Department of Rheumatology, Hospital de Santa Maria, Lisbon, Portugal.
Division of Allergy Immunology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Lupus Sci Med. 2022 Aug;9(1). doi: 10.1136/lupus-2022-000719.
Lupus nephritis is a key driver of morbidity and mortality in SLE. Detecting active nephritis on a background of pre-existing renal damage is difficult, leading to potential undertreatment and accumulating injury. An unmet need is a biomarker that distinguishes active lupus nephritis, particularly important in paediatrics where minimising invasive procedures is desirable.
This was a multicentre, prospective study of 113 paediatric patients with biopsy-proven lupus nephritis. Clinical data and urine were obtained every 3-4 months and patients averaged 2 years on study with seven time points. Urine was analysed for human epidermal growth factor receptor 2 (HER2), tumour necrosis factor-like weak inducer of apoptosis and vascular cell adhesion molecule-1 (VCAM-1) by ELISA. We defined active disease as either a rise in serum creatinine ≥0.3 mg/dL from baseline or a rise in renal Systemic Lupus Erythematosus Disease Activity Index score from the previous visit. These markers were also studied in patients with acute kidney injury, juvenile idiopathic arthritis (JIA), amplified pain syndrome and healthy controls.
The rate of active disease was 56% over an average of 2 years of follow-up. HER2 and VCAM-1 were significantly elevated at time points with active disease defined by increased serum creatinine compared with time points with inactive disease or patients who never flared. All three biomarkers were associated with new-onset proteinuria and VCAM-1 was elevated at time points preceding new-onset proteinuria. These biomarkers were not increased in acute kidney injury or JIA.
All three biomarkers were associated with new onset proteinuria and increased VCAM-1 may predict impending proteinuria. These biomarkers provide potential non-invasive measures for monitoring that may be more sensitive to impending flare than conventional measures.
狼疮肾炎是系统性红斑狼疮患者发病率和死亡率的主要驱动因素。在存在先前肾损伤的背景下检测活动性肾炎较为困难，这导致潜在的治疗不足和损伤累积。目前仍需要一种生物标志物来区分活动性狼疮肾炎，在儿科中这一点尤为重要，因为在儿科中，人们希望尽量减少侵入性操作。
这是一项多中心、前瞻性研究，纳入了 113 名经活检证实的狼疮肾炎儿科患者。每 3-4 个月采集临床数据和尿液，患者的平均研究时间为 2 年，共 7 个时间点。通过 ELISA 法分析尿液中人表皮生长因子受体 2（HER2）、肿瘤坏死因子样弱凋亡诱导因子和血管细胞黏附分子-1（VCAM-1）。我们将血清肌酐基线升高≥0.3mg/dL 或上次就诊时肾红斑狼疮疾病活动指数评分升高定义为疾病活动。还研究了这些标志物在急性肾损伤、幼年特发性关节炎（JIA）、放大疼痛综合征和健康对照组患者中的情况。
在平均 2 年的随访中，有 56%的患者出现活动性疾病。与无疾病活动或从未发作的患者相比，在血清肌酐升高定义为疾病活动的时间点，HER2 和 VCAM-1 显著升高。所有三种生物标志物均与新发性蛋白尿相关，且 VCAM-1 在新发性蛋白尿出现前的时间点升高。这些生物标志物在急性肾损伤或 JIA 中并未升高。
所有三种生物标志物均与新发性蛋白尿相关，且 VCAM-1 升高可能预示即将出现蛋白尿。与常规指标相比，这些生物标志物为监测提供了潜在的非侵入性指标，可能对即将出现的疾病活动更为敏感。
