Nephrology Unit, Internal Medicine Department, Faculty of Medicine, Assiut University, Assiut, Egypt.
Nephrology Unit, Internal Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Clin Rheumatol. 2024 Jan;43(1):167-174. doi: 10.1007/s10067-023-06698-2. Epub 2023 Jul 29.
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.
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.
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.
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.
尽管已有大量关于狼疮肾炎的研究，但没有一种尿生物标志物被证明能够真正反映狼疮肾炎的活动、对治疗的反应或预后。我们旨在研究狼疮肾炎中的尿生物标志物，并检验其与肾脏损伤的关系。
40 名系统性红斑狼疮（SLE）患者被分为两组：（1）狼疮肾炎组，活检证实为增生性狼疮肾炎（III 级和 IV 级），且在过去 3 个月内除糖皮质激素外未接受免疫抑制剂治疗；（2）狼疮非肾炎组，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度。在肾活检时和诱导治疗后 6 个月，我们测量了随机尿样中的尿中性粒细胞明胶酶相关脂质运载蛋白（uNGAL）、尿肾损伤分子-1（uKim-1）、尿 NGAL 与尿肌酐排泄比值（mg/dl）和尿 Kim-1 与尿肌酐排泄比值。
治疗前狼疮肾炎组的 uNGAL 和 uKIM-1 水平更高（P 值<0.001）。ROC 分析显示，uNGAL 水平>59 时，诊断 LN 的灵敏度为 95%，特异性为 100%，AUC=0.996。而 uKIM-1 的 ROC 显示，当水平>1.6 时，其灵敏度为 85%，特异性为 80%，AUC=0.919。治疗后 uNGAL 和 uKIM 水平显著降低（P 值<0.001）。治疗前后尿标志物与狼疮肾炎的其他临床、炎症和血清学标志物之间无显著相关性。
uNGAL、uKIM、uNGAL/尿肌酐比值和 uKIM/尿肌酐比值可作为狼疮肾炎疾病活动的预测指标和标志物。关键点：• 肾活检是狼疮肾炎的现行诊断标准，目前尚无任何尿生物标志物被充分证明具有诊断效力，能够反映活动或对治疗的反应。• 然而，基于本研究的结果，uNGAL、uKIM、uNGAL/尿肌酐比值和 uKIM/尿肌酐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物。
