Wnt4 is a novel biomarker for the early detection of kidney tubular injury after ischemia/reperfusion injury.
Earlier intervention after acute kidney injury would promote better outcomes. Our previous study found that Wnt proteins are promptly upregulated after ischemic kidney injury. Thus, we assessed whether Wnt4 could be an early and sensitive biomarker of tubular injury. We subjected mice to bilateral ischemia/reperfusion injury (IRI). Kidney and urinary Wnt4 expression showed an early increase at 3 hours and increased further at 24 hours post-IRI and was closely correlated with histopathological alterations. Serum creatinine slightly increased at 6 hours, indicating that it was less sensitive than Wnt4 expression. These data were further confirmed by clinical study. Both kidney and urinary Wnt4 expression were significantly increased in patients diagnosed with biopsy-proven minimal change disease (MCD) with tubular injury, all of whom nevertheless had normal estimated glomerular filtration rate (eGFR) and serum creatinine. The increased Wnt4 expression also strongly correlated with histopathological alterations in these MCD patients. In conclusion, this is the first demonstration that increases in both kidney and urinary Wnt4 expression can be detected more sensitively and earlier than serum creatinine after kidney injury. In particular, urinary Wnt4 could be a potential noninvasive biomarker for the early detection of tubular injury.
Department of Nephrology, 2nd Affiliated Hospital, Harbin Medical University, Harbin, People's Republic of China.|Department of Nephrology, 1st Affiliated Hospital, Harbin Medical University, Harbin, People's Republic of China.
Shi-Lei
SL
Zhao
Department of Nephrology, 2nd Affiliated Hospital, Harbin Medical University, Harbin, People's Republic of China.
Shi-Yao
SY
Wei
Department of Nephrology, 2nd Affiliated Hospital, Harbin Medical University, Harbin, People's Republic of China.
Yu-Xiao
YX
Wang
Department of Nephrology, 2nd Affiliated Hospital, Harbin Medical University, Harbin, People's Republic of China.
Tian-Tian
TT
Diao
Department of Nephrology, 2nd Affiliated Hospital, Harbin Medical University, Harbin, People's Republic of China.
Jian-Si
JS
Li
Department of Nephrology, 2nd Affiliated Hospital, Harbin Medical University, Harbin, People's Republic of China.
Yi-Xin
YX
He
Department of Nephrology, 2nd Affiliated Hospital, Harbin Medical University, Harbin, People's Republic of China.
Jing
J
Yu
Department of Nephrology, 2nd Affiliated Hospital, Harbin Medical University, Harbin, People's Republic of China.
Xi-Yue
XY
Jiang
Department of Nephrology, 2nd Affiliated Hospital, Harbin Medical University, Harbin, People's Republic of China.
Yang
Y
Cao
Department of Nephrology, 2nd Affiliated Hospital, Harbin Medical University, Harbin, People's Republic of China.
Xin-Yue
XY
Mao
Department of Nephrology, 2nd Affiliated Hospital, Harbin Medical University, Harbin, People's Republic of China.
Qiu-Ju
QJ
Wei
Department of Nephrology, 2nd Affiliated Hospital, Harbin Medical University, Harbin, People's Republic of China.
Yu
Y
Wang
Department of Nephrology, 2nd Affiliated Hospital, Harbin Medical University, Harbin, People's Republic of China.
Bing
B
Li
D058186:Acute Kidney Injury / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D005260:Female; D005455:Fluorescent Antibody Technique; D005919:Glomerular Filtration Rate; D000072596:Hepatitis A Virus Cellular Receptor 1 / Q000378:metabolism; D006801:Humans; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000378:metabolism; D007684:Kidney Tubules / Q000293:injuries* / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D009402:Nephrosis, Lipoid / Q000378:metabolism / Q000473:pathology; D015427:Reperfusion Injury / Q000097:blood / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D015854:Up-Regulation; D060528:Wnt4 Protein / Q000378:metabolism* / Q000652:urine
D015415:Biomarkers; C442240:Havcr1 protein, mouse; D000072596:Hepatitis A Virus Cellular Receptor 1; D019394:Ki-67 Antigen; C555581:WNT4 protein, human; D060528:Wnt4 Protein; C555582:Wnt4 protein, mouse; D003404:Creatinine