Bharti Niharika, Rai Mohit Kumar, Singh Snigdha, Agarwal Vikas, Prasad Narayan, Pandey Rakesh, Agrawal Vinita
Departments of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India.
Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India.
Int Urol Nephrol. 2024 Mar;56(3):1071-1081. doi: 10.1007/s11255-023-03743-6. Epub 2023 Aug 24.
Endothelial injury, involved in the pathogenesis of renal fibrosis, can generate microparticles (MPs). These are 0.1-1 µm membrane-bound vesicles shed from the damaged or activated cell surfaces. We analyzed the presence of circulating MPs and EnMPs in IgAN and correlated with markers of endothelial injury and disease activity.
The study included 30 IgAN (mean age 31.5 ± 9 years), 25 healthy controls and Lupus nephritis (n = 10) as disease controls. Circulating MPs were quantitated by Flow cytometry and EnMPs were analyzed using anti-CD31-FITC and anti-CD146-PE antibodies. Their levels were correlated with serum von Willebrand Factor, histological Oxford MEST-C score and renal outcome. A prospective validation group of 20 patients of biopsy-proven IgA nephropathy was also included.
IgAN had significantly higher levels of MPs, EnMPs and vWF compared to controls. On multivariate analysis, plasma levels of total MPs, EnMPs and serum vWF correlated significantly with the presence of hypertension and E1 on histology. E1 and high MPs (> 130 counts/µl) were associated with shorter time to doubling of serum creatinine. MPs cutoff level of 130 counts/µl had a sensitivity of 75%, specificity of 93.3% and diagnostic accuracy of 89.5% for E1 in the validation cohort.
Circulating MPs and EnMPs in IgAN correlate with E1 on histology and have a potential as non-invasive biomarkers to predict disease activity and renal outcome.
内皮损伤参与肾纤维化的发病机制,可产生微粒(MPs)。这些是从受损或活化的细胞表面脱落的0.1 - 1微米的膜结合囊泡。我们分析了IgA肾病中循环MPs和内皮微粒(EnMPs)的存在情况,并将其与内皮损伤标志物和疾病活动度相关联。
该研究纳入了30例IgA肾病患者(平均年龄31.5±9岁)、25例健康对照者以及10例狼疮性肾炎患者作为疾病对照。通过流式细胞术对循环MPs进行定量分析,使用抗CD31 - FITC和抗CD146 - PE抗体分析EnMPs。它们的水平与血清血管性血友病因子、组织学牛津MEST-C评分及肾脏预后相关。还纳入了一个由20例经活检证实的IgA肾病患者组成的前瞻性验证组。
与对照组相比,IgA肾病患者的MPs、EnMPs和血管性血友病因子水平显著更高。多因素分析显示,总MPs、EnMPs的血浆水平以及血清血管性血友病因子与高血压的存在及组织学上的E1显著相关。E1和高MPs(>130个/微升)与血清肌酐翻倍时间缩短相关。在验证队列中,MPs截断水平为130个/微升时,对E1的敏感性为75%,特异性为93.3%,诊断准确性为89.5%。
IgA肾病中的循环MPs和EnMPs与组织学上的E1相关,具有作为预测疾病活动度和肾脏预后的非侵入性生物标志物的潜力。