Supplementary Material for: Significance of Neutrophil Gelatinase-Associated Lipocalin as a Biomarker for the Diagnosis of Diabetic Kidney Disease: A Systematic Review and Meta-Analysis

<b><i>Background:</i></b> Neutrophil gelatinase-associated lipocalin (NGAL) is a promising marker for the diagnosis of diabetic kidney disease (DKD), but its utility is currently debated. This meta-analysis aims to evaluate the diagnostic value of NGAL for DKD. <b><i>Method:</i></b> MEDLINE, Embase, ­Cochrane Library, CNKI, and CBM databases were searched up to April 13, 2019. In bivariate random-effect models, the diagnostic performance of NGAL for DKD was assessed using pooled estimates of sensitivity, specificity, likelihood ratio, diagnostic odds ratio, and hierarchical summary receiver-operating characteristic analysis. <b><i>Results:</i></b> Nineteen studies were eligible for the meta-analysis. Serum NGAL had a pooled sensitivity and specificity of 0.79 (95% confidence intervals [CI] 0.60–0.91) and 0.87 (0.75–0.93) (7 studies, 1,238 patients). The pooled positive likelihood ratio (LR+) and negative likelihood ratio (LR–) were 5.97 (3.03–11.76) and 0.24 (0.11–0.51). For urine NGAL, the pooled sensitivity, specificity, LR+, and LR– were 0.85 (0.74–0.91), 0.74 (0.57–0.86), 3.26 (1.87–5.67), and 0.21 (0.12–0.35), respectively (10 studies, 1,369 patients). The pooled sensitivity and specificity for kidney disease in normoalbuminuric patients with diabetes was 0.90 (0.82–0.95) and 0.97 (0.90–0.99) for both serum NGAL and 0.94 (0.87–0.98) and 0.90 (0.81–0.96) for urine NGAL (4 studies, 221 patients). NGAL appeared to perform similarly in subgroup analysis. <b><i>Conclusion:</i></b> The meta-analysis has shown that NGAL may be useful for DKD classification and also has a potential diagnostic value for normoalbuminuric kidney disease. Large-scale prospective studies are required to clarify its role in the diagnosis and risk stratification of patients with DKD.

**背景：** 中性粒细胞明胶酶相关脂质运载蛋白（Neutrophil gelatinase-associated lipocalin, NGAL）是诊断糖尿病肾病（diabetic kidney disease, DKD）的极具潜力的标志物，但其临床应用价值目前尚存争议。本荟萃分析旨在评估NGAL对糖尿病肾病的诊断价值。**方法：** 检索截至2019年4月13日的MEDLINE、Embase、Cochrane图书馆、中国知网（CNKI）及中国生物医学文献数据库（CBM）。采用双变量随机效应模型，通过合并灵敏度、特异度、似然比、诊断比值比以及分层综合受试者工作特征分析，评估NGAL对糖尿病肾病的诊断效能。**结果：** 最终有19项研究符合本荟萃分析的纳入标准。血清NGAL的合并灵敏度与特异度分别为0.79（95%置信区间[CI] 0.60~0.91）和0.87（0.75~0.93），纳入7项研究，共1238例患者；其合并阳性似然比（LR+）与阴性似然比（LR–）分别为5.97（3.03~11.76）和0.24（0.11~0.51）。尿液NGAL的合并灵敏度、特异度、阳性似然比及阴性似然比分别为0.85（0.74~0.91）、0.74（0.57~0.86）、3.26（1.87~5.67）及0.21（0.12~0.35），纳入10项研究，共1369例患者。针对正常白蛋白尿糖尿病患者的肾病亚组分析显示，血清NGAL的合并灵敏度与特异度分别为0.90（0.82~0.95）和0.97（0.90~0.99），尿液NGAL则分别为0.94（0.87~0.98）和0.90（0.81~0.96），纳入4项研究，共221例患者；亚组分析中NGAL的诊断效能表现相似。**结论：** 本荟萃分析结果表明，NGAL可用于糖尿病肾病的分型，同时对正常白蛋白尿糖尿病合并肾病亦具有潜在诊断价值。未来需开展大规模前瞻性研究，以明确NGAL在糖尿病肾病患者诊断及风险分层中的应用价值。