Clinical characteristics and genetic backgrounds of Japanese patients with atypical hemolytic uremic syndrome

被引:41
作者
Fujisawa, Madoka [1 ]
Kato, Hideki [1 ]
Yoshida, Yoko [1 ]
Usui, Tomoko [1 ]
Takata, Munenori [2 ]
Fujimoto, Mika [3 ]
Wada, Hideo [4 ]
Uchida, Yumiko [5 ]
Kokame, Koichi [5 ]
Matsumoto, Masanori [6 ]
Fujimura, Yoshihiro [7 ]
Miyata, Toshiyuki [8 ]
Nangaku, Masaomi [1 ]
机构
[1] Univ Tokyo, Div Nephrol & Endocrinol, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan
[2] Univ Tokyo, Clin Res Support Ctr CresCent, Tokyo, Japan
[3] Mie Univ, Dept Cardiol & Nephrol, Grad Sch Med, Tsu, Mie, Japan
[4] Mie Univ, Dept Mol & Lab Med, Grad Sch Med, Tsu, Mie, Japan
[5] Natl Cerebral & Cardiovasc Ctr, Dept Mol Pathogenesis, Suita, Osaka, Japan
[6] Nara Med Univ, Dept Blood Transfus Med, Nara, Japan
[7] Japanese Red Cross Kinki Block Blood Ctr, Ibaraki, Japan
[8] Natl Cerebral & Cardiovasc Ctr, Dept Cerebrovasc Med, Suita, Osaka, Japan
基金
日本学术振兴会;
关键词
Atypical hemolytic uremic syndrome; Thrombotic microangiopathy; Congenital disorder; Complement; Epidemiology; COMPLEMENT MUTATIONS; DISEASE; ECULIZUMAB; OUTCOMES; IMPACT;
D O I
10.1007/s10157-018-1549-3
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Background Atypical hemolytic uremic syndrome (aHUS) is caused by complement overactivation, and its presentation and prognosis differ according to the underlying molecular defects. The aim of this study was to characterize the genetic backgrounds of aHUS patients in Japan and to elucidate the associations between their genetic backgrounds, clinical findings, and outcomes. Methods We conducted a nationwide epidemiological survey of clinically diagnosed aHUS patients and examined 118 patients enrolled from 1998 to 2016 in Japan. We screened variants of seven genes related to complement and coagulation, as well as positivity for anti-CFH antibodies, and assessed clinical manifestations, laboratory findings, and clinical course. Results The most frequent genetic abnormalities were in C3 (31%) and the frequency of CFH variants was relatively low (10%) compared to Western countries. The predominant variant in this cohort was C3 p.11157T (23%), which was related to favorable outcomes despite frequent relapses. A total of 72% of patients received plasma therapy, while 42% were treated with eculizumab. The prognosis of Japanese aHUS patients was relatively favorable, with a total mortality rate of 5.4% and a renal mortality rate of 15%. Conclusions The common occurrence of genotype C3, especially the p.11157T variant was the characteristic of the genetic backgrounds of Japanese aHUS patients that differed from those of Caucasian patients. In addition, the favorable prognosis of patients with the unique C3 p.11157T variant indicates that understanding the clinical characteristics of individual gene alterations is important for predicting prognosis and determining therapeutic strategies in aHUS.
引用
收藏
页码:1088 / 1099
页数:12
相关论文
共 27 条
[1]   Predictive Features of Severe Acquired ADAMTS13 Deficiency in Idiopathic Thrombotic Microangiopathies: The French TMA Reference Center Experience [J].
Coppo, Paul ;
Schwarzinger, Michael ;
Buffet, Marc ;
Wynckel, Alain ;
Clabault, Karine ;
Presne, Claire ;
Poullin, Pascale ;
Malot, Sandrine ;
Vanhille, Philippe ;
Azoulay, Elie ;
Galicier, Lionel ;
Lemiale, Virginie ;
Mira, Jean-Paul ;
Ridel, Christophe ;
Rondeau, Eric ;
Pourrat, Jacques ;
Girault, Stephane ;
Bordessoule, Dominique ;
Saheb, Samir ;
Ramakers, Michel ;
Hamidou, Mohamed ;
Vernant, Jean-Paul ;
Guidet, Bertrand ;
Wolf, Martine ;
Veyradier, Agnes .
PLOS ONE, 2010, 5 (04)
[2]   Pathogenic Variants in Complement Genes and Risk of Atypical Hemolytic Uremic Syndrome Relapse after Eculizumab Discontinuation [J].
Fakhouri, Fadi ;
Fila, Marc ;
Provot, Francois ;
Delmas, Yahsou ;
Barbet, Christelle ;
Chatelet, Valerie ;
Rafat, Cedric ;
Cailliez, Mathilde ;
Hogan, Julien ;
Servais, Aude ;
Karras, Alexandre ;
Makdassi, Raifah ;
Louillet, Feriell ;
Coindre, Jean-Philippe ;
Rondeau, Eric ;
Loirat, Chantal ;
Fremeaux-Bacchi, Veronique .
