In the article by Lv et al.¹ published in the Journal of the American Society of Nephrology, the authors describe enhanced urinary exosomal release in experimental models of acute and chronic renal injury. They also describe increased exosomal release in patients with IgA nephropathy and a correlation between exosomal concentration and proteinuria. These findings are of clear interest, but we have reservations about some of the methodology used to ascertain this observation. They use nanoparticle tracking analysis (NTA) of urine and describe enhanced particle concentration in patients who are proteinuric. We have recently reported similar observations using NTA in 32 patients with varying levels of albuminuria.² We found that albuminuria confounded particle analysis by NTA, because albumin-containing solutions contain particles of exosome-like size, and such particles can mimic exosomes in standard NTA. Immunodepletion of albumin from proteinuric urine resulted in a substantial reduction in the concentration of particles detected by NTA as did urine purification using iodixanol density gradients. More importantly, NTA measurements of pure albumin solutions yielded a substantial number of particles with a diameter of 105 nm. This reinforces the need for great caution in the interpretation of NTA results in fluids that have significant levels of protein. It also emphasizes the importance of stringent methods of purification, such as density gradients, in exosome analysis as recommended by the International Society for Extracellular Vesicles.³

中文翻译：

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尿液检测外泌体的纳米颗粒追踪分析可能与白蛋白尿混淆

在吕等人的文章中。¹发表在《美国肾脏病学杂志》上，作者描述了在急性和慢性肾脏损伤的实验模型中尿液外泌体释放的增强。他们还描述了IgA肾病患者外泌体释放增加以及外泌体浓度与蛋白尿之间的相关性。这些发现引起了人们的兴趣，但我们对确定该观察结果所采用的某些方法持保留态度。他们使用尿液的纳米颗粒跟踪分析（NTA）并描述了蛋白尿患者的颗粒浓度增加。我们最近报道了使用NTA对32名蛋白尿水平不同的患者进行的类似观察。^2个我们发现白蛋白尿症混淆了NTA的颗粒分析，这是因为含白蛋白的溶液含有大小类似外泌体的颗粒，并且这种颗粒可以模拟标准NTA中的外泌体。从蛋白尿中清除白蛋白会导致NTA检测到的颗粒浓度大大降低，这与使用碘克沙醇密度梯度进行的尿液净化一样。更重要的是，纯净白蛋白溶液的NTA测量结果产生了大量直径为105 nm的颗粒。这就需要在对NTA结果产生的蛋白质含量很高的液体进行解释时要格外小心。它还强调了严格的纯化方法（如密度梯度）在国际细胞外囊泡学会建议的外泌体分析中的重要性。³