Exploring molecular pathology of chronic kidney disease in systemic sclerosis by analysis of urinary and serum proteins.
Exploring molecular pathology of chronic kidney disease in systemic sclerosis by analysis of urinary and serum proteins.
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DOI：
10.1093/rap/rkaa083
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发表时间：
2021
影响因子：
3.1
通讯作者：
Denton CP
中科院分区：
文献类型：
--
作者：
Stern EP;Unwin R;Burns A;Ong VH;Denton CP
累及肾脏常见于系统性硬化症（硬皮病，SSc），包括慢性肾脏疾病（CKD）。我们对尿蛋白进行了分析，以深入了解SSc中CKD的局部分子病理学，并确定用于临床试验的候选标记物。为了评估可能特异性反映SSc相关CKD的尿蛋白，招募了确诊SSc的患者，并根据有无CKD进行分层。对照组包括CKD患者和无SSc的健康志愿者。采用多重免疫分析法检测血清和尿液中候选标志物的il - 6、il - 18、TNF-α、单核细胞趋化蛋白1 （MCP1）、单核细胞趋化蛋白3 （MCP3）、VEGF及可溶性黏附分子血管细胞黏附分子1 （VCAM-1）和细胞间黏附分子1 （ICAM-1）。共检查了102名受试者，包括无CKD证据的SSc患者（n = 40）、伴有CKD的SSc患者（n = 39）、非SSc型CKD患者（n = 11）和健康志愿者（n = 12）。SSc患者尿中il - 6、MCP1、TNF-α、MCP3、il - 18和ICAM-1水平均高于健康对照组。最显著的差异是MCP1和ICAM-1（均P < 0.0001），这些分析结果也显示组间总体差异最显著（MCP1的P = 0.003， ICAM-1的P < 0.0001）。这些指标在SSc - ckd和肾功能正常的SSc之间呈趋势（MCP1, P = 0.0868）或显著差异（ICAM-1, P = 0.0134）。尿液中候选分子标记物的水平似乎比血清标记物更能反映SSc-CKD。MCP1和ICAM-1是SSc - ckd的有希望的分子标记物，可能是SSc肾脏累及的潜在生物标志物。这可能会在未来的前瞻性分析中进行探讨。
Renal involvement is common in systemic sclerosis (scleroderma; SSc) and includes chronic kidney disease (CKD). We have performed analysis of urinary proteins to gain insight into local molecular pathology of CKD in SSc and identify candidate markers for use in clinical trials. To evaluate urinary proteins that might specifically reflect SSc-related CKD, patients were recruited with confirmed SSc and stratified for the presence or absence of CKD. Controls included patients with CKD and no SSc, in addition to healthy volunteers. Candidate markers were measured in serum and urine by multiplex immunoassay testing for IL6, IL18, TNF-α, monocyte chemoattractant protein 1 (MCP1), monocyte chemoattractant protein 3 (MCP3), VEGF and the soluble adhesion molecules vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1). One hundred and two subjects were examined, including patients with SSc with no evidence of CKD (n = 40), SSc with CKD (n = 39), non-SSc CKD (n = 11) and healthy volunteers (n = 12). Urinary levels of IL6, MCP1, TNF-α, MCP3, IL18 and ICAM-1 were elevated in SSc patients compared with healthy controls. The most significant differences were for MCP1 and ICAM-1 (both P < 0.0001), and these analytes also showed the most significant differences between groups overall (P = 0.003 for MCP1 and P < 0.0001 for ICAM-1). These markers showed a trend (MCP1, P = 0.0868) or a significant difference (ICAM-1, P = 0.0134) between SSc–CKD and SSc with normal renal function. Urinary levels of candidate molecular markers appear to reflect SSc–CKD more than serum markers. MCP1 and ICAM-1 are promising molecular markers for SSc–CKD and might be potential biomarkers of SSc renal involvement. This might be explored in future prospective analyses.
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DOI：
10.1053/j.ajkd.2012.12.022
发表时间：
2013-07
期刊：
American journal of kidney diseases : the official journal of the National Kidney Foundation
影响因子：
--
作者：
McMahon GM;Waikar SS
通讯作者：
Waikar SS
影响因子：
1.6
作者：
Brugos, B.;Vincze, Z.;Zeher, M.
通讯作者：
Zeher, M.
影响因子：
5.5
作者：
Abignano, Giuseppina;Blagojevic, Jelena;Del Galdo, Francesco
通讯作者：
Del Galdo, Francesco
影响因子：
--
作者：
Carulli, MT;Ong, VH;Denton, CP
通讯作者：
Denton, CP
影响因子：
39.2
作者：
Levey, Andrew S.;Coresh, Josef;Van Lente, Frederick
通讯作者：
Van Lente, Frederick