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To address this, uEV excretion was measured before and after human kidney donor nephrectomy and rat nephrectomy. In male and female donors, uEVs were quantified in cell\u2010free spot and 24\u2010h urine samples using nanoparticle tracking analysis (NTA), EVQuant, and CD9\u2010time\u2010resolved fluorescence immunoassay. Female donors had significantly lower total kidney volume (TKV) and excreted 49% fewer uEVs than male donors. uEV excretion correlated positively with estimated glomerular filtration rate (eGFR), creatinine clearance, and TKV (R's between 0.6 and 0.7). uEV excretion rate could also be predicted from spot urines after multiplying spot uEV\/creatinine by 24\u2010h urine creatinine. Donor nephrectomy reduced eGFR by 36% \u00b1 10%, but the excretion of uEVs by only 16% (CD9+ uEVs \u201037%, CD9\u2010 uEVs no decrease). Donor nephrectomy increased the podocyte marker WT\u20101 and the proximal tubule markers NHE3, NaPi\u2010IIa, and cubilin in uEVs two\u2010 to four\u2010fold when correcting for the nephrectomy. In rats, the changes in GFR and kidney weight correlated with the changes in uEV excretion rate (<jats:italic>R<\/jats:italic>\u00a0=\u00a00.46 and 0.60, <jats:italic>P\u00a0<\/jats:italic>&lt;\u00a00.01). Furthermore, the estimated degree of hypertrophy matched the change in uEV excretion rate (1.4\u2010 to 1.5\u2010fold after uninephrectomy and four\u2010fold after 5\/6<jats:sup>th<\/jats:sup> nephrectomy). Taken together, our data show that uEV excretion depends on nephron mass, and that nephrectomy reduces uEV excretion less than expected based on nephron loss due to compensatory hypertrophy. The major implication of our findings is that a measure for nephron mass or uEV excretion rate should be included when comparing uEV biomarkers between individuals.<\/jats:p>","DOI":"10.1002\/jev2.12181","type":"journal-article","created":{"date-parts":[[2022,1,22]],"date-time":"2022-01-22T05:40:37Z","timestamp":1642830037000},"source":"Crossref","is-referenced-by-count":58,"title":["Nephron mass determines the excretion rate of urinary extracellular vesicles"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1449-4964","authenticated-orcid":false,"given":"Charles J.","family":"Blijdorp","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology and Transplantation Erasmus MC, University Medical Center Rotterdam  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A.","family":"Hartjes","sequence":"additional","affiliation":[{"name":"Department of Pathology Erasmus Medical Center, University Medical Center Rotterdam  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuang\u2010Yu","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology and Transplantation Erasmus MC, University Medical Center Rotterdam  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martijn H.","family":"van Heugten","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology and Transplantation Erasmus MC, University Medical Center Rotterdam  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique M.","family":"Bov\u00e9e","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology and Transplantation Erasmus MC, University Medical Center Rotterdam  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo P.J.","family":"Budde","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine Erasmus Medical Center, University Medical Center Rotterdam  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"van de Wetering","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology and Transplantation Erasmus MC, University Medical Center Rotterdam  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joost G.J.","family":"Hoenderop","sequence":"additional","affiliation":[{"name":"Department of Physiology Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin E.","family":"van Royen","sequence":"additional","affiliation":[{"name":"Department of Pathology Erasmus Medical Center, University Medical Center Rotterdam  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Zietse","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology and Transplantation Erasmus MC, University Medical Center Rotterdam  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Severs","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology and Transplantation Erasmus MC, University Medical Center Rotterdam  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8738-3571","authenticated-orcid":false,"given":"Ewout J.","family":"Hoorn","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology and Transplantation Erasmus MC, University Medical Center Rotterdam 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