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.

• MeSH
• akutní poškození ledvin diagnóza   etiologie   patofyziologie   moč   MeSH
• biologické markery moč   MeSH
• dítě MeSH
• extracelulární matrix - proteiny fyziologie   moč   MeSH
• intersticiální nefritida genetika   patofyziologie   moč   MeSH
• kardiochirurgické výkony MeSH
• lidé MeSH
• molekuly buněčné adheze fyziologie   moč   MeSH
• mutace MeSH
• myši inbrední C57BL MeSH
• nefrotický syndrom diagnóza   patofyziologie   moč   MeSH
• podocyty metabolismus   MeSH
• pooperační komplikace moč   MeSH
• stres endoplazmatického retikula fyziologie   MeSH
• uromodulin genetika   MeSH
• zvířata MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH