Gupta R, Aggarwal A, Sinha S, Rajasekhar L, Yadav A, Gaur P, Misra R, Negi V S
Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
Lupus. 2016 Oct;25(11):1230-6. doi: 10.1177/0961203316636470. Epub 2016 Mar 1.
Urinary biomarkers may help in identification, treatment and assessment of response in patients with lupus nephritis (LN). Osteoprotegerin (OPG) is produced by the kidneys and lymphoid cells and may reflect renal disease activity better. The data on its utility are sparse.
Fifty-eight patients with active LN (AN), 24 with active non-renal disease (ANR) and 39 with inactive disease (ID) were included. Median disease duration was 32 (1-204) months and median age was 27 (12-50) years. AN patients were followed up every three months for one year. Urine and serum samples were collected for OPG measurement by ELISA (pg/ml) and urinary values were normalised for creatinine excretion (pg/mg). Urine samples from 24 healthy individuals (HCs) and 20 patients each of rheumatoid arthritis (RA) and diabetic nephropathy (DM) served as controls. Variables were expressed as median (range).
At baseline, normalised urinary OPG (uOPG) was significantly higher (p < 0.001) in AN (1229 (0-8577)) than ANR (236 (0-14713)), ID (463 (7-4253)), HCs (366 (120-2849)) and DM (350 (127-1577)) but it was not different from RA (1511 (122-8849)). uOPG correlated modestly with rSLEDAI (r = 0.4, p < 0.001) and SLEDAI (r = 0.31, p < 0.001) but not with serum OPG (sOPG). uOPG but not sOPG could differentiate between AN and ANR groups. In the longitudinal study, uOPG and sOPG decreased significantly with treatment at all follow-up visits but the trend of fall in sOPG was erratic. uOPG values at baseline, 3, 6, 9 and 12 months were 1229 (0-8577), 466 (3-4874), 104 (0-1598), 325 (0-4025) and 555 (6-6771) pg/mg, respectively. uOPG but not sOPG rose before conventional markers in three patients who had a relapse of LN. In two patients who developed chronic kidney disease, uOPG remained persistently high. For differentiating AN from ANR patients, uOPG performed the best on receiver operator characteristics analysis (AUC = 0.72) when compared with anti-dsDNA antibodies, C3, C4 and sOPG.
uOPG is derived from kidneys and helps differentiate active SLE patients with and without LN. It shows modest correlation with disease activity and has a potential to predict poor response to therapy and relapse of LN.
尿生物标志物可能有助于狼疮性肾炎（LN）患者的识别、治疗及反应评估。骨保护素（OPG）由肾脏和淋巴细胞产生，可能能更好地反映肾脏疾病活动情况。关于其效用的数据较少。
纳入58例活动性LN（AN）患者、24例活动性非肾脏疾病（ANR）患者和39例非活动性疾病（ID）患者。疾病持续时间中位数为32（1 - 204）个月，年龄中位数为27（12 - 50）岁。对AN患者随访1年，每3个月进行一次。收集尿液和血清样本，采用酶联免疫吸附测定法（ELISA）测量OPG（pg/ml），尿液值根据肌酐排泄量进行标准化（pg/mg）。来自24名健康个体（HCs）以及20例类风湿关节炎（RA）和糖尿病肾病（DM）患者的尿液样本作为对照。变量以中位数（范围）表示。
基线时，AN患者标准化尿OPG（uOPG）[1229（0 - 8577）]显著高于ANR患者[236（0 - 14713）]、ID患者[463（7 - 4253）]、HCs[366（120 - 2849）]和DM患者[350（127 - 1577）]（p < 0.001），但与RA患者[1511（122 - 8849）]无差异。uOPG与rSLEDAI（r = 0.4，p < 0.001）和SLEDAI（r = 0.31，p < 0.001）呈中度相关，但与血清OPG（sOPG）无关。uOPG而非sOPG能够区分AN组和ANR组。在纵向研究中，所有随访时uOPG和sOPG随治疗均显著下降，但sOPG下降趋势不稳定。基线、3、6、9和12个月时uOPG值分别为1229（0 - 8577）、466（3 - 4874）、104（0 - 1598）、325（0 - 4025）和555（6 - 6771）pg/mg。3例LN复发患者中，uOPG而非sOPG在传统标志物之前升高。2例发生慢性肾脏病的患者中，uOPG持续保持高水平。在区分AN与ANR患者方面，与抗双链DNA抗体、C3、C4和sOPG相比，uOPG在受试者工作特征分析中表现最佳（AUC = 0.72）。
uOPG源自肾脏，有助于区分有和无LN的活动性SLE患者。它与疾病活动呈中度相关，有预测LN治疗反应不佳和复发的潜力。
