Urinary neutrophil gelatinase-associated lipocalin as a biomarker of nephritis in childhood-onset systemic lupus erythematosus
Urinary neutrophil gelatinase-associated lipocalin as a biomarker of nephritis in childhood-onset systemic lupus erythematosus
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DOI：
10.1002/art.22008
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发表时间：
2006-08-01
影响因子：
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通讯作者：
Devarajan, Prasad
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文献类型：
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作者：
Brunner, Hermine I.;Mueller, Michelle;Devarajan, Prasad
目标。系统性红斑狼疮(SLE)的肾脏受累与预后不良有关。目前可用的肾脏生物标志物对诊断SLE肾炎相对不敏感和非特异性。以往的研究表明，中性粒细胞明胶酶相关脂钙蛋白(NGAL)是急性肾损伤的高质量肾脏生物标志物，但其在SLE中的作用尚不清楚。我们进行了这项研究，以确定尿NGAL排泄与SLE疾病活动或损害的关系，重点是肾炎。在一项双盲横断面研究中，对35名在16岁之前被诊断为患有系统性红斑狼疮(儿童期SLE)的患者进行了疾病活动性(使用2000年更新的系统性红斑狼疮疾病活动指数)和损害(使用系统性红斑狼疮国际协作诊所/美国风湿病学会SLE损害指数)的评估。获得有关当前肾功能和疾病标志物的信息，并与酶联免疫吸附试验测定的NGAL水平(尿肌酐ng/mg)进行比较。8例幼年特发性关节炎(JIA)患儿作为对照。NGAL水平与患者的年龄、体重、身高、性别或种族无关。儿童期起病的系统性红斑狼疮患者的NGAL水平显著高于JIA患者(P<；0.0001)。NGAL水平与肾脏疾病活动性和肾脏损害有很强到中等程度的相关性(在两个比较中，Spearman‘s r>；=0.47，P<；0.0001)，但与肾脏外疾病活动性或肾外损害无关。NGAL-GT；0.6 ng/mg尿肌酐水平对诊断经活检证实为肾炎的儿童期SLE患者的敏感性为90%，特异性为100%。尿NGAL是儿童期SLE肾炎的潜在生物标志物。目前的研究结果需要在更大的队列中进行验证，以更准确地描述与不同SLE表型相关的尿NGAL排泄量。
Objective. Renal involvement in systemic lupus erythematosus (SLE) is associated with poor prognosis. Currently available renal biomarkers are relatively insensitive and nonspecific for diagnosing SLE nephritis. Previous research suggests that neutrophil gelatinase-associated lipocalin (NGAL) is a high-quality renal biomarker of acute kidney injury, while its usefulness in SLE is unclear. We undertook this study to determine the relationship between urinary NGAL excretion and SLE disease activity or damage, with a focus on nephritis.Methods. A cohort of 35 patients diagnosed as having SLE prior to age 16 years (childhood-onset SLE) was assessed for disease activity (using the Systemic Lupus Erythematosus Disease Activity Index 2000 update) and damage (using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology SLE Damage Index) in a double-blind, cross-sectional study. Information on current markers of renal function and disease was obtained and compared with NGAL levels (ng/mg of urinary creatinine) measured by enzyme-linked immunosorbent assay. Eight children with juvenile idiopathic arthritis (JIA) served as controls.Results. NGAL levels did not differ with the age, weight, height, sex, or race of the patients. Patients with childhood-onset SLE had significantly higher NGAL levels than did those with JIA (P < 0.0001). NGAL levels were strongly to moderately correlated with renal disease activity and renal damage (Spearman's r >= 0.47, P < 0.0001 for both comparisons), but not with extrarenal disease activity or extrarenal damage. NGAL levels of > 0.6 ng/mg urinary creatinine were 90% sensitive and 100% specific for identifying childhood-onset SLE patients with biopsy-proven nephritis.Conclusion. Urinary NGAL is a promising potential biomarker of childhood-onset SLE nephritis. The results of the current study require validation in a larger cohort to more accurately delineate urinary NGAL excretion in relation to the diverse SLE phenotypes.