Clinical validation of urinary indole-reacted calcium oxalate crystallization index (iCOCI) test for diagnosing calcium oxalate urolithiasis

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.

Premature Senescence and Telomere Shortening Induced by Oxidative Stress From Oxalate, Calcium Oxalate Monohydrate, and Urine From Patients With Calcium Oxalate Nephrolithiasis

“…We used 24 h urine samples obtained from 10 participants as used for our previous study ( 29 ), 5 samples from patients with CaOx KS and 5 from age- and sex-matched individuals without stones (NS). The protocol using leftover specimens was approved by the Institutional Review Board of the Faculty of Medicine, Chulalongkorn University, Bangkok (IRB No.…”

“… † Measured by HPLC. ‡ Measured by iCOCI (indole-reacted calcium oxalate crystallization index) method ( 29 ). …”

“…HK-2 cells were treated with H 2 O 2 , sodium oxalate (NaOx) (Sigma-Aldrich), COM (Merck-Millipore), urine from patients with KS (n = 5), and urine from those without stones (NS urine) (n = 5) for 72 h. Cultures were treated at least in triplicate. According to their indole-reacted calcium oxalate crystallization index (iCOCI) levels ( 29 ), 24-h urine samples were pooled (from 10 samples), and divided into three groups, viz. : pooled urine with low or normal iCOCI levels from those without KS, pooled urine with high iCOCI from patients with KS, and pooled urine with very high iCOCI from patients with KS.…”

HydroZitLa inhibits calcium oxalate stone formation in nephrolithic rats and promotes longevity in nematode Caenorhabditis elegans

“…HydroZitLa and Uralyt-U had comparable efficacy on the reduction of urinary oxalate in nephrolithic rats, although it was more pronounced with HydroZitLa. Significant reduction of urinary iCOCI levels (indicator of the urinary competency of CaOx crystallization 38 ) was also observed in rats treated with HydroZitLa and Uralyt-U. These indicated that the potential of CaOx crystallization in the urine was decreased after HydroZitLa and Uralyt-U treatments.…”

“…Urinary oxalate and uric acid levels were measured by capillary electrophoresis (Beckman Coulter, CA, USA) separated at 25 °C with voltage of − 20 kV. Urinary iCOCI test was performed according to our previous report 38 .…”