Up to 70% of patients with ANCA-associated vasculitis (AAV) develop GN, with 26% progressing to ESKD. Diagnostic-grade and noninvasive tools to detect active renal inflammation are needed. Urinary soluble CD163 (usCD163) is a promising biomarker of active renal vasculitis, but a diagnostic-grade assay, assessment of its utility in prospective diagnosis of renal vasculitis flares, and evaluation of its utility in proteinuric states are needed.

We assessed a diagnostic-grade usCD163 assay in (1) a real-world cohort of 405 patients with AAV and 121 healthy and 488 non-AAV disease controls; (2) a prospective multicenter study of 84 patients with potential renal vasculitis flare; (3) a longitudinal multicenter cohort of 65 patients with podocytopathy; and (4) a cohort of 29 patients with AAV (with or without proteinuria) and ten controls.

We established a diagnostic reference range, with a cutoff of 250 ng/mmol for active renal vasculitis (area under the curve [AUC], 0.978). Using this cutoff, usCD163 was elevated in renal vasculitis flare (AUC, 0.95) but remained low in flare mimics, such as nonvasculitic AKI. usCD163’s specificity declined in patients with AAV who had nephrotic-range proteinuria and in those with primary podocytopathy, with 62% of patients with nephrotic syndrome displaying a "positive" usCD163. In patients with AAV and significant proteinuria, usCD163 normalization to total urine protein rather than creatinine provided the greatest clinical utility for diagnosing active renal vasculitis.

usCD163 is elevated in renal vasculitis flare and remains low in flare mimics. Nonspecific protein leakage in nephrotic syndrome elevates usCD163 in the absence of glomerular macrophage infiltration, resulting in false-positive results; this can be corrected with urine protein normalization.

高达 70% 的 ANCA 相关血管炎 (AAV) 患者会发展为 GN，其中 26% 会进展为 ESKD。需要诊断级和无创工具来检测活动性肾脏炎症。尿液可溶性 CD163 (usCD163) 是一种很有前途的活动性肾血管炎生物标志物，但需要进行诊断级测定、评估其在肾血管炎发作前瞻性诊断中的效用，以及评估其在蛋白尿状态下的效用。

我们在 ( 1 ) 一个由 405 名 AAV 患者和 121 名健康人和 488 名非 AAV 疾病对照者组成的真实世界队列中评估了诊断级 usCD163 测定；( 2 ) 一项针对 84 例潜在肾血管炎发作患者的前瞻性多中心研究；( 3 ) 65 例足细胞病患者的纵向多中心队列研究；( 4 ) 一组 29 名 AAV 患者（伴或不伴蛋白尿）和 10 名对照者。

我们建立了一个诊断参考范围，活动性肾血管炎的截止值为 250 ng/mmol（曲线下面积 [AUC]，0.978）。使用此截断值，usCD163 在肾血管炎发作 (AUC，0.95) 中升高，但在类似发作的情况下仍然很低，例如非血管炎性 AKI。usCD163 的特异性在患有肾病范围蛋白尿的 AAV 患者和原发性足细胞病患者中下降，62% 的肾病综合征患者显示 usCD163 呈“阳性”。在患有 AAV 和显着蛋白尿的患者中，usCD163 标准化为总尿蛋白而不是肌酐为诊断活动性肾血管炎提供了最大的临床效用。

usCD163 在肾血管炎发作时升高，而在发作模拟物中保持较低水平。在没有肾小球巨噬细胞浸润的情况下，肾病综合征的非特异性蛋白渗漏会升高 usCD163，导致假阳性结果；这可以通过尿蛋白正常化来纠正。