal dominant polycystic kidney disease (ADPKD) is unknown. In this study, a simple method to quantify the amount of water to achieve a specific mean urine osmolality target in patients with ADPKD was developed and tested.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In eight ADPKD patients eating typical diets, osmolality and volume were measured in 24-hour urine collections. The amount of additional ingested water required daily to achieve a mean urine osmolality of 285 ± 45 mosm/kg was determined. Participants were instructed to distribute the prescribed water over waking hours for each of 5 days. Blood chemistries, 24-hour urine collections, BP, and weight were measured before and after the period of supplemental water intake.
RESULTS: Five patients achieved the 285 mosm/kg urine target without difficulty. Mean urine osmolality decreased and mean urine volume increased; serum sodium, weight, and BP were unchanged. Daily osmolar excretion remained constant, indicating a stable ad lib dietary intake of solutes and protein over the 2-week study period.
CONCLUSIONS: The amount of additional water needed to achieve a urine osmolality target can be approximated from the urine osmolar excretion in ADPKD patients eating typical diets, providing a quantitative method to prescribe supplemental water for such individuals.

PMID 20876670  Clin J Am Soc Nephrol. 2011 Jan;6(1):192-7. doi: 10.221・・・
著者: Shizuko Nagao, Kazuhiro Nishii, Makoto Katsuyama, Hiroki Kurahashi, Tohru Marunouchi, Hisahide Takahashi, Darren P Wallace
雑誌名: J Am Soc Nephrol. 2006 Aug;17(8):2220-7. doi: 10.1681/ASN.2006030251. Epub 2006 Jun 28.
Abstract/Text Renal enlargement in polycystic kidney disease (PKD) is caused by the proliferation of mural epithelial cells and transepithelial fluid secretion into the cavities of innumerable cysts. Arginine vasopressin (AVP) stimulates the proliferation of human PKD cells in vitro via cAMP-dependent activation of the B-Raf/MEK (MAPK/ERK kinase/extracellular signal-regulated kinase (ERK) pathway. ERK activity is elevated in cells that line the cysts in animals with PKD, and AVP receptor antagonists reduce ERK activity and halt disease progression. For suppression of the effect of AVP physiologically, water intake was increased in PCK rats, a model of PKD, and the effect on renal morphology, cellular mechanism, and function was determined. The addition of 5% glucose in the drinking water increased fluid intake approximately 3.5-fold compared with rats that received tap water. In PCK rats, increased water intake for 10 wk reduced urinary AVP excretion (68.3%), and urine osmolality fell below 290 mOsmol/kg. High water intake was associated with reduced renal expression of AVP V2 receptors (41.0%), B-Raf (15.4%), phosphorylated ERK (38.1%), and proliferating cell nuclear antigen-positive renal cells (61.7%). High water intake reduced the kidney/body weight ratio 28.0% and improved renal function. Taken together, these data demonstrate that water intake that is sufficient to cause persistent water diuresis suppresses B-Raf/MEK/ERK activity and decreases cyst and renal volumes in PCK rats. It is suggested that limiting serum AVP levels by increased water intake may be beneficial to some patients with PKD.

PMID 16807403  J Am Soc Nephrol. 2006 Aug;17(8):2220-7. doi: 10.1681/A・・・
著者: F Locatelli, D Alberti, G Graziani, G Buccianti, B Redaelli, A Giangrande
雑誌名: Lancet. 1991 Jun 1;337(8753):1299-304.
Abstract/Text A multicentre, prospective trial was organised to clarify the role of protein restriction in the progression of chronic renal insufficiency (CRI). 456 adult patients were assigned either a low-protein diet (0.6 g/kg body weight daily; n = 226) or a "normal" controlled-protein diet (1.0 g/kg daily; n = 230) and were stratified into three groups (A-C) with increasing baseline plasma creatinine concentrations. Each patient was followed up for 2 years or until an endpoint (a doubling of the baseline plasma creatinine or a need for dialysis) was reached. The difference between the diet groups in cumulative renal survival defined by these endpoints (27 low-protein, 42 controlled-protein) was of borderline significance (p less than 0.06). The difference in renal survival between the low-protein and controlled-protein diet groups was of borderline significance in group A (0 vs 4 endpoints), significant in group B (10 vs 21 endpoints; p less than 0.025), and not significant in group C. There were no differences among the diet groups or subgroups in mean plasma creatinine concentrations, creatinine clearance, the slope of the plasma creatinine reciprocal, or mean blood pressures. Compliance was good in the controlled-protein group but poor for the low-protein diet: the difference in protein intake between the groups was substantially less than that required by the protocol. However, there was no correlation between the progression of renal failure and protein catabolic rate. These findings offer little, if any, support to the hypothesis that protein restriction retards CRI progression: careful medical care and a "normal" controlled protein intake also allow very slow progression of CRI.

