Raised Plasma Levels of Asymmetric Dimethylarginine Are Associated with Pathological Type and Predict the Therapeutic Effect in Lupus Nephritis Patients Treated with Cyclophosphamide.
Raised Plasma Levels of Asymmetric Dimethylarginine Are Associated with Pathological Type and Predict the Therapeutic Effect in Lupus Nephritis Patients Treated with Cyclophosphamide.
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不对称二甲基精氨酸血浆水平升高与病理类型相关，并可预测接受环磷酰胺治疗的狼疮肾炎患者的治疗效果。
DOI：
10.1159/000509767
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Yu Xueqing
中科院分区：
文献类型：
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作者：
Zhang Li;Zhang Kaichong;Dong Wei;Li Ruizhao;Huang Renwei;Zhang Hong;Shi Wanxin;Liu Shuangxin;Li Zhuo;Chen Yuanhan;Ye Zhiming;Liang Xinling;Yu Xueqing
狼疮性肾炎(LN)是系统性红斑狼疮(SLE)最严重的并发症之一。不对称二甲基精氨酸(ADMA)与SLE患者的心血管事件有关，是慢性肾脏疾病进展的有力预测指标。然而，ADMA是否能为LN患者的诊断和治疗提供预测价值仍不清楚。方法收集114例LN患者、52例原发性肾小球疾病患者和20例健康人的血液标本。采用酶联免疫吸附试验检测血浆ADMA水平。结果LN患者血浆ADMA水平与原发性肾小球疾病患者无明显差异，但均显著高于正常人(p<；0.05)。LN患者血浆ADMA水平与基础肾小球滤过率和血清超氧化物歧化酶呈负相关，与血清胱抑素C和血清β-2微球蛋白呈正相关(p<；0.05)。弥漫性增生期LN患者血浆ADMA水平显著高于其他病理类型LN患者。LN患者血浆ADMA水平升高(OR=1.012；95%CI为1.003~1.022；P=0.010)是弥漫性增生性LN的危险因素。血浆ADMA诊断弥漫性增生性LN的受试者工作特征曲线下面积为0.707(95%CI 0.610~0.805)。弥漫性增生期LN患者的ROC曲线下面积为0.796(95%CI为0.713~0.879)，显著高于ADMA、补体C3和EGFR的ROC曲线下面积。低水平血浆ADMA是环磷酰胺诱导治疗后增生性LN患者获得完全缓解的独立保护因素(OR=0.978；95%CI 0.961~0.996；P<；0.05)。低血浆ADMA水平有助于预测环磷酰胺诱导治疗的增生期LN患者的完全缓解。血浆ADMA可能成为判断LN病理类型和预测疗效的新的生物标志物。
BackgroundLupus nephritis (LN) is one of the most serious complications of systemic lupus erythematosus (SLE). Asymmetric dimethylarginine (ADMA) has been associated with cardiovascular events in SLE patients and is a strong predictor of the progression of chronic kidney disease. However, whether ADMA can provide a predictive value for the diagnosis and treatment of LN patients remains unclear. This study evaluated the clinical significance of ADMA in LN patients.MethodsBlood samples of 114 patients with LN, 52 patients with primary glomerular disease, and 20 healthy people were collected. Plasma ADMA was measured via enzyme-linked immunosorbent assay. The relationship between plasma ADMA levels and pathological types and renal function and efficacy in LN patients were further analyzed.ResultsThere was no significant difference in plasma ADMA levels between LN and primary glomerular disease, but both were significantly higher than the values in healthy people (p< 0.05). Plasma ADMA levels in LN patients were negatively correlated with baseline estimated glomerular filtration rate (eGFR) and serum superoxide dismutase and positively correlated with serum cystatin C and serum β 2-microglobulin (p< 0.05). The plasma ADMA levels of diffuse proliferative LN patients were significantly higher than those of other histopathological classes of LN. High plasma ADMA levels in LN patients (OR= 1.012; 95% CI 1.003–1.022; p= 0.010) is a risk factor for diffuse proliferative LN. The area under the receiver operating characteristic (ROC) curve of diagnosing diffuse proliferative LN by plasma ADMA was 0.707 (95% CI 0.610–0.805). The area under the ROC curve of combination with plasma ADMA, serum complement C3, and eGFR for diffuse proliferative LN was 0.796 (95% CI 0.713–0.879), which was significantly higher than that of ADMA, complement C3, and eGFR for diffuse proliferative LN alone, respectively (p< 0.05). Low plasma ADMA is an independent protective factor for proliferative LN patients achieving complete remission with cyclophosphamide as induction therapy (OR= 0.978; 95% CI 0.961–0.996; p< 0.05).ConclusionHigh plasma ADMA levels in combination with eGFR and complement C3 may be useful to diagnose diffuse proliferative LN. Low plasma ADMA may help to predict complete remission in proliferative LN patients treated with cyclophosphamide as induction therapy. Plasma ADMA may be a new biomarker to determine the pathological type of LN and predict the therapeutic effect.