期刊
JCI INSIGHT
卷 2, 期 23, 页码 -出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/jci.insight.92896
关键词
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资金
- NIH [P30AR057235, C06RR015502, RO1 HL085757, R21DK106584, R01 DK105056A1, R03DK106451, K08DK089015]
- New Investigator Award from National Kidney Foundation
- Midwest Stone Institute grant
- NIH/NIDDK [R01DK096177]
- Brazilian grant from Sao Paaulo Research Foundation - FAPESP [2015/17785-6]
- Ministry of Education, Youth and Sports of the Czech Republic [LQ1604 NPU II]
- Ministry of Health of the Czech Republic [NV17-29786A]
- O'Brien Kidney Center grant [P30DK079310]
- Halpin Foundation-American Society of Nephrology Research grant
- Children's Discovery Institute of Washington University [MD-FR-2013-336]
- Clinical Scientist Development Award from the Doris Duke Charitable Foundation [2015100]
- Career Development Award from the Nephrotic Syndrome Study Network (NEPTUNE)
- Early Career Development Award from the Central Society for Clinical and Translational Research (CSCTR)
- Renal Translational Innovation grant from Washington University Division of Nephrology
- St. Louis Children's Hospital [MD-FR-2013-336]
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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