Nephron mass determines the excretion rate of urinary extracellular vesicles

Autor: Charles J. Blijdorp, Thomas A. Hartjes, Kuang‐Yu Wei, Martijn H. vanHeugten, Dominique M. Bovée, Ricardo P.J. Budde, Jacqueline van deWetering, Joost G.J. Hoenderop, Martin E. vanRoyen, Robert Zietse, David Severs, Ewout J. Hoorn
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Journal of Extracellular Vesicles, Vol 11, Iss 1, Pp n/a-n/a (2022)
Druh dokumentu: article
ISSN: 2001-3078
DOI: 10.1002/jev2.12181
Popis: Abstract Urinary extracellular vesicles (uEVs) are emerging as non‐invasive biomarkers for various kidney diseases, but it is unknown how differences in nephron mass impact uEV excretion. 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‐free spot and 24‐h urine samples using nanoparticle tracking analysis (NTA), EVQuant, and CD9‐time‐resolved 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‐h urine creatinine. Donor nephrectomy reduced eGFR by 36% ± 10%, but the excretion of uEVs by only 16% (CD9+ uEVs ‐37%, CD9‐ uEVs no decrease). Donor nephrectomy increased the podocyte marker WT‐1 and the proximal tubule markers NHE3, NaPi‐IIa, and cubilin in uEVs two‐ to four‐fold when correcting for the nephrectomy. In rats, the changes in GFR and kidney weight correlated with the changes in uEV excretion rate (R = 0.46 and 0.60, P
Databáze: Directory of Open Access Journals
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