Assessment of urinary microparticles in normotensive patients with type 1 diabetes

Assessment of urinary microparticles in normotensive patients with type 1 diabetes
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DOI:
10.1007/s00125-016-4190-2
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发表时间:
2017-03-01
期刊:
影响因子:
8.2
通讯作者:
Burger, Dylan
Burger, Dylan
中科院分区:
医学1区
文献类型:
--
作者:
Lytvyn, Yuliya;Xiao, Fengxia;Burger, Dylan

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目的/假设评估尿细胞外囊泡,包括外来体和微粒(MP)是一种新兴的方法,用于非侵入性检测肾损伤。我们以前曾报道过糖尿病小鼠足细胞衍生的MP在蛋白尿之前增加。在这里,我们假设,1型糖尿病和急性高脂血症会增加尿足细胞MP水平在uncomplicateddiabetes.Methods在这事后探索性分析,我们检查存档的尿液样本正常白蛋白尿的患者与uncomplicated 1型糖尿病研究下钳夹正常白蛋白血症和高脂血症,并与健康对照组相比。尿囊进行了评估,电子显微镜和纳米粒子跟踪,而足细胞MP进行了评估,通过流式细胞术。结果无论是囊泡的大小,也不总数显着改变1型糖尿病或急性高血糖症。相比之下,1型糖尿病患者尿足细胞MP水平更高(0.47 [0.00-3.42] MP/μ mol肌酐[Cr])与健康对照相比(0.00 [0.00-0.00] MP/μ mol Cr,p < 0.05),在高血容量钳夹下增加(正常血容量期间为0.36 [0.00-4.15] MP/μ mol Cr,高血容量期间为2.70 [0.00-15.91] MP/μ mol Cr,p < 0.05)。尿白蛋白肌酐比和nephrin(足细胞损伤的替代品)的水平是不变的1型糖尿病或急性hyperglycemia.Conclusion/interprelation两者合计,我们的数据表明,尿足细胞MP水平较高的1型糖尿病患者在其他生物标志物(白蛋白尿,nephrin)的变化之前。足细胞MP的检查可以作为无并发症的1型糖尿病肾小球损伤的早期生物标志物。
Aims/hypothesis Assessment of urinary extracellular vesicles including exosomes and microparticles (MPs) is an emerging approach for non-invasive detection of renal injury. We have previously reported that podocyte-derived MPs are increased in diabetic mice in advance of albuminuria. Here, we hypothesised that type 1 diabetes and acute hyperglycaemia would increase urinary podocyte MP levels in uncomplicated diabetes.Methods In this post hoc exploratory analysis, we examined archived urine samples from normoalbuminuric patients with uncomplicated type 1 diabetes studied under clamped euglycaemia and hyperglycaemia and compared with healthy controls. Urinary vesicles were assessed by electron microscopy and nanoparticle tracking while podocyte MPs were assessed by flow cytometry.Results Neither vesicle size nor total number were significantly altered in type 1 diabetes or acute hyperglycaemia. By contrast, urinary podocyte MP levels were higher in type 1 diabetes (0.47 [0.00-3.42] MPs/mu mol creatinine [Cr]) compared with healthy controls (0.00 [0.00-0.00] MPs/mu mol Cr, p < 0.05) and increased under hyperglycaemic clamp (0.36 [0.00-4.15] MPs/mu mol Cr during euglycaemia vs 2.70 [0.00-15.91] MPs/mu mol Cr during hyperglycaemia, p < 0.05). Levels of urinary albumin to creatinine ratio and nephrin (surrogates of podocyte injury) were unchanged by type 1 diabetes or acute hyperglycaemia.Conclusion/interprelation Taken together, our data show that urinary podocyte MP levels are higher in patients with type 1 diabetes in advance of changes in other biomarkers (albuminuria, nephrin). Examination of podocyte MPs may serve as an early biomarker of glomerular injury in uncomplicated type 1 diabetes.