PMID 1674294  Lancet. 1991 Jun 1;337(8753):1299-304.
著者: G Choukroun, Y Itakura, G Albouze, J L Christophe, N K Man, J P Grünfeld, P Jungers
雑誌名: J Am Soc Nephrol. 1995 Dec;6(6):1634-42.
Abstract/Text Autosomal dominant polycystic kidney disease (ADPKD) frequently leads to end-stage renal failure (ESRF) in the sixth decade of life, but considerable heterogeneity exists in the rate of progression of renal failure. The respective contribution of genetic factors and of potentially amendable factors, such as blood pressure control or protein intake limitation, on the rate of progression in ADPKD patients is still debated. To evaluate the role of factors influencing the rate of progression of renal failure in ADPKD, we retrospectively analyzed the annual rate of decline of creatinine clearance (Ccr) in 109 ADPKD patients followed from the time a Ccr value of 30 to 50 mL per min/1.73 m2 was measured until ESRD and need for hemodialysis (Study A), and in 48 undialyzed ADPKD patients followed for at least 4 yr from the time a Ccr value of 50 to 60 mL per min/1.73 m2 was measured (Study B). In Study A, the decline in Ccr (delta Ccr) (mean +/- SE) was 5.8 +/- 0.2 mL per min/1.73 m2 per year in the whole series, and was lower in females than in males (5.0 +/- 0.2 versus 6.4 +/- 0.2, P < 0.001). Accordingly, ESRF was reached at a later age in female patients (55.1 +/- 1.2 versus 50.6 +/- 1.2 yr, P < 0.01). The age at ESRF in male patients was lower when the disease was transmitted by mother than by father (46.3 +/- 1.9 versus 54.1 +/- 1.8 yr, P < 0.01), whereas no significant effect of the gender of the affected parent was apparent in female patients. By regression analysis, there was a positive but weak relationship between delta Ccr and mean arterial pressure (average value during follow-up, 107 +/- 1 mm Hg, r = 0.224, P < 0.05) but not with dietary protein intake (mean value in follow-up, 0.87 +/- 0.03 g/kg per day, r = 0.10, P = 0.33) nor with proteinuria at baseline, which was lower than 0.3 g/day in 104 cases (r = 0.10, P = 0.28). There was a negative relationship between age at ESRF and delta Ccr (r = 0.245, P < 0.05), with a later and slower progression in older subjects. In Study B, the mean decline in renal function during follow-up was 5.3 +/- 0.4 mL/min/1.73 m2 per year, a value close to that observed in Study A. By multiple regression analysis of the overall population (studies A and B combined), only MAP, age and gender were independent predictive factors of delta Ccr but all studied parameters taken together accounted for at best 20% of delta Ccr variation. We conclude that the rate of progression of renal failure in ADPKD patients is mainly determined by gene expression, with female gender and older age associated with a slower progression, whereas blood pressure control, but not protein intake, exerts a limited beneficial influence on the rate of progression in patients with advanced polycystic kidney disease who already have significant renal insufficiency.

PMID 8749691  J Am Soc Nephrol. 1995 Dec;6(6):1634-42.
著者: S Klahr, J A Breyer, G J Beck, V W Dennis, J A Hartman, D Roth, T I Steinman, S R Wang, M E Yamamoto
雑誌名: J Am Soc Nephrol. 1995 Jun;5(12):2037-47.
Abstract/Text In the Modification of Diet in Renal Disease Study, a follow-up (mean, 2.2 yr) of 200 study participants with autosomal dominant polycystic kidney disease (ADPKD) was conducted to determine the effect of lowering protein intake and blood pressure on the rate of decline in GFR. The rate of decline was faster in participants with ADPKD than in persons with other diagnoses, reflecting, in part, faster disease progression in the ADPKD group. Baseline characteristics that predicted a faster rate of decline in GFR in persons with ADPKD were greater serum creatinine (independent of GFR), greater urinary protein excretion, higher mean arterial pressure (MAP), and younger age. In patients with initial GFR values between 25 and 55 mL/min per 1.73 m2, neither assignment to a low-protein diet group nor assignment to a low blood pressure group significantly reduced the rate of decline of GFR in ADPKD participants. Similarly, the decline in GFR was not related to achieved protein intake or MAP. In participants with GFR values between 13 and 24 mL/min per 1.73 m2, assignment to the low MAP group led to a somewhat more rapid decline in GFR. However, the more rapid decline in GFR did not appear to be due to a detrimental effect of low blood pressure or the antihypertensive agents used to reach the low blood pressure goal. Lower protein intake, but not prescription of the keto acid-amino acid supplement, was marginally associated with a slower progression of renal disease.

