Li Xiufeng, Liu Na, Liu Tianci, Liang Guowei, Shao Changgang, Ma Teng, Zhang Man
Aerospace Center Hospital, Department of Clinical Laboratory, Beijing, China.
Peking University Ninth School of Clinical Medicine, Beijing, China.
BMC Nephrol. 2025 Sep 26;26(1):530. doi: 10.1186/s12882-025-04457-w.
Atherosclerotic renal artery stenosis (ARAS) represents the predominant etiology of renal artery stenosis. Current diagnostic modalities—including renal arteriography, Doppler ultrasonography (DUS), computed tomography angiography (CTA), and magnetic resonance angiography (MRA)—are limited by invasiveness or technical constraints. The development of noninvasive biomarkers for ARAS detection is therefore clinically imperative. We hypothesize that ischemic renal injury in ARAS induces pathological alterations that generate unique urinary protein signatures.
A total of 138 subjects were enrolled and randomly divided into the discovery cohort and the validation cohort. Urinary proteins from the discovery cohort were profiled using data-independent acquisition mass spectrometry (DIA-MS) to identify differentially expressed proteins. Candidate biomarkers were subsequently validated in the validation cohort via quantitative ELISA. Diagnostic performance was assessed by receiver operating characteristic (ROC) curve analysis, and associations between target protein levels and clinical parameters were evaluated using Spearman correlation.
As a result of DIA-MS indicated in the discovery cohort, 485 up-regulated urinary proteins and 177 down-regulated urinary proteins were identified in ARAS patients compared to disease controls. The top three proteins CA3, ORM2, and ART3 in AUC were selected as the potential urinary markers for further validation in the validation cohort. The uCA3/Cr level was significantly higher in both ARAS and disease controls than in healthy controls, and the uCA3/Cr level in patients with ARAS was significantly higher than in disease controls. There was no statistical difference in the uCA3/Cr level in subgroups with different severity of ARAS. Taking healthy controls as control values, the ROC area of uCA3/Cr was 0.9649(95%CI: 0.9200-1.000). We evaluated the area under the uCA3/Cr curve with the values of the disease control group as the control, the areas of ROC were 0.7391(95%CI: 0.6154–0.8628). Correlation analysis demonstrated that there was a strong positive correlation between uCA3/Cr concentration and urinary a1-microglobulin(a1MG) in ARAS and disease controls.
CA3 in urine may be related to renal interstitial injury, it could be used as a non-invasive biomarker for ARAS. However, large cohort studies and mechanistic investigations are required for further validation.
The online version contains supplementary material available at 10.1186/s12882-025-04457-w.
动脉粥样硬化性肾动脉狭窄（ARAS）是肾动脉狭窄的主要病因。目前的诊断方法，包括肾动脉造影、多普勒超声检查（DUS）、计算机断层血管造影（CTA）和磁共振血管造影（MRA），都受到侵入性或技术限制。因此，开发用于ARAS检测的非侵入性生物标志物在临床上势在必行。我们假设ARAS中的缺血性肾损伤会引起病理改变，从而产生独特的尿蛋白特征。
共纳入138名受试者，并随机分为发现队列和验证队列。使用数据非依赖采集质谱法（DIA-MS）对发现队列中的尿蛋白进行分析，以鉴定差异表达的蛋白质。随后通过定量ELISA在验证队列中对候选生物标志物进行验证。通过受试者操作特征（ROC）曲线分析评估诊断性能，并使用Spearman相关性评估目标蛋白水平与临床参数之间的关联。
发现队列中DIA-MS的结果显示，与疾病对照组相比，ARAS患者中鉴定出485种上调的尿蛋白和177种下调的尿蛋白。选择AUC中排名前三的蛋白质CA3、ORM2和ART3作为潜在的尿标志物，在验证队列中进行进一步验证。ARAS组和疾病对照组的尿CA3/Cr水平均显著高于健康对照组，且ARAS患者的尿CA3/Cr水平显著高于疾病对照组。不同ARAS严重程度亚组的尿CA3/Cr水平无统计学差异。以健康对照组为对照值，尿CA3/Cr的ROC曲线下面积为0.9649（95%CI：0.9200-1.000）。以疾病对照组的值为对照评估尿CA3/Cr曲线下面积，ROC曲线下面积为0.7391（95%CI：0.6154-0.8628）。相关性分析表明，ARAS组和疾病对照组中尿CA3/Cr浓度与尿α1-微球蛋白（α1MG）之间存在强正相关。
尿CA3可能与肾间质损伤有关，可作为ARAS的非侵入性生物标志物。然而，需要进一步的大样本队列研究和机制研究来进行验证。
在线版本包含可在10.1186/s12882-025-04457-w上获取的补充材料。
