Department of Internal Medicine, Division of Nephrology and Transplantation, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Department of Biomedicine, Aarhus University, Aarhus, Denmark.
Curr Opin Nephrol Hypertens. 2022 Sep 1;31(5):464-470. doi: 10.1097/MNH.0000000000000822. Epub 2022 Jul 18.
To review recent developments in urinary extracellular vesicles (uEVs) to study kidney physiology and disease.
Proteomic analysis in rats showed significant correlations between kidney and uEV protein abundances. Consistent with uEV biogenesis, these correlations were stronger for membrane-associated proteins than for e.g. soluble kinases or E3 ubiquitin ligases. When challenged with a high potassium diet, the physiologically predicted protein changes occurred both in kidney and uEVs, suggesting that analysis of uEVs might be utilized as a proxy or even replacement for tissue analysis. Although kidney-uEV correlations are more difficult to obtain in humans, analysis of uEV cargo from patients with inherited tubulopathies or with primary aldosteronism were also consistent with the predicted changes at the tissue level. The kidney appears to be the main source of uEVs, with a recent study showing that nephron mass determines uEV excretion rate. Therefore, a measure of nephron mass should be included for between-subject comparisons.
The overall good correlation between kidney and uEV protein abundances renders uEVs an attractive noninvasive source of biomarkers for studying kidney physiology or disease. However, differences in per-protein kidney-uEV correlations and per-person uEV excretion rates should be considered in uEV biomarker studies.
综述尿细胞外囊泡（uEVs）在研究肾脏生理和疾病方面的最新进展。
在大鼠中的蛋白质组学分析表明肾脏和 uEV 蛋白丰度之间存在显著相关性。与 uEV 生物发生一致，这些相关性在膜相关蛋白中比可溶性激酶或 E3 泛素连接酶等更强。当用高钾饮食挑战时，在肾脏和 uEV 中都发生了生理上可预测的蛋白变化，这表明 uEV 的分析可作为组织分析的替代物甚至替代物。尽管在人类中更难获得肾脏-uEV 相关性，但对遗传性肾小管病变或原发性醛固酮增多症患者的 uEV 货物进行分析，与组织水平的预测变化也是一致的。肾脏似乎是 uEVs 的主要来源，最近的一项研究表明，肾小球滤过率决定了 uEV 的排泄率。因此，对于个体间的比较，应包括肾小球滤过率的测量。
肾脏和 uEV 蛋白丰度之间的总体良好相关性使得 uEVs 成为研究肾脏生理或疾病的有吸引力的非侵入性生物标志物来源。然而，在 uEV 生物标志物研究中，应考虑每个蛋白的肾脏-uEV 相关性和每个人的 uEV 排泄率的差异。