PMID 7579052  J Am Soc Nephrol. 1995 Jun;5(12):2037-47.
著者: Antoine Jacquet, Nicolas Pallet, Michèle Kessler, Maryvonne Hourmant, Valérie Garrigue, Lionel Rostaing, Henri Kreis, Christophe Legendre, Marie-France Mamzer-Bruneel
雑誌名: Transpl Int. 2011 Jun;24(6):582-7. doi: 10.1111/j.1432-2277.2011.01237.x. Epub 2011 Feb 26.
Abstract/Text Renal transplantation in patients with autosomal dominant polycystic kidney disease (ADPKD) is a medical and surgical challenge. Detailed longitudinal epidemiological studies on large populations are lacking and it is mandatory to care better for these patients. The success of such a project requires the development of a validated epidemiological database. Herein, we present the results of the largest longitudinal study to date on renal transplant in patients with ADPKD. The 15-year outcomes following renal transplantation of 534 ADPKD patients were compared with 4779 non-ADPKD patients. This comprehensive, longitudinal, multicenter French study was performed using the validated database, DIVAT (Données Informatisées et VAlidées en Transplantaion). We demonstrate that renal transplantation in ADPKD is associated with better graft survival, more thromboembolic complications, more metabolic complications, and increased incidence of hypertension, whereas the prevalence of infections is not increased. This study provides important new insights that could lead to a better care for renal transplant patients with ADPKD.

© 2011 The Authors. Transplant International © 2011 European Society for Organ Transplantation.
PMID 21352383  Transpl Int. 2011 Jun;24(6):582-7. doi: 10.1111/j.1432-・・・
著者: Melissa Millar, Youssef S Tanagho, Mohammed Haseebuddin, Ralph V Clayman, Sam B Bhayani, R Sherburne Figenshau
雑誌名: J Endourol. 2013 May;27(5):528-34. doi: 10.1089/end.2012.0529. Epub 2013 Feb 5.
Abstract/Text PURPOSE: To provide a summary of the relevant literature regarding the impact of surgical cyst decortication on hypertension, renal function, and pain management in patients with autosomal dominant polycystic kidney disease (ADPKD).
METHODS: Data collection was conducted via a Medline search using the subject headings autosomal dominant polycystic kidney disease, surgery, decortication, and marsupialization. Additional reports were derived from references included within these articles.
RESULTS: Despite a trend for improved blood pressure control after cyst decortication in some studies, this cumulative review of the literature did not provide consistent evidence supporting the role of this procedure in blood pressure management in patients with ADPKD. Surgical cyst decortication was associated with renal deterioration in a subset of patients with compromised baseline renal function but did not otherwise appear to have a significant impact on renal function in the majority of studies reviewed. Improvement in chronic pain after this procedure was ubiquitously reported across all studies examined.
CONCLUSIONS: Despite a potential role in blood pressure management in the setting of ADPKD, surgical cyst decortication has not been definitively shown to alleviate hypertension in this clinical setting. Renal function does not appear to improve following this surgery. Patients with compromised baseline renal function appear to be at increased risk for further deterioration in renal function after cyst decortication, although the role of this procedure in altering the natural trajectory of renal failure in this patient subset needs further investigation. Cyst decortication is highly effective in the management of disease-related chronic pain for the majority of patients with ADPKD, providing durable pain relief in this patient population.

