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Assessment of Urinary Exosomal NHE3 as a Biomarker of Acute Kidney Injury
The diagnosis of acute kidney injury (AKI) traditionally depends on the serum creatinine (Scr) and urine output, which lack sufficient sensitivity and specificity. Using urinary exosomes as a biomarker has unique advantages. To assess whether urinary exosomal Na(+)/H(+) exchanger isoform 3 (NHE3) pr...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9689824/ https://www.ncbi.nlm.nih.gov/pubmed/36359477 http://dx.doi.org/10.3390/diagnostics12112634 |
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author | Yu, Yanting Ren, Zhiyun Xie, Anni Jia, Yutao Xue, Ying Wang, Ping Ji, Daxi Wang, Xiaoyan |
author_facet | Yu, Yanting Ren, Zhiyun Xie, Anni Jia, Yutao Xue, Ying Wang, Ping Ji, Daxi Wang, Xiaoyan |
author_sort | Yu, Yanting |
collection | PubMed |
description | The diagnosis of acute kidney injury (AKI) traditionally depends on the serum creatinine (Scr) and urine output, which lack sufficient sensitivity and specificity. Using urinary exosomes as a biomarker has unique advantages. To assess whether urinary exosomal Na(+)/H(+) exchanger isoform 3 (NHE3) protein could serve as a biomarker of AKI, we constructed four AKI rat models: cisplatin (7.5 mg/kg) injected intraperitoneally (IP), furosemide (20 mg/kg, IP) with a low-NaCl (0.03%) diet, a low-NaCl (0.03%) diet with candesartan (1 mg/kg, IP) and bilateral ischemia and reperfusion (I/R) injury for 40 min. Additionally, we assessed six sepsis-associated AKI patients and six healthy volunteers. Urinary exosomes were extracted by ultracentrifugation, and the NHE3 protein abundance was tested by immunoblotting for all the AKI rats and human subjects. The isolated cup-shaped particles with an average diameter of 70 nm and enrichment in CD63 were identified as exosomes. NHE3 abundance was six times higher in exosomes than in the whole urine. In cisplatin-induced AKI rats, urinary exosomal NHE3 was increased on day 2, one day earlier than the increases in Scr and blood urea nitrogen (BUN). In additional rats, urinary exosomal NHE3 decreased along with the decline in Scr after EPO pretreatment. In volume-depletion AKI induced by furosemide injection with a low-NaCl diet, the urinary exosomal NHE3 expression was higher than that in the control. Under a low-NaCl diet with candesartan-related AKI, the urinary exosomal NHE3 was elevated on day 5, earlier than Scr. In I/R-injury AKI, the urinary exosomal NHE3 was also raised compared with that in the control. In humans, the urinary exosomal NHE3 level was also elevated in sepsis-associated AKI patients in comparison with that in the healthy volunteers. The urinary exosomal NHE3 was increased in multiple AKI; it may be used as a diagnostic biomarker of AKI. |
format | Online Article Text |
id | pubmed-9689824 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96898242022-11-25 Assessment of Urinary Exosomal NHE3 as a Biomarker of Acute Kidney Injury Yu, Yanting Ren, Zhiyun Xie, Anni Jia, Yutao Xue, Ying Wang, Ping Ji, Daxi Wang, Xiaoyan Diagnostics (Basel) Article The diagnosis of acute kidney injury (AKI) traditionally depends on the serum creatinine (Scr) and urine output, which lack sufficient sensitivity and specificity. Using urinary exosomes as a biomarker has unique advantages. To assess whether urinary exosomal Na(+)/H(+) exchanger isoform 3 (NHE3) protein could serve as a biomarker of AKI, we constructed four AKI rat models: cisplatin (7.5 mg/kg) injected intraperitoneally (IP), furosemide (20 mg/kg, IP) with a low-NaCl (0.03%) diet, a low-NaCl (0.03%) diet with candesartan (1 mg/kg, IP) and bilateral ischemia and reperfusion (I/R) injury for 40 min. Additionally, we assessed six sepsis-associated AKI patients and six healthy volunteers. Urinary exosomes were extracted by ultracentrifugation, and the NHE3 protein abundance was tested by immunoblotting for all the AKI rats and human subjects. The isolated cup-shaped particles with an average diameter of 70 nm and enrichment in CD63 were identified as exosomes. NHE3 abundance was six times higher in exosomes than in the whole urine. In cisplatin-induced AKI rats, urinary exosomal NHE3 was increased on day 2, one day earlier than the increases in Scr and blood urea nitrogen (BUN). In additional rats, urinary exosomal NHE3 decreased along with the decline in Scr after EPO pretreatment. In volume-depletion AKI induced by furosemide injection with a low-NaCl diet, the urinary exosomal NHE3 expression was higher than that in the control. Under a low-NaCl diet with candesartan-related AKI, the urinary exosomal NHE3 was elevated on day 5, earlier than Scr. In I/R-injury AKI, the urinary exosomal NHE3 was also raised compared with that in the control. In humans, the urinary exosomal NHE3 level was also elevated in sepsis-associated AKI patients in comparison with that in the healthy volunteers. The urinary exosomal NHE3 was increased in multiple AKI; it may be used as a diagnostic biomarker of AKI. MDPI 2022-10-30 /pmc/articles/PMC9689824/ /pubmed/36359477 http://dx.doi.org/10.3390/diagnostics12112634 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Yu, Yanting Ren, Zhiyun Xie, Anni Jia, Yutao Xue, Ying Wang, Ping Ji, Daxi Wang, Xiaoyan Assessment of Urinary Exosomal NHE3 as a Biomarker of Acute Kidney Injury |
title | Assessment of Urinary Exosomal NHE3 as a Biomarker of Acute Kidney Injury |
title_full | Assessment of Urinary Exosomal NHE3 as a Biomarker of Acute Kidney Injury |
title_fullStr | Assessment of Urinary Exosomal NHE3 as a Biomarker of Acute Kidney Injury |
title_full_unstemmed | Assessment of Urinary Exosomal NHE3 as a Biomarker of Acute Kidney Injury |
title_short | Assessment of Urinary Exosomal NHE3 as a Biomarker of Acute Kidney Injury |
title_sort | assessment of urinary exosomal nhe3 as a biomarker of acute kidney injury |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9689824/ https://www.ncbi.nlm.nih.gov/pubmed/36359477 http://dx.doi.org/10.3390/diagnostics12112634 |
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