Association of Wilms tumor-1 protein in urinary exosomes with kidney injury: a population-based cross-sectional study
ObjectiveLoss of Wilms tumor-1 (WT1) protein, a podocytopathy marker, through urine exosome (uE), could be an early indication of kidney injury. We examined WT1 in uE (uE-WT1), along with other urine markers of glomerular and kidney tubule injury, in individuals without chronic kidney disease (CKD)....
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2023.1220309/full |
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| author | Sukhanshi Khandpur Medha Srivastava Rajni Sharma Shafaque Asif Dharmendra S. Bhadauria Prabhaker Mishra Anil J. Purty Swasti Tiwari |
| author_facet | Sukhanshi Khandpur Medha Srivastava Rajni Sharma Shafaque Asif Dharmendra S. Bhadauria Prabhaker Mishra Anil J. Purty Swasti Tiwari |
| author_sort | Sukhanshi Khandpur |
| collection | DOAJ |
| description | ObjectiveLoss of Wilms tumor-1 (WT1) protein, a podocytopathy marker, through urine exosome (uE), could be an early indication of kidney injury. We examined WT1 in uE (uE-WT1), along with other urine markers of glomerular and kidney tubule injury, in individuals without chronic kidney disease (CKD).MethodologyThe cross-sectional study included individuals who reported having no evidence of chronic kidney disease (CKD). Albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) were used to assess kidney function. eGFR was calculated using the 2009 CKD-EPI (CKD-Epidemiological) equation. WT1 was analyzed in uE from humans and Wistar rats (before and after the 9th week of diabetes, n = 20). uE-WT1, urinary neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) were estimated using ELISA. The Kruskal-Wallis H test, Mann-Whitney U test, and stepwise multivariable linear regression were performed.ResultsUrine NGAL and ACR increase with uE-WT1 quartiles (n = 146/quarter). Similarly, uE-WT1, KIM-1, and NGAL were positively associated with ACR. Furthermore, KIM-1, NGAL, and uE-WT1 correlated with ACR. uE-WT1 outperformed KMI-1 and NGAL to explain ACR variability (25% vs. 6% or 9%, respectively). Kidney injury in streptozotocin-induced diabetic rats was associated with a significant rise in uE-WT1. Moreover, the findings were confirmed by the histopathology of kidney tissues from rats.ConclusionuE-WT1 was strongly associated with kidney function in rats. In individuals without CKD, uE-WT1 outperformed NGAL as a determinant of differences in ACR. |
| first_indexed | 2024-03-11T23:50:08Z |
| format | Article |
| id | doaj.art-5b9fb513178648faa1d5ff31d644ece7 |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-03-11T23:50:08Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-5b9fb513178648faa1d5ff31d644ece72023-09-19T07:42:13ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2023-09-011010.3389/fmed.2023.12203091220309Association of Wilms tumor-1 protein in urinary exosomes with kidney injury: a population-based cross-sectional studySukhanshi Khandpur0Medha Srivastava1Rajni Sharma2Shafaque Asif3Dharmendra S. Bhadauria4Prabhaker Mishra5Anil J. Purty6Swasti Tiwari7Department of Molecular Medicine and Biotechnology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, IndiaDepartment of Molecular Medicine and Biotechnology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, IndiaDepartment of Molecular Medicine and Biotechnology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, IndiaDepartment of Molecular Medicine and Biotechnology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, IndiaDepartment of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, IndiaDepartment of Biostatistics and Health Informatics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, IndiaDepartment of Community Medicine, Pondicherry Institute of Medical Sciences (A Unit of Madras Medical Mission), Puducherry, IndiaDepartment of Molecular Medicine and Biotechnology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, IndiaObjectiveLoss of Wilms tumor-1 (WT1) protein, a podocytopathy marker, through urine exosome (uE), could be an early indication of kidney injury. We examined WT1 in uE (uE-WT1), along with other urine markers of glomerular and kidney tubule injury, in individuals without chronic kidney disease (CKD).MethodologyThe cross-sectional study included individuals who reported having no evidence of chronic kidney disease (CKD). Albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) were used to assess kidney function. eGFR was calculated using the 2009 CKD-EPI (CKD-Epidemiological) equation. WT1 was analyzed in uE from humans and Wistar rats (before and after the 9th week of diabetes, n = 20). uE-WT1, urinary neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) were estimated using ELISA. The Kruskal-Wallis H test, Mann-Whitney U test, and stepwise multivariable linear regression were performed.ResultsUrine NGAL and ACR increase with uE-WT1 quartiles (n = 146/quarter). Similarly, uE-WT1, KIM-1, and NGAL were positively associated with ACR. Furthermore, KIM-1, NGAL, and uE-WT1 correlated with ACR. uE-WT1 outperformed KMI-1 and NGAL to explain ACR variability (25% vs. 6% or 9%, respectively). Kidney injury in streptozotocin-induced diabetic rats was associated with a significant rise in uE-WT1. Moreover, the findings were confirmed by the histopathology of kidney tissues from rats.ConclusionuE-WT1 was strongly associated with kidney function in rats. In individuals without CKD, uE-WT1 outperformed NGAL as a determinant of differences in ACR.https://www.frontiersin.org/articles/10.3389/fmed.2023.1220309/fullnon-invasivechronic kidney diseaseKIM-1NGALexosomesuE-WT1 |
| spellingShingle | Sukhanshi Khandpur Medha Srivastava Rajni Sharma Shafaque Asif Dharmendra S. Bhadauria Prabhaker Mishra Anil J. Purty Swasti Tiwari Association of Wilms tumor-1 protein in urinary exosomes with kidney injury: a population-based cross-sectional study Frontiers in Medicine non-invasive chronic kidney disease KIM-1 NGAL exosomes uE-WT1 |
| title | Association of Wilms tumor-1 protein in urinary exosomes with kidney injury: a population-based cross-sectional study |
| title_full | Association of Wilms tumor-1 protein in urinary exosomes with kidney injury: a population-based cross-sectional study |
| title_fullStr | Association of Wilms tumor-1 protein in urinary exosomes with kidney injury: a population-based cross-sectional study |
| title_full_unstemmed | Association of Wilms tumor-1 protein in urinary exosomes with kidney injury: a population-based cross-sectional study |
| title_short | Association of Wilms tumor-1 protein in urinary exosomes with kidney injury: a population-based cross-sectional study |
| title_sort | association of wilms tumor 1 protein in urinary exosomes with kidney injury a population based cross sectional study |
| topic | non-invasive chronic kidney disease KIM-1 NGAL exosomes uE-WT1 |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2023.1220309/full |
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