Pilot Study of Renal Urinary Biomarkers for Diagnosis of CKD of Uncertain Etiology
Pilot Study of Renal Urinary Biomarkers for Diagnosis of CKD of Uncertain Etiology
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DOI：
10.1016/j.ekir.2019.07.009
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发表时间：
2019-10-01
影响因子：
6
通讯作者：
Nanayakkara, Nishantha
中科院分区：
文献类型：
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作者：
Fernando, Buddhi N. T. W.;Alli-Shaik, Asfa;Nanayakkara, Nishantha
简介：病因不明的慢性肾脏病（CKDu）是一种新出现的慢性肾脏病（CKD）亚型，在某些热带国家导致显著的发病率和死亡率。虽然之前已经提出了CKDu的几个指标，但目前尚无法获得检测早期疾病或预测疾病进展的敏感和特异性测试。本研究重点评价了8种肾脏尿液标志物，即中性粒细胞明胶酶相关脂质运载蛋白（NGAL）、肾损伤分子-1（KIM 1）、胱抑素C（CST 3）、β 2微球蛋白（B2 M）、骨桥蛋白（OPN）、α 1微球蛋白（A1 M）、金属蛋白酶组织抑制剂1（TIMP 1）和视黄醇结合蛋白4（RBP 4），与假设，这些有不同的表达模式在CKDu患者。方法：进行了一项横断面研究，5个研究组，包括受试者CKDu，地方性CKD，非地方性CKD，地方性健康和非地方性健康对照。使用多重生物标志物测定法定量8种选定的肾脏生物标志物的尿液水平，并使用逻辑回归算法对数据进行系统分析，旨在提取可以从健康对照中无创地区分疾病组的最佳标志物组合。鉴定了包含A1 M、KIM 1和RBP 4的3-标志物特征组，以代表用于区分所有CKD类别的最佳最小标志物组合，包括CKDu，与健康对照相比，总体灵敏度>= 0.867，特异性>= 0.765。包括OPN、KIM 1和RBP 4的标志物组合显示出区分CKDu患者和CKD患者的高预测性能，灵敏度和特异性均>= 0.93，上级任何现有的非侵入性指标。总之，我们对以前与CKD相关的尿标志物的系统评价，一般来说，允许鉴定用于CKDu的早期诊断和确认的排他性标志物组组合。
Introduction: Chronic kidney disease of uncertain etiology (CKDu), an emerging chronic kidney disease (CKD) subtype, contributes to significant morbidity and mortality in certain tropical countries. Although several indicators of CKDu have been previously suggested, sensitive and specific tests to detect early disease or predict disease progression are currently unavailable. This study focused on evaluating 8 renal urinary markers, namely neutrophil gelatinase-associated lipocalin (NGAL), Kidney Injury Molecule-1 (KIM1), cystatin C (CST3), beta 2 microglobulin (B2M), osteopontin (OPN), alpha 1 microglobulin (A1M), tissue inhibitor of metalloproteinase 1 (TIMP1), and retinol binding protein 4 (RBP4), with the hypothesis that these have distinct expression patterns in patients with CKDu.Methods: A cross-sectional study was conducted with 5 study groups comprising subjects from CKDu, endemic CKD, nonendemic CKD, and endemic healthy and nonendemic healthy controls. The urinary levels of the 8 selected renal biomarkers were quantified using multiplex biomarker assay, and the data were subjected to systematic analysis using logistic regression algorithm aiming to extract the best marker combination that could distinctly identify the disease groups noninvasively from the healthy controls.Results: A 3-marker signature panel comprising A1M, KIM1, and RBP4 was identified to represent the best minimum marker combination for differentiating all CKD categories, including CKDu, from healthy controls with an overall sensitivity of >= 0.867 and specificity >= 0.765. The marker combination comprising OPN, KIM1, and RBP4 showed high predictive performance for distinguishing patients with CKDu from patients with CKD with both sensitivity and specificity >= 0.93, which was superior to any existing noninvasive indicator.Conclusion: In all, our systematic evaluation of urinary markers previously linked to CKD, in general, allowed identification of exclusive marker panel combination for early diagnosis and confirmation of CKDu.