A novel sodium overload test predicting ascites decompensation in rats with CCl4-induced cirrhosis

Background/Aims We aimed to develop a non-invasive test to identify the initial alterations of sodium homeostasis and prospectively predict decompensation in preascitic cirrhotic rats. Methods The sodium overload test (SOT) was performed in control (CT) and CCl4-induced cirrhotic rats (CH) by calculating the percentage of sodium excreted in the urine after NaCl oral administration (0.5 g/kg). Liver fibrosis was quantified by image cytometry. Results From the 8th week of CCl4 intoxication, while the daily sodium balance did not change in CH and CT, SOT became significantly lower in the former (62.1±13.2 vs 78.8±13.2%; P=0.035). At sacrifice, ascites was only present in one animal. The degree of liver fibrosis correlated with SOT. In subsequent experiments, 17 cirrhotic rats developed ascites between the 9th and 14th weeks. SOT remained stable up to 3 weeks before ascites appearance, while it fell significantly to 35±19 and 26±21% at 2 and 1 week before ascites diagnosis, respectively. Nearly all the rats (95%) with a SOT<60% developed ascites within 3 weeks. Conclusions In preascitic cirrhotic rats, SOT unveils sodium metabolism abnormalities earlier than the daily sodium balance and prospectively predicts ascites appearance, identifying rats in a homogeneous stage of cirrhosis, which is essential in pathophysiological studies on sodium retention.