尿吲哚反应性草酸钙结晶指数(iCOCI)试验诊断草酸钙尿石症的临床验证。

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

机构信息

Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand.

Division of Urology, Mahasarakham Hospital, Mahasarakham Province, 44000, Thailand.

出版信息

Sci Rep. 2020 May 20;10(1):8334. doi: 10.1038/s41598-020-65244-1.

DOI:10.1038/s41598-020-65244-1

PMID:32433482

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7239845/

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.

摘要

我们开发了一种吲哚反应性草酸钙结晶指数（iCOCI）检测方法，用于定量尿液沉淀草酸钙（CaOx）晶体的总能力。我们按照 STARD 指南进行了前瞻性队列研究，以评估尿 iCOCI 检测（指标检测）诊断结石病的准确性。共有 281 名参与者入组研究。在预诊断的 24 小时尿液样本中测定尿 iCOCI 水平。阳性尿 iCOCI（≥0.6 COM eqv.，g/L）占 51%（144/281），其余 49%（137/281）为阴性。随后进行非对比 CT 成像（参考标准）以明确诊断结石病，将参与者分为两组，非结石组（NSS，n=122）和结石形成组（SFS，n=159）。值得注意的是，只有在研究时当前有尿路结石的受试者被归类为 SFS。SFS 中的尿 iCOCI 水平明显高于 NSS。ROC 分析显示，区分 NSS 和所有 SFS 的曲线下面积（AUC）为 0.893（95%CI：0.855-0.932）。尿 iCOCI 检测诊断所有结石病的灵敏度、特异性、阳性预测值（PPV）、阴性预测值（NPV）、准确性、阳性似然比（LH）和阴性似然比（LH）分别为 87%、80%、84%、84%、83%、4.44 和 0.16。在 159 名 SFS 中，有 38 名被证实患有 CaOx 结石。在这 38 名 CaOx SFS 中，只有 2 名尿 iCOCI 检测结果为阴性。尿 iCOCI 检测区分 CaOx SFS 和 NSS 的 AUC 非常高（0.946，95%CI：0.914-0.978）。尿 iCOCI 检测诊断 CaOx 尿路结石的灵敏度、特异性、PPV、NPV、准确性、LH 和 LH 分别为 95%、86%、68%、98%、88%、6.80 和 0.06。结论是，我们临床验证了创新的非侵入性尿 iCOCI 检测对诊断结石病，尤其是 CaOx 结石具有高度准确性。尿 iCOCI 检测具有较高的灵敏度和 NPV，临床上拟用于 CaOx 结石的筛查试验。LH 为 0.06 表明尿 iCOCI 检测阴性结果高度准确，可以排除 CaOx 结石形成。需要注意的是，尿 iCOCI 水平以任意单位表示，与尿草酸盐的实际生理水平无关。