PMID 23157176  J Endourol. 2013 May;27(5):528-34. doi: 10.1089/end.201・・・
著者: S J Schwab, S J Bander, S Klahr
雑誌名: Am J Med. 1987 Apr;82(4):714-8.
Abstract/Text Upper urinary tract (renal) infections have been reported to be frequent and difficult to treat in patients with autosomal dominant polycystic kidney disease. This study examined renal infections and responses to therapy in this patient population. Fifteen cyst infections and 11 parenchymal infections occurred during the study. Eighty-seven percent of the cyst and 91 percent of the parenchymal infections occurred in women. Gram-negative enterics were the causative organisms in 92 percent of the cyst and 100 percent of the parenchymal infections. All of the parenchymal but only one of the cyst infections responded to therapy with ampicillin and an aminoglycoside despite favorable sensitivities. Eighty-three percent of the cyst infections were eradicated with use of lipid-soluble antibiotics. It is concluded that Cyst infections are refractory to therapy with the antibiotics commonly used to treat urinary infections; Female preference and enteric organism predominance suggest that these renal infections are acquired retrograde from the urinary bladder.

PMID 3565428  Am J Med. 1987 Apr;82(4):714-8.
著者: Marie C Hogan, Suzanne M Norby
雑誌名: Adv Chronic Kidney Dis. 2010 May;17(3):e1-e16. doi: 10.1053/j.ackd.2010.01.005.
Abstract/Text Transient episodes of pain are common in autosomal dominant polycystic kidney disease (ADPKD). A small fraction of patients have disabling chronic pain. In this review, we discuss the etiologies of pain in ADPKD; review how ADPKD patients should be assessed; and discuss medical, surgical, and other management options.

Copyright 2010 National Kidney Foundation, Inc. All rights reserved.
PMID 20439087  Adv Chronic Kidney Dis. 2010 May;17(3):e1-e16. doi: 10.・・・
著者: J D Harley, F H Shen, S J Carter
雑誌名: AJR Am J Roentgenol. 1980 Apr;134(4):818-20. doi: 10.2214/ajr.134.4.818.
Abstract/Text
PMID 6767371  AJR Am J Roentgenol. 1980 Apr;134(4):818-20. doi: 10.22・・・
著者: S T Hahn, S H Park, J M Lee, C Y Kim, Y S Chang
雑誌名: Cardiovasc Intervent Radiol. 1999 Sep-Oct;22(5):422-4.
Abstract/Text A 65-year-old man with adult polycystic kidney disease (APKD) and chronic renal failure suffered from intractable abdominal pain and distension for 2 weeks. Meperidine infusion did not alleviate his pain. However, pain and abdominal distension were successfully controlled by embolization of both renal arteries.

PMID 10501897  Cardiovasc Intervent Radiol. 1999 Sep-Oct;22(5):422-4.
著者: Y Ubara, H Katori, T Tagami, S Tanaka, M Yokota, Y Matsushita, F Takemoto, T Imai, S Inoue, K Kuzuhara, S Hara, A Yamada
雑誌名: Am J Kidney Dis. 1999 Nov;34(5):926-31. doi: 10.1016/S0272-6386(99)70052-1.
Abstract/Text We report a patient with autosomal dominant polycystic kidney disease (ADPKD) undergoing long-term hemodialysis who underwent transcatheter arterial embolization (TAE) of the renal arteries to shrink enlarged kidneys. In 1983, the patient started hemodialysis because of chronic renal failure secondary to ADPKD. However, renal size continued to increase. In January 1997, he was admitted to our hospital with abdominal distension and anorexia, in addition to progression of anemia. Upper gastroendoscopy showed an esophageal ulcer and severe external compression of the stomach. Renal angiography using the Seldinger technique showed stretched and deformed segmental renal arteries with massive enlargement of the kidneys. TAE with stainless steel coils was performed on both renal arteries. With a rapid and progressive decrease in kidney size, anorexia and anemia were improved, and the gastrointestinal compression was eliminated. In some patients with ADPKD, renal size continues to increase even after the initiation of dialysis. In about 10 years, patients develop gastrointestinal complications, such as dysphagia, ileus, severe constipation, and intestinal perforation. Surgical procedures such as nephrectomy are not satisfactory. This report shows that TAE is a safe and effective therapy for patients with ADPKD with massively enlarged kidneys.

