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Elevated urinary CRELD2 is associated with endoplasmic reticulum stress-mediated kidney disease

Y. Kim, SJ. Park, SR. Manson, CA. Molina, K. Kidd, H. Thiessen-Philbrook, RJ. Perry, H. Liapis, S. Kmoch, CR. Parikh, AJ. Bleyer, YM. Chen,

. 2017 ; 2 (23) : . [pub] 20171207

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc19035496

Grantová podpora
R01 HL085757 NHLBI NIH HHS - United States
UL1 TR001863 NCATS NIH HHS - United States
P30 DK079310 NIDDK NIH HHS - United States
U54 DK083912 NIDDK NIH HHS - United States
R01 DK096177 NIDDK NIH HHS - United States
R21 DK106584 NIDDK NIH HHS - United States
R03 DK106451 NIDDK NIH HHS - United States
UL1 TR000448 NCATS NIH HHS - United States
R01 DK105056 NIDDK NIH HHS - United States
C06 RR015502 NCRR NIH HHS - United States
P30 DK020579 NIDDK NIH HHS - United States
P30 AR057235 NIAMS NIH HHS - United States
K08 DK089015 NIDDK NIH HHS - United States
UL1 TR002345 NCATS NIH HHS - United States
P30 DK079333 NIDDK NIH HHS - United States
NV17-29786A MZ0 CEP - Centrální evidence projektů

ER stress has emerged as a signaling platform underlying the pathogenesis of various kidney diseases. Thus, there is an urgent need to develop ER stress biomarkers in the incipient stages of ER stress-mediated kidney disease, when a kidney biopsy is not yet clinically indicated, for early therapeutic intervention. Cysteine-rich with EGF-like domains 2 (CRELD2) is a newly identified protein that is induced and secreted under ER stress. For the first time to our knowledge, we demonstrate that CRELD2 can serve as a sensitive urinary biomarker for detecting ER stress in podocytes or renal tubular cells in murine models of podocyte ER stress-induced nephrotic syndrome and tunicamycin- or ischemia-reperfusion-induced acute kidney injury (AKI), respectively. Most importantly, urinary CRELD2 elevation occurs in patients with autosomal dominant tubulointerstitial kidney disease caused by UMOD mutations, a prototypical tubular ER stress disease. In addition, in pediatric patients undergoing cardiac surgery, detectable urine levels of CRELD2 within postoperative 6 hours strongly associate with severe AKI after surgery. In conclusion, our study has identified CRELD2 as a potentially novel urinary ER stress biomarker with potential utility in early diagnosis, risk stratification, treatment response monitoring, and directing of ER-targeted therapies in selected patient subgroups in the emerging era of precision nephrology.

Citace poskytuje Crossref.org

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$a ER stress has emerged as a signaling platform underlying the pathogenesis of various kidney diseases. Thus, there is an urgent need to develop ER stress biomarkers in the incipient stages of ER stress-mediated kidney disease, when a kidney biopsy is not yet clinically indicated, for early therapeutic intervention. Cysteine-rich with EGF-like domains 2 (CRELD2) is a newly identified protein that is induced and secreted under ER stress. For the first time to our knowledge, we demonstrate that CRELD2 can serve as a sensitive urinary biomarker for detecting ER stress in podocytes or renal tubular cells in murine models of podocyte ER stress-induced nephrotic syndrome and tunicamycin- or ischemia-reperfusion-induced acute kidney injury (AKI), respectively. Most importantly, urinary CRELD2 elevation occurs in patients with autosomal dominant tubulointerstitial kidney disease caused by UMOD mutations, a prototypical tubular ER stress disease. In addition, in pediatric patients undergoing cardiac surgery, detectable urine levels of CRELD2 within postoperative 6 hours strongly associate with severe AKI after surgery. In conclusion, our study has identified CRELD2 as a potentially novel urinary ER stress biomarker with potential utility in early diagnosis, risk stratification, treatment response monitoring, and directing of ER-targeted therapies in selected patient subgroups in the emerging era of precision nephrology.
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