A reduced glycine-to-taurine ratio of conjugated serum bile acids signifies an adaptive mechanism and is an early marker of outcome in acute respiratory distress syndrome.

Abstract

The accumulation of Bile Acids (BA) in serum is a common finding in critically ill patients and has been found in patients with Acute Respiratory Distress Syndrome (ARDS), where liver and biliary function could be essentially affected by the underlying disease process and subsequent therapeutic measures. We hypothesized that the glycine-to-taurine conjugation ratio (G/T-ratio) is predictive of outcome in ARDS patients and would support our previously published hypothesis that the BA profile reflects a (mal-) adaptive response of bile acid production when suffering from a disease or syndrome such as ARDS. In 70 patients with ARDS, we determined conjugated BA fractions from protein precipitated serum samples using a LC-MS/MS method and calculated the G/T-ratios, which were then compared with a healthy control group. In patients with ARDS, the G/T-ratio was markedly lower compared to the control group, due to an increase in taurine-conjugated BA. The G/T ratio was lowest on the day of diagnosis and increased steadily during the following days (control = 3.80 (2.28-4.44); day 0 = 1.79 (1.31-3.86); day 3 = 2.91 (1.71-5.68); day 5 = 2.28 (1.25-7.85), significant increases were found between day 0 and day 3 (p = 0.019) and between day 0 and day 5 (p = 0.031). G/T-ratio was significantly correlated with SAPS II score on day 0 (p = 0.009) and day 3 (p = 0.036) and with survival (p = 0.006). Regarding survival, the receiver-operator characteristic revealed an area-under-the-curve of 0.713 (CI 0.578-0.848), the Youden index revealed a G/T-ratio cut-off level of 2.835 (sensitivity 78.4%, specificity 63.2%). Our findings further support our previously published hypothesis that alterations in BA profiles represent adaptive mechanisms in states of severe disease. Our current study adds the finding of an increase in taurine-conjugated BA expressed by a decrease in the G/T-ratio of conjugated BA in serum. The G/T-ratio on day 3 using a threshold G/T-ratio of 2.8 was even associated with survival (p = 0.006); these results are yet to be confirmed by subsequent studies.