Development of calcium oxalate crystallization index for estimating lithogenic potential in urines of patients with nephrolithiasis

Abstract

Nephrolithiasis is a significant health problem in Thailand. It is known that urinary crystals are building blocks of kidney calculi, and urinary supersaturation triggers crystal formation. The most common type of lithogenic crystals is calcium oxalate (CaOx). In this study, a new test, designated CaOx crystallization index (COCI), was developed to distinguish nephrolithiasis patients from healthy individuals based on the urinary crystallization capability. The effect of urine volume, oxalate, phosphate, citrate, potassium and sodium on COCI values was investigated. COCI values were determined in 24-hr urine obtained from nephrolithiasis patients (n = 72) and age- and sex-matched healthy controls (n = 71). The diagnostic potential of the urinary COCI test was evaluated. Increases in urine oxalate and phosphate caused increase in COCI values. In contrast, increases in urine volume and citrate caused decreased COCI values. Urinary COCI values of nephrolithiasis group were significantly higher than that of healthy group. Importantly, asymptomatic kidney calculi were detected by ultrasound imaging in two healthy subjects with elevated COCI values. Based on receiver operating characteristic (ROC) analysis, an area under ROC curve of the urinary COCI test was 0.9499 (95%CI: 0.9131-0.9868), indicated that this test had excellent discriminatory power to separate nephrolithiasis from healthy subjects. At the cutoff of 165 mg oxalate equivalence/day, the COCI test provided sensitivity, specificity and accuracy of 83.33, 97.18 and 90.21%, respectively. In conclusion, the COCI test was successfully established, and its values were primarily dependent on urine volume, oxalate, phosphate and citrate. The test provided high sensitivity and specificity for clinically discriminating the nephrolithiasis patients from healthy population. We suggest that the COCI test is a cheap, simple, non-invasive and reliable method that could be implemented in hospital laboratories to identify individuals at risk of kidney stone formation as well as those with asymptomatic urinary calculi or early stage of nephrolithiasis.