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2017, 12 (01) :50-59
[3]   Analysis of genetic and predisposing factors in Japanese patients with atypical hemolytic uremic syndrome [J].
Fan, Xinping ;
Yoshida, Yoko ;
Honda, Shigenori ;
Matsumoto, Masanori ;
Sawada, Yugo ;
Hattori, Motoshi ;
Hisanaga, Shuichi ;
Hiwa, Ryosuke ;
Nakamura, Fumihiko ;
Tomomori, Maiko ;
Miyagawa, Shinichiro ;
Fujimaru, Rika ;
Yamada, Hiroshi ;
Sawai, Toshihiro ;
Ikeda, Yuhachi ;
Iwata, Naoyuki ;
Uemura, Osamu ;
Matsukuma, Eiji ;
Aizawa, Yoshiaki ;
Harada, Hiroshi ;
Wada, Hideo ;
Ishikawa, Eiji ;
Ashida, Akira ;
Nangaku, Masaomi ;
Miyata, Toshiyuki ;
Fujimura, Yoshihiro .
MOLECULAR IMMUNOLOGY, 2013, 54 (02) :238-246
[4]   Genetic and functional analyses of membrane cofactor protein (CD46) mutations in atypical hemolytic uremic syndrome [J].
Fremeaux-Bacchi, Veronique ;
Moulton, Elizabeth A. ;
Kavanagh, David ;
Dragon-Durey, Marie-Agnes ;
Blouin, Jacques ;
Caudy, Amy ;
Arzouk, Nadia ;
Cleper, Roxanna ;
Francois, Maud ;
Guest, Genevieve ;
Pourrat, Jacques ;
Seligman, Roland ;
Fridman, Wolf Herman ;
Loirat, Chantal ;
Atkinson, John P. .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2006, 17 (07) :2017-2025
[5]   Genetics and Outcome of Atypical Hemolytic Uremic Syndrome: A Nationwide French Series Comparing Children and Adults [J].
Fremeaux-Bacchi, Veronique ;
Fakhouri, Fadi ;
Gamier, Arnaud ;
Bienaime, Frank ;
Dragon-Durey, Marie-Agnes ;
Ngo, Stephanie ;
Moulin, Bruno ;
Servais, Aude ;
Provot, Francois ;
Rostaing, Lionel ;
Burtey, Stephane ;
Niaudet, Patrick ;
Deschenes, Georges ;
Lebranchu, Yvon ;
Zuber, Julien ;
Loirat, Chantal .
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2013, 8 (04) :554-562
[6]   Atypical hemolytic uremic syndrome and C3 glomerulopathy: conclusions from a "Kidney Disease: Improving Global Outcomes" (KDIGO) Controversies Conference [J].
Goodship, Timothy H. J. ;
Cook, H. Terence ;
Fakhouri, Fadi ;
Fervenza, Fernando C. ;
Fremeaux-Bacchi, Veronique ;
Kavanagh, David ;
Nester, Carla M. ;
Noris, Marina ;
Pickering, Matthew C. ;
de Cordoba, Santiago Rodriguez ;
Roumenina, Lubka T. ;
Sethi, Sanjeev ;
Smith, Richard J. H. .
KIDNEY INTERNATIONAL, 2017, 91 (03) :539-551
[7]   Clinical guides for atypical hemolytic uremic syndrome in Japan [J].
Kato, Hideki ;
Nangaku, Masaomi ;
Hataya, Hiroshi ;
Sawai, Toshihiro ;
Ashida, Akira ;
Fujimaru, Rika ;
Hidaka, Yoshihiko ;
Kaname, Shinya ;
Maruyama, Shoichi ;
Yasuda, Takashi ;
Yoshida, Yoko ;
Ito, Shuichi ;
Hattori, Motoshi ;
Miyakawa, Yoshitaka ;
Fujimura, Yoshihiro ;
Okada, Hirokazu ;
Kagami, Shoji .
CLINICAL AND EXPERIMENTAL NEPHROLOGY, 2016, 20 (04) :536-543
[8]  
Kobayashi N, 1983, Bibl Haematol, P265
[9]   Complement, thrombotic microangiopathy and disseminated intravascular coagulation [J].
Kurosawa S. ;
Stearns-Kurosawa D.J. .
Journal of Intensive Care, 2 (1)
[10]   Atypical hemolytic uremic syndrome: Korean pediatric series [J].
Lee, Jiwon M. ;
Park, Young Seo ;
Lee, Joo Hoon ;
Park, Se Jin ;
Shin, Jae Il ;
Park, Yong-Hoon ;
Yoo, Kee Hwan ;
Cho, Min Hyun ;
Kim, Su-Young ;
Kim, Seong Heon ;
Namgoong, Mee Kyung ;
Lee, Seung Joo ;
Lee, Jun Ho ;
Cho, Hee Yeon ;
Han, Kyoung Hee ;
Kang, Hee Gyung ;
Ha, Il Soo ;
Bae, Jun-Seok ;
Kim, Nayoung K. D. ;
Park, Woong-Yang ;
Cheong, Hae Il .
PEDIATRICS INTERNATIONAL, 2015, 57 (03) :431-438