Association of Wilms tumor-1 protein in urinary exosomes with kidney injury: a population-based cross-sectional study

Frontiers in Medicine

Medicine

Prabhaker Mishra¹  Anil J. Purty²  Swasti Tiwari³  Medha Srivastava³  Shafaque Asif³  Rajni Sharma³  Sukhanshi Khandpur³  Dharmendra S. Bhadauria⁴ 

[1] Department of Biostatistics and Health Informatics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India;Department of Community Medicine, Pondicherry Institute of Medical Sciences (A Unit of Madras Medical Mission), Puducherry, India;Department of Molecular Medicine and Biotechnology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India;Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India;

关键词: non-invasive;    chronic kidney disease;    KIM-1;    NGAL;    exosomes;    uE-WT1;   

DOI  :  10.3389/fmed.2023.1220309

 received in 2023-05-10, accepted in 2023-08-25,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

Unknown   
Copyright © 2023 Khandpur, Srivastava, Sharma, Asif, Bhadauria, Mishra, Purty and Tiwari.