PURPOSECarbonic anhydrase-2 (CA-2) plays a role in mineralization and calcification in organism. Strong evidence suggests that CA-2 is associated with urolithiasis. However, the relationship between CA-2 and urinary stone remains unclear. The study aimed to assess the association of urine CA-2 (uCA-2) level and the potential risk of urinary stone.METHODSFrom March 2017 to November 2019, a prospective cohort study was conducted on patients with urinary stones and healthy subjects to determine the pretreatment uCA-2 level detection by Enzyme linked immunosorbent assay (ELISA). The difference of uCA-2 level between patients with urinary stones and healthy subjects was compared. Then comparison between stone patients with complications and without complications was carried out as well as correlation analysis to detect factors associated with biomarker expression.RESULTS118 patients with urinary stones were into urinary stones group and 42 healthy subjects were into healthy control group. The mean pretreatment uCA-2 level was significantly higher in patients with urinary stones group than healthy controls group (P=0.028). Furthermore, The uCA-2 level was positive correlation with urinary stones complications (R=0.379, P=0.000), especially pain complications (R=0.524, P=0.000) and hematuria complications (R=0.374, P=0.000). Receiver operating characteristic curve (ROC) analysis that a uCA-2 level threshold of 10.94 ng/mL had 83.67% sensitivity and 68.12% specificity for predicting urinary stones complications. CONCLUSIONSExcessive uCA-2 excretion is a major risk factor for urinary stone. Our findings suggested that uCA-2 may be used as an unappreciated biomarker for the diagnosis urinary stone in patients and to predict its complications.