In cirrhosis, the development of ascites and the response to diuretics are determined by the RAAS (renin–angiotensin–aldosterone system) and renal sodium handling system. We hypothesized that SNPs (single nucleotide polymorphisms) affecting candidate genes in the RAAS and renal sodium handling pathway may influence initial diuretic responsiveness and affect clinical outcome in non-azotaemic cirrhotic patients with moderate ascites. We prospectively recruited 176 patients and 245 controls and determined their genetic polymorphisms for 24 SNPs of ten genes involved in the RAAS and renal sodium handling pathway. In cirrhotic patients with moderate ascites, multivariate analysis showed that diuretic unresponsiveness was predicted by a high basal plasma aldosterone level, by a high aldosterone/renin ratio and by specific risk genotypes of ACE (gene encoding angiotensin-converting enzyme), CYP11B2 (gene encoding aldosterone synthase) and ADDA (gene encoding α-adducin). This association between genetic polymorphisms and diuretic unresponsiveness was confirmed by an independent validation cohort. Notably, additive effects in relation to diuretic unresponsiveness were observed in cases where there was the simultaneous presence of the three risk genotypes. Among patients carrying any of the risk genotypes, more episodes of paracentesis and ascites-related readmission after 3 months of treatment, as well as a reduced 1-year survival rate, were observed. In addition to traditional predictors, our present study provides additional genetic and neurohormonal predictors that will help to identify diuretic non-responders among cirrhotic patients with moderate ascites. Among those carrying unfavourable risk genotypes, additional therapies, including paracentesis and albumin infusion, should be started as early as possible.
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Research Article|
August 09 2011
Identification of diuretic non-responders with poor long-term clinical outcomes: a 1-year follow-up of 176 non-azotaemic cirrhotic patients with moderate ascites
Ying-Ying Yang;
Ying-Ying Yang
1
*Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan
†Division of Preventive Medicine, Institute of Public Health, National Yang-Ming University, Taipei 11217, Taiwan
Correspondence: Dr Ying-Ying Yang (email [email protected]) or Dr Ming-Wei Lin (email [email protected]).
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Han-Chieh Lin;
Han-Chieh Lin
1
‡Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan
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Ming-Wei Lin;
†Division of Preventive Medicine, Institute of Public Health, National Yang-Ming University, Taipei 11217, Taiwan
Correspondence: Dr Ying-Ying Yang (email [email protected]) or Dr Ming-Wei Lin (email [email protected]).
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Chi-Jen Chu;
Chi-Jen Chu
‡Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan
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Fa-Yauh Lee;
Fa-Yauh Lee
§Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan
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Ming-Chih Hou;
Ming-Chih Hou
‡Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan
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Shou-Dong Lee;
Shou-Dong Lee
‡Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan
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Wei-Ping Lee;
Wei-Ping Lee
∥Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei 11217, Taiwan
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Tze-Tze Liu;
Tze-Tze Liu
¶Genome Research Center, National Yang-Ming University School of Medicine, Taipei 11217, Taiwan
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Tjin-Shing Jap
Tjin-Shing Jap
§Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan
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Publisher: Portland Press Ltd
Received:
January 13 2011
Revision Received:
June 02 2011
Accepted:
June 21 2011
Accepted Manuscript online:
June 21 2011
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2011 Biochemical Society
2011
Clin Sci (Lond) (2011) 121 (11): 509–521.
Article history
Received:
January 13 2011
Revision Received:
June 02 2011
Accepted:
June 21 2011
Accepted Manuscript online:
June 21 2011
Citation
Ying-Ying Yang, Han-Chieh Lin, Ming-Wei Lin, Chi-Jen Chu, Fa-Yauh Lee, Ming-Chih Hou, Shou-Dong Lee, Wei-Ping Lee, Tze-Tze Liu, Tjin-Shing Jap; Identification of diuretic non-responders with poor long-term clinical outcomes: a 1-year follow-up of 176 non-azotaemic cirrhotic patients with moderate ascites. Clin Sci (Lond) 1 December 2011; 121 (11): 509–521. doi: https://doi.org/10.1042/CS20110018
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