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

Author(s):Show less -

Kim, Yeawon ^[1] ; Park, Sun-Ji ^[1] ; Manson, Scott R. ^[2] ; Molina, Carlos A. F. ^{[2, 3]} ; Kidd, Kendrah ^[4] ; Thiessen-Philbrook, Heather ^[5] ; Perry, Rebecca J. ^[4] ; Liapis, Helen ^{[6, 7]} ; Kmoch, Stanislav ^{[4, 8]} ; Parikh, Chirag R. ^{[5, 9]} ; Bleyer, Anthony J. ^[4] ; Chen, Ying Maggie ^[1]

Affiliation

^[1] Washington Univ, Sch Med, Dept Internal Med, Div Nephrol, St Louis, MO 63110 - USA

^[2] Washington Univ, Sch Med, Dept Surg, Div Urol, St Louis, MO 63110 - USA

^[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Surg & Anat, Div Urol, Ribeirao Preto - Brazil

^[4] Wake Forest Sch Med, Sect Nephrol, Winston Salem, NC - USA

^[5] Yale Univ, Sch Med, Sect Nephrol, New Haven, CT - USA

^[6] Washington Univ, Sch Med, Pathol & Immunol, St Louis, MO - USA

^[7] Arkana Labs, Little Rock, AR - USA

^[8] Charles Univ Prague, Inst Inherited Metab Disorders, Prague - Czech Republic

^[9] Vet Affairs Med Ctr, Clin Epidemiol Res Ctr, West Haven, CT - USA

• Document type: Journal article
• Source: JCI INSIGHT; v. 2, n. 23 DEC 7 2017.
• Web of Science Citations: 7

Abstract

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. (AU)

• FAPESP's process: 15/17785-6 - Delineating signaling pathways and therapeutic approaches for stimulating kidney repair with obstructive uropathy
• Grantee: Carlos Augusto Fernandes Molina
• Support Opportunities: Scholarships abroad - Research