A U.S. patent was issued on 12/18/2018 to Division of Nephrology faculty member Ying (Maggie) Chen