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Abstract：
OBJECTIVE: Despite much research about lupus nephritis, none of the urinary biomarkers has been proven to be truly reflecting lupus nephritis activity, response to treatment, or prognosis. We aimed to study urinary biomarkers in lupus nephritis and test their relation to kidney damage.
METHODS: Forty patients with systemic lupus erythematosus (SLE) were divided into two graoups: (1) lupus nephritis group with biopsy-proven proliferative lupus nephritis (classes III and IV) and who did not receive immunosuppressive drugs within the preceding 3 months except for glucocorticoids and (2) lupus non-nephritis group with SLE patients without any renal manifestation. We assessed disease activity by the SLE disease activity index. uNGAL, uKim-1, uNGAL to urinary creatinine excretion (mg/dl), and uKim-1 to urinary creatinine excretion were measured in random spot urine samples at the time of renal biopsy and 6 months after the induction therapy.
RESULTS: The LN group before treatment showed higher levels of uNGAL and uKIM-1 (P-value < 0.001). ROC analysis showed that uNGAL at level of > 59 has a 95 % sensitivity, a 100 % specificity, and an AUC = 0.996 in the ability to diagnose LN. While the uKIM-1 ROC showed that at level of > 1.6, it has an 85 % sensitivity, an 80 % specificity, and an AUC = 0.919. uNGAL and uKIM levels were significantly lower after treatment (P-value < 0.001). No significant correlations were found between urinary markers before and after treatment with other clinical, inflammatory, and serological markers of lupus nephritis.
CONCLUSIONS: uNGAL, uKIM, uNGAL/Creat ratio, and uKIM/Creat ratio can be used as a predictor and a marker of disease activity for lupus nephritis. Key Points • Renal biopsy is the current standard for diagnosis of lupus nephritis and none of the urinary biomarkers has been fully concluded to have a diagnostic power to reflect the activity or the response to treatment. • However, based on the finding of the current study, uNGAL, uKIM, uNGAL/Creat ratio, and uKIM/Creat ratio showed significant diagnostic performance and were powerful indices of renal involvement in systemic lupus patients and as markers of disease activity.
METHODS: Forty patients with systemic lupus erythematosus (SLE) were divided into two graoups: (1) lupus nephritis group with biopsy-proven proliferative lupus nephritis (classes III and IV) and who did not receive immunosuppressive drugs within the preceding 3 months except for glucocorticoids and (2) lupus non-nephritis group with SLE patients without any renal manifestation. We assessed disease activity by the SLE disease activity index. uNGAL, uKim-1, uNGAL to urinary creatinine excretion (mg/dl), and uKim-1 to urinary creatinine excretion were measured in random spot urine samples at the time of renal biopsy and 6 months after the induction therapy.
RESULTS: The LN group before treatment showed higher levels of uNGAL and uKIM-1 (P-value < 0.001). ROC analysis showed that uNGAL at level of > 59 has a 95 % sensitivity, a 100 % specificity, and an AUC = 0.996 in the ability to diagnose LN. While the uKIM-1 ROC showed that at level of > 1.6, it has an 85 % sensitivity, an 80 % specificity, and an AUC = 0.919. uNGAL and uKIM levels were significantly lower after treatment (P-value < 0.001). No significant correlations were found between urinary markers before and after treatment with other clinical, inflammatory, and serological markers of lupus nephritis.
CONCLUSIONS: uNGAL, uKIM, uNGAL/Creat ratio, and uKIM/Creat ratio can be used as a predictor and a marker of disease activity for lupus nephritis. Key Points • Renal biopsy is the current standard for diagnosis of lupus nephritis and none of the urinary biomarkers has been fully concluded to have a diagnostic power to reflect the activity or the response to treatment. • However, based on the finding of the current study, uNGAL, uKIM, uNGAL/Creat ratio, and uKIM/Creat ratio showed significant diagnostic performance and were powerful indices of renal involvement in systemic lupus patients and as markers of disease activity.
摘要：
目标：尽管有很多关于狼疮性肾炎的研究，没有一种尿液生物标志物被证明能真正反映狼疮性肾炎的活动，对治疗的反应，或预后。我们旨在研究狼疮性肾炎中的尿生物标志物，并测试它们与肾脏损害的关系。
方法：将40例系统性红斑狼疮（SLE）患者分为两个组：（1）狼疮性肾炎组，经活检证实的增生性狼疮性肾炎（III级和IV级），除糖皮质激素外，在前3个月内未接受免疫抑制药物治疗；（2）狼疮性非肾炎组，SLE患者无任何肾脏表现。我们通过SLE疾病活动指数评估疾病活动。uNGAL,uKim-1，uNGAL对尿肌酐排泄（mg/dl），在肾活检时和诱导治疗后6个月，在随机点尿样中测量uKim-1到尿肌酐排泄量。
结果：治疗前LN组显示uNGAL和uKIM-1水平较高（P值<0.001）。ROC分析表明，uNGAL在>59的水平具有95%的敏感性，100%的特异性，诊断LN的能力为AUC=0.996。而uKIM-1ROC显示，在>1.6的水平，它具有85%的灵敏度，80%的特异性，和AUC=0.919。治疗后uNGAL和uKIM水平显著降低(P值<0.001)。治疗前后尿路指标与其他临床指标无显著相关性,炎症，和狼疮性肾炎的血清学标志物。
结论：uNGAL，uKIM,uNGAL/Creat比率,和uKIM/Creat比值可作为狼疮性肾炎疾病活动性的预测因子和标志。要点•肾活检是目前诊断狼疮性肾炎的标准,并且没有一种尿生物标志物被完全认为具有反映活性或对治疗的反应的诊断能力。•However,根据当前研究的发现，uNGAL,uKIM,uNGAL/Creat比率,和uKIM/Creat比值显示出显著的诊断性能,是系统性红斑狼疮患者肾脏受累的有力指标,也是疾病活动的标志.
方法：将40例系统性红斑狼疮（SLE）患者分为两个组：（1）狼疮性肾炎组，经活检证实的增生性狼疮性肾炎（III级和IV级），除糖皮质激素外，在前3个月内未接受免疫抑制药物治疗；（2）狼疮性非肾炎组，SLE患者无任何肾脏表现。我们通过SLE疾病活动指数评估疾病活动。uNGAL,uKim-1，uNGAL对尿肌酐排泄（mg/dl），在肾活检时和诱导治疗后6个月，在随机点尿样中测量uKim-1到尿肌酐排泄量。
结果：治疗前LN组显示uNGAL和uKIM-1水平较高（P值<0.001）。ROC分析表明，uNGAL在>59的水平具有95%的敏感性，100%的特异性，诊断LN的能力为AUC=0.996。而uKIM-1ROC显示，在>1.6的水平，它具有85%的灵敏度，80%的特异性，和AUC=0.919。治疗后uNGAL和uKIM水平显著降低(P值<0.001)。治疗前后尿路指标与其他临床指标无显著相关性,炎症，和狼疮性肾炎的血清学标志物。
结论：uNGAL，uKIM,uNGAL/Creat比率,和uKIM/Creat比值可作为狼疮性肾炎疾病活动性的预测因子和标志。要点•肾活检是目前诊断狼疮性肾炎的标准,并且没有一种尿生物标志物被完全认为具有反映活性或对治疗的反应的诊断能力。•However,根据当前研究的发现，uNGAL,uKIM,uNGAL/Creat比率,和uKIM/Creat比值显示出显著的诊断性能,是系统性红斑狼疮患者肾脏受累的有力指标,也是疾病活动的标志.
