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*, 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

*此作品的通信作者

研究成果: Article同行評審

9 引文 斯高帕斯(Scopus)

摘要

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.

原文English
頁(從 - 到)509-521
頁數13
期刊Clinical Science
121
發行號11
DOIs
出版狀態Published - 12月 2011

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