Division of Rheumatology, Johns Hopkins University School of Medicine, 1830 East Monument Street, Baltimore, MD 21205, USA.
J Rheumatol. 2009 Oct;36(10):2224-30. doi: 10.3899/jrheum.081112. Epub 2009 Jul 31.
Renal biopsy is the "gold standard" to determine renal activity in systemic lupus erythematosus (SLE), but it is expensive, invasive, and carries risk. Osteoprotegerin (OPG) is produced by the heart, lungs, kidney, and bone. Monocyte chemoattractant protein-1 (MCP-1), a chemotactic cytokine, is involved in the progression of glomerular and tubulointerstitial injury. We investigated both urine OPG and MCP-1 as potential biomarkers for lupus nephritis.
Our subjects, 87 patients with SLE (88% women; 48% African American, 41% Caucasian, 11% other), mean age 44 years, were followed monthly to quarterly. Urinary OPG (pg/ml) and MCP-1 (pg/ml) were measured (Luminex MAP bead assay).
OPG concentrations were strongly associated with global disease activity and with both renal activity on a visual analog scale (VAS) (p = 0.0006) and renal disease activity descriptors of the SELENA SLEDAI, including hematuria (p = 0.001) and a positive anti-dsDNA (p = 0.013). MCP-1 was also associated with the renal VAS (p = 0.032), renal disease activity descriptors of SELENA SLEDAI, including hematuria (p = 0.027), and with a positive anti-dsDNA (p = 0.016). We also examined the relationship between the biomarkers and having a urine protein to creatinine ratio (pr/cr) > or = 0.5. Among patients with medium or high OPG, 46% had urine pr/cr > or = 0.5, compared to only 23% among those with low OPG (p = 0.032). The 2 biomarkers were strongly correlated with each other (Spearman correlation coefficient 0.77, p < 0.0001).
The lack of availability of urine biomarkers has hampered development of new therapies for lupus nephritis. Urine MCP-1 and OPG were both associated with measures of lupus renal disease activity. Medium or high levels of OPG were predictive of a urine protein/creatinine ratio of > or = 0.5. Further study, including longitudinal assessment and correlation with concurrent renal biopsies, is necessary before this assay can be used in the routine clinic setting.
肾活检是确定系统性红斑狼疮（SLE）肾脏活动的“金标准”，但它昂贵、有创且存在风险。骨保护素（OPG）由心脏、肺、肾脏和骨骼产生。单核细胞趋化蛋白-1（MCP-1）是一种趋化细胞因子，参与肾小球和肾小管间质损伤的进展。我们研究了尿液 OPG 和 MCP-1 作为狼疮肾炎的潜在生物标志物。
我们的研究对象是 87 名 SLE 患者（88%为女性；48%为非裔美国人，41%为白种人，11%为其他种族），平均年龄 44 岁，每月至每季度随访一次。测量尿液 OPG（pg/ml）和 MCP-1（pg/ml）（Luminex MAP 珠测定法）。
OPG 浓度与总体疾病活动度以及视觉模拟量表（VAS）上的肾脏活动度（p=0.0006）和 SELENA SLEDAI 的肾脏疾病活动描述符强烈相关，包括血尿（p=0.001）和抗 dsDNA 阳性（p=0.013）。MCP-1 也与肾脏 VAS（p=0.032）、SELENA SLEDAI 的肾脏疾病活动描述符相关，包括血尿（p=0.027）和抗 dsDNA 阳性（p=0.016）。我们还检查了生物标志物与尿蛋白/肌酐比（pr/cr）>或=0.5 的关系。在 OPG 中或高的患者中，46%的患者尿 pr/cr>或=0.5，而 OPG 低的患者中只有 23%（p=0.032）。这两个生物标志物与彼此呈强烈相关（Spearman 相关系数 0.77，p<0.0001）。
缺乏尿液生物标志物阻碍了狼疮肾炎新疗法的发展。尿 MCP-1 和 OPG 均与狼疮肾疾病活动度相关。中或高 OPG 水平可预测 pr/cr>或=0.5 的尿液蛋白/肌酐比值。在常规临床环境中使用该检测之前，需要进行进一步的研究，包括纵向评估和与同期肾活检的相关性。
