Trinity Health Kidney Centre, Trinity College Dublin, Dublin, Ireland.
Section of Rheumatology, Boston University School of Medicine, Boston, MA, USA.
Nephrol Dial Transplant. 2020 Feb 1;35(2):283-291. doi: 10.1093/ndt/gfy300.
Prior work has shown that urinary soluble CD163 (usCD163) displays excellent biomarker characteristics for detection of active renal vasculitis using samples that included new diagnoses with highly active renal disease. This study focused on the use of usCD163 in the detection of the more clinically relevant state of mild renal flare and compared results of usCD163 testing directly to testing of urinary monocyte chemoattractant protein-1 (uMCP-1).
Patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV, n = 88) were identified within a serially sampled, longitudinal and multicentre cohort. Creatinine-normalized usCD163 and uMCP-1 levels were measured by enzyme-linked immunosorbent assay and, both alone and in combination, were compared between times of active renal AAV and during remission and/or active non-renal AAV.
Samples from 320 study visits included times of active renal vasculitis (n = 39), remission (n = 233) and active extrarenal vasculitis (n = 48). Median creatinine levels were 0.9 mg/dL [interquartile range (IQR) 0.8-1.2] in remission and 1.4 mg/dL (IQR 1.0-1.8) during renal flare. usCD163 levels were higher in patients with active renal vasculitis compared with patients in remission and those with active extrarenal vasculitis, with median values of 162 ng/mmol (IQR 79-337), 44 (17-104) and 38 (7-76), respectively (P < 0.001). uMCP-1 levels were also higher in patients with active renal vasculitis compared with patients in remission and those with active extrarenal vasculitis, with median values of 10.6 pg/mmol (IQR 4.6-23.5), 4.1 (2.5-8.4) and 4.1 (1.9-6.8), respectively (P < 0.001). The proposed diagnostic cut-points for usCD163 and uMCP-1 were 72.9 ng/mmol and 10.0 pg/mmol, respectively. usCD163 and uMCP-1 levels were marginally correlated (r2 = 0.11, P < 0.001). Combining novel and existing biomarkers using recursive tree partitioning indicated that elevated usCD163 plus either elevated uMCP-1 or new/worse proteinuria improved the positive likelihood ratio (PLR) of active renal vasculitis to 19.2.
A combination of usCD163 and uMCP-1 measurements appears to be useful in identifying the diagnosis of subtle renal vasculitis flare.
先前的研究表明，尿可溶性 CD163（usCD163）在检测新诊断的伴有高度活跃性肾脏疾病的活动性肾脏血管炎时，显示出出色的生物标志物特征。本研究重点关注 usCD163 在检测更具临床相关性的轻度肾脏发作状态中的应用，并将 usCD163 检测的结果与尿单核细胞趋化蛋白-1（uMCP-1）的检测结果直接进行比较。
在一个连续采样的、纵向和多中心队列中，鉴定了抗中性粒细胞胞质抗体（ANCA）相关性血管炎（AAV，n=88）患者。通过酶联免疫吸附试验测量肌酐归一化的 usCD163 和 uMCP-1 水平，分别比较活动期肾脏 AAV 与缓解期和/或活动期非肾脏 AAV 时的单独和联合检测结果。
320 次研究访问的样本包括活动期肾脏血管炎（n=39）、缓解期（n=233）和活动期非肾脏血管炎（n=48）。缓解期肌酐中位数为 0.9mg/dL [四分位距（IQR）0.8-1.2]，肾血管炎发作期为 1.4mg/dL（IQR 1.0-1.8）。与缓解期和活动期非肾脏血管炎患者相比，活动期肾脏血管炎患者的 usCD163 水平更高，中位数分别为 162ng/mmol（IQR 79-337）、44（17-104）和 38（7-76）（P<0.001）。与缓解期和活动期非肾脏血管炎患者相比，活动期肾脏血管炎患者的 uMCP-1 水平也更高，中位数分别为 10.6pg/mmol（IQR 4.6-23.5）、4.1（2.5-8.4）和 4.1（1.9-6.8）（P<0.001）。usCD163 和 uMCP-1 的建议诊断截断值分别为 72.9ng/mmol 和 10.0pg/mmol。usCD163 和 uMCP-1 水平呈轻度相关（r2=0.11，P<0.001）。使用递归树分割对新型和现有生物标志物进行联合分析表明，升高的 usCD163 加上升高的 uMCP-1 或新出现/更严重的蛋白尿可将活动期肾脏血管炎的阳性似然比（PLR）提高至 19.2。
usCD163 和 uMCP-1 联合检测似乎可用于识别隐匿性肾脏血管炎发作。
