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High expression of a vascular stricture‐related marker is predictive of an early response to tolvaptan, and a low fractional excretion of sodium is predictive of a poor long‐term survival after tolvaptan administration for liver cirrhosis
Author(s) -
Adachi Takuya,
Takaki Akinobu,
Sato Shuichi,
Tobita Hiroshi,
Kobashi Haruhiko,
Kinomura Masaru,
Nakatsuka Atsuko,
Oyama Atsushi,
Wada Nozomu,
Sakata Masahiro,
Takeuchi Yasuto,
Yasunaka Tetsuya,
Onishi Hideki,
Shiraha Hidenori,
Okada Hiroyuki
Publication year - 2020
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/hepr.13573
Subject(s) - tolvaptan , medicine , fractional excretion of sodium , furosemide , creatinine , ascites , renal function , hyponatremia , urology , cirrhosis , gastroenterology , asymmetric dimethylarginine , diuretic , predictive marker , endocrinology , cardiology , cancer , arginine , biochemistry , chemistry , amino acid
Aim Tolvaptan is a newly available diuretic that has a specific function in water reabsorption inhibition. Given that spironolactone or furosemide induces the aggravation of cirrhotic hyponatremia and dehydration, tolvaptan affects the management strategy of liver cirrhosis. Representative predictive markers of its response include renal function‐related markers such as urea nitrogen or creatinine. However, vascular function‐related markers have not been well investigated. We investigated the effect of the vascular function‐related marker asymmetric dimethylarginine (ADMA) and the effective arterial blood volume (EABV) marker, fractional excretion of sodium (FENa), on the early tolvaptan response and survival in liver cirrhosis. Methods We prospectively recruited 49 patients who required add‐on tolvaptan for refractory ascites or edema. Laboratory data were obtained immediately before and 1 day after tolvaptan administration. Patients exhibiting >1.5 kg weight loss after 1 week were categorized as early responders to tolvaptan. Patients were followed for a median of 200 days and were assessed for survival. Results Early responders showed lower creatinine levels (<1.0 mg/dL), and higher ADMA levels (≥0.61 nmol/mL) than others in a multivariate analysis. Patients with a shorter survival were positive for hepatocellular carcinoma and had a low FENa (<0.35%). Conclusion Early responders showed higher ADMA levels reflecting vascular stricture, suggesting that higher vascular tonus is required for a tolvaptan early response. Patients with a shorter survival showed a lower FENa, reflecting a lower EABV and suggesting that adequate EABV is required for the prolonged survival after tolvaptan administration.