PMID 10561151  Am J Kidney Dis. 1999 Nov;34(5):926-31. doi: 10.1016/S0・・・
著者: Yoshifumi Ubara, Tetsuo Tagami, Naoki Sawa, Hideyuki Katori, Masafumi Yokota, Fumi Takemoto, Sumio Inoue, Keihachirou Kuzuhara, Shigeko Hara, Akira Yamada
雑誌名: Am J Kidney Dis. 2002 Mar;39(3):571-9. doi: 10.1053/ajkd.2002.31407.
Abstract/Text Kidneys of patients with autosomal dominant polycystic kidney disease (ADPKD) usually continue to increase in size, even after patients begin dialysis therapy, and the mass effects may lead to severe complications. Such external conventional therapies as surgical and laparoscopic procedures have not yielded satisfactory results. Because kidneys in patients with ADPKD usually are supplied by well-developed arteries, we attempted renal contraction therapy in patients with ADPKD by renal transcatheter arterial embolization (TAE) using intravascular coils. After obtaining informed consent, we selected anuric patients on dialysis therapy with markedly distended abdomens or macroscopic hematuria. Between October 1996 and December 2000, a total of 64 patients were treated. Renal size, abdominal circumference, dry weight, hematocrit, and insulin-like growth factor-I were measured before TAE and 3, 6, and 12 months after TAE. Renal sizes decreased to 73.8% +/- 12.0%, 61.7% +/- 14.7%, and 53.4% +/- 11.6% of preinterventional values at 3, 6, and 12 months after therapy, respectively (P < 0.0001). Abdominal circumference and dry weight were significantly decreased at 3, 6, and 12 months (P < 0.0001) compared with baseline values before therapy. Hematocrits increased sequentially after 3, 6, and 12 months (P < 0.0001). Levels of insulin-like growth factor-I an index of nutritional status, significantly increased at 3, 6, and 12 months compared with the baseline value (P < 0.001). This therapy was effective for all patients. Serious complications were not seen after this treatment, although such minor complications as fever and flank pain were observed within the first week after the procedure. Our internal treatment with TAE is a safe and effective procedure that has resulted in improvement in the quality of life and nutritional status of patients with ADPKD.

Copyright 2002 by the National Kidney Foundation, Inc.
PMID 11877576  Am J Kidney Dis. 2002 Mar;39(3):571-9. doi: 10.1053/ajk・・・
著者: Yusuke Sakuhara, Fumi Kato, Daisuke Abo, Yu Hasegawa, Tadashi Shimizu, Satoshi Terae, Hiroki Shirato
雑誌名: J Vasc Interv Radiol. 2008 Feb;19(2 Pt 1):267-71. doi: 10.1016/j.jvir.2007.10.007.
Abstract/Text Kidney enlargement in autosomal-dominant polycystic kidney disease (ADPKD) may cause symptoms by compressing the alimentary tract, lungs, and heart. The clinical symptoms may be progressive, may markedly decrease quality of life, and may even be life-threatening. Although treatment of this disease is often difficult, transcatheter arterial embolization (TAE) with metallic coils has been reported as a renal contraction therapy that is less invasive than surgery. The present report describes a case of ADPKD successfully treated by TAE with absolute ethanol after a previous TAE procedure with metallic coils failed to contract the affected kidneys because of recanalization.

PMID 18341960  J Vasc Interv Radiol. 2008 Feb;19(2 Pt 1):267-71. doi: ・・・
著者: Hark Rim, Gyoo-Sik Jung, Yeon Soon Jung
雑誌名: Korean J Radiol. 2010 Sep-Oct;11(5):574-8. doi: 10.3348/kjr.2010.11.5.574. Epub 2010 Aug 27.
Abstract/Text The mass effect of nephromegaly in patients with autosomal dominant polycystic kidney disease may cause pain and symptoms by compressing the alimentary tract, lungs, and heart. Conventional therapies exist to contract enlarged polycystic kidneys including surgical and interventional procedures. A surgical nephrectomy is often difficult to perform in dialysis patients due to the associated risks related to surgery. In contrast, renal transcatheter arterial embolization (TAE) with metallic coils, which is a less invasive interventional procedure, can also be utilized to contract enlarged kidneys in dialysis patients as an effective treatment. However, metallic coils present the possibility of recanalization and cost issues. Thus, we used ethanol instead of coils in renal TAE to resolve these issues. We report a dialysis patient with enlarged polycystic kidneys and poor oral intake due to abdominal distention that was successfully treated by TAE with absolute ethanol.

