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Nephron mass determines the excretion rate of urinary extracellular vesicles

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...

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Autores principales: Blijdorp, Charles J., Hartjes, Thomas A., Wei, Kuang‐Yu, van Heugten, Martijn H., Bovée, Dominique M., Budde, Ricardo P.J., van de Wetering, Jacqueline, Hoenderop, Joost G.J., van Royen, Martin E., Zietse, Robert, Severs, David, Hoorn, Ewout J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8783354/
https://www.ncbi.nlm.nih.gov/pubmed/35064766
http://dx.doi.org/10.1002/jev2.12181
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author Blijdorp, Charles J.
Hartjes, Thomas A.
Wei, Kuang‐Yu
van Heugten, Martijn H.
Bovée, Dominique M.
Budde, Ricardo P.J.
van de Wetering, Jacqueline
Hoenderop, Joost G.J.
van Royen, Martin E.
Zietse, Robert
Severs, David
Hoorn, Ewout J.
author_facet Blijdorp, Charles J.
Hartjes, Thomas A.
Wei, Kuang‐Yu
van Heugten, Martijn H.
Bovée, Dominique M.
Budde, Ricardo P.J.
van de Wetering, Jacqueline
Hoenderop, Joost G.J.
van Royen, Martin E.
Zietse, Robert
Severs, David
Hoorn, Ewout J.
author_sort Blijdorp, Charles J.
collection PubMed
description 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 < 0.01). Furthermore, the estimated degree of hypertrophy matched the change in uEV excretion rate (1.4‐ to 1.5‐fold after uninephrectomy and four‐fold after 5/6(th) 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.
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spelling pubmed-87833542022-02-01 Nephron mass determines the excretion rate of urinary extracellular vesicles Blijdorp, Charles J. Hartjes, Thomas A. Wei, Kuang‐Yu van Heugten, Martijn H. Bovée, Dominique M. Budde, Ricardo P.J. van de Wetering, Jacqueline Hoenderop, Joost G.J. van Royen, Martin E. Zietse, Robert Severs, David Hoorn, Ewout J. J Extracell Vesicles Research Articles 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 < 0.01). Furthermore, the estimated degree of hypertrophy matched the change in uEV excretion rate (1.4‐ to 1.5‐fold after uninephrectomy and four‐fold after 5/6(th) 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. John Wiley and Sons Inc. 2022-01-22 2022-01 /pmc/articles/PMC8783354/ /pubmed/35064766 http://dx.doi.org/10.1002/jev2.12181 Text en © 2021 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Blijdorp, Charles J.
Hartjes, Thomas A.
Wei, Kuang‐Yu
van Heugten, Martijn H.
Bovée, Dominique M.
Budde, Ricardo P.J.
van de Wetering, Jacqueline
Hoenderop, Joost G.J.
van Royen, Martin E.
Zietse, Robert
Severs, David
Hoorn, Ewout J.
Nephron mass determines the excretion rate of urinary extracellular vesicles
title Nephron mass determines the excretion rate of urinary extracellular vesicles
title_full Nephron mass determines the excretion rate of urinary extracellular vesicles
title_fullStr Nephron mass determines the excretion rate of urinary extracellular vesicles
title_full_unstemmed Nephron mass determines the excretion rate of urinary extracellular vesicles
title_short Nephron mass determines the excretion rate of urinary extracellular vesicles
title_sort nephron mass determines the excretion rate of urinary extracellular vesicles
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8783354/
https://www.ncbi.nlm.nih.gov/pubmed/35064766
http://dx.doi.org/10.1002/jev2.12181
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