Abstract
An indole-reacted calcium oxalate crystallization index (iCOCI) test was developed to quantify the total competence of urine to precipitate calcium oxalate (CaOx) crystals. We conducted the prospective cohort study in accordance with the STARD guideline to evaluate the accuracy of urinary iCOCI test (index test) for diagnosing urolithiasis. A total of 281 participants were recruited for the study. Levels of urinary iCOCI were determined in the pre-diagnostic 24-h urine samples. Positive urinary iCOCI (≥ 0.6 COM eqv., g/L) was accounted for 51% (144/281), and the rest of 49% (137/281) were negative. Non-contrast CT imaging (reference standard) was subsequently performed for the definite diagnosis of urolithiasis to divide the participants into two groups, non-stone subjects (NSS, n = 122) and stone-forming subjects (SFS, n = 159). It should be noted that only subjects who currently had urinary stone at the time of study were classified as SFS. Urinary iCOCI levels in the SFS were significantly higher than the NSS. ROC analysis revealed an area under curve (AUC) of 0.893 (95% CI: 0.855–0.932) in separating NSS from all SFS. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, positive likelihood ratio (LH+) and negative likelihood ratio (LH−) of urinary iCOCI test for diagnosis of all urolithiasis were 87%, 80%, 84%, 84%, 83%, 4.44 and 0.16, respectively. Of 159 SFS, 38 were confirmed to have CaOx stones. Among these 38 CaOx SFS, only 2 had negative urinary iCOCI test. The AUC of urinary iCOCI test for separating CaOx SFS from NSS was markedly high (0.946, 95% CI: 0.914–0.978). Sensitivity, specificity, PPV, NPV, accuracy, LH+ and LH− of urinary iCOCI test for diagnosing CaOx urolithiasis were 95%, 86%, 68%, 98%, 88%, 6.80 and 0.06, respectively. Conclusion, we clinically validated that an innovative non-invasive urinary iCOCI test was highly accurate to diagnose urolithiasis, especially CaOx stone. With its high sensitivity and NPV, urinary iCOCI test is clinically intended to use as a screening test for CaOx urolithiasis. LH− of 0.06 indicates that negative result of urinary iCOCI test is highly accurate to rule out the CaOx stone formation. It is noted that urinary iCOCI level is expressed as arbitrary unit, and it is not directly related to the actual physiological level of urinary oxalate.
Highlights
An indole-reacted calcium oxalate crystallization index test was developed to quantify the total competence of urine to precipitate calcium oxalate (CaOx) crystals
An innovative test with high accuracy, simple procedure and cost-effectiveness for assessing the likelihood of having or not having urolithiasis has not been established for the routine use
Both Bonn Risk Index (BRI) and calcium oxalate crystallization index (COCI) tests were reported with high diagnostic power, these studies were case-control retrospective studies, and the determination of BRI and COCI were performed in the post-diagnostic urine specimens
Summary
An indole-reacted calcium oxalate crystallization index (iCOCI) test was developed to quantify the total competence of urine to precipitate calcium oxalate (CaOx) crystals. The urinary COCI test has high discriminatory power (83% sensitivity, 97% specificity, 90% accuracy) in separating stone-forming subjects (SFS) from the age- and sex-matched non-stone subjects (NSS) with an AUC of 0.9499 (95%CI: 0.9131–0.9868). With this diagnostic accuracy, the urinary COCI test is promising for clinical implementation. The clinically intended use of urinary iCOCI test is to be a screening test or a medical surveillance for assessing the likelihood of having urinary stone formation, CaOx stone (similar to cholesterol measurement for assessing the risk of heart disease), in the defined population who have higher risk of stone formation than normal, e.g., individuals who have positive family history of urolithiasis[16], men aged over 30 years old[17] and women after menopause[18]. Since a screening test does not function to diagnose the disease, and individuals with screening test positive subsequently require further testing with a diagnostic test for the disease confirmation[19], we believe that the use of urinary iCOCI test would significantly reduce the number of individuals requiring CT scan for diagnosis of urinary stones, and drastically reducing the imaging cost and radiation exposure
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