PMID 20808704  Korean J Radiol. 2010 Sep-Oct;11(5):574-8. doi: 10.3348・・・
著者: Hiroyuki Morishita, Takuji Yamagami, Yoshito Takeuchi, Tomohiro Matsumoto, Shunsuke Asai, Tsuneyuki Nakanouchi, Osamu Sato, Tsunehiko Nishimura
雑誌名: J Vasc Interv Radiol. 2011 Nov;22(11):1631-3. doi: 10.1016/j.jvir.2011.07.003.
Abstract/Text
PMID 22024120  J Vasc Interv Radiol. 2011 Nov;22(11):1631-3. doi: 10.1・・・
著者: Takashi Mukai, Hidefumi Mimura, Hideo Gobara, Mitsuharu Shimizu, Harutaka Niiya, Susumu Kanazawa
雑誌名: Acta Med Okayama. 2011 Oct;65(5):347-51.
Abstract/Text We report herein the case of a 76-year-old woman with autosomal dominant polycystic kidney disease (ADPKD) and chronic renal failure resulting in intractable abdominal distension and anorexia. Computed tomography (CT) showed enlarged and cystic kidneys. We performed transcatheter arterial embolization (TAE) for renal arteries with ethanol. Absolute ethanol with iodinated contrast medium or Lipiodol was delivered into both renal arteries. The patient's low-grade fever subsided in 5 days, and no other complication occurred. The sensation of abdominal distension diminished approximately 1 month after embolization. A progressive decrease in kidney size was observed soon after embolization. The percentage of the decrement of kidney size was approximately 50% after 17 months. These results indicate that renal TAE with ethanol is a safe, cost-effective, and minimally invasive technique to reduce kidney size in symptomatic ADPKD patients.

PMID 22037273  Acta Med Okayama. 2011 Oct;65(5):347-51.
著者: G J Rinkel, M Djibuti, A Algra, J van Gijn
雑誌名: Stroke. 1998 Jan;29(1):251-6.
Abstract/Text BACKGROUND AND PURPOSE: The estimates on the prevalence and the risk of rupture of intracranial saccular aneurysms vary widely between studies. We conducted a systematic review on prevalence and risk of rupture of intracranial aneurysms and classified the data according to study design, study population, and aneurysm characteristics.
METHODS: We searched for studies published between 1955 and 1996 by means of a MEDLINE search and a cumulative review of the reference lists of all relevant publications. Two authors independently assessed eligibility of all studies and extracted data on study design and on numbers and characteristics of patients and aneurysms.
RESULTS: For data on prevalence we found 23 studies, totalling 56,304 patients; 6685 (12%) of these patients were from 15 angiography studies. Prevalence was 0.4% (95% confidence interval, 0.4% to 0.5%) in retrospective autopsy studies, 3.6% (3.1 to 4.1) for prospective autopsy studies, 3.7% (3.0 to 4.4) in retrospective angiography studies, and 6.0% (5.3 to 6.8) in prospective angiography studies. For adults without specific risk factors, the prevalence was 2.3% (1.7 to 3.1); it tended to increase with age. The prevalence was higher in patients with autosomal dominant polycystic kidney disease (relative risk [RR], 4.4 [2.7 to 7.2]), a familial predisposition (RR, 4.0 [2.7 to 6.0]), or atherosclerosis (RR, 2.3 [1.7 to 3.1]). Only 8% (5 to 11) of the aneurysms were >10 mm. For the risk of rupture, we found nine studies, totalling 3907 patient-years. The overall risk per year was 1.9% (1.5 to 2.4); for aneurysms = 10 mm, the annual risk was 0.7% (0.5 to 1.0). The risk was higher in women (RR, 2.1[1.1 to 3.9]) and for aneurysms that were symptomatic (RR, 8.3 [4.0 to 17]), >10 mm (RR, 5.5 [3.3 to 9.4]), or in the posterior circulation (RR, 4.1 [1.5 to 11]).
CONCLUSIONS: Data on prevalence and risk of rupture vary considerably according to study design, study population, and aneurysm characteristics. If all available evidence with inherent overestimation and underestimation is taken together, for adults without risk factors for subarachnoid hemorrhage, aneurysms are found in approximately 2%. The vast majority of these aneurysms are small (=10 mm) and have an annual risk of rupture of approximately 0.7%.

PMID 9445359  Stroke. 1998 Jan;29(1):251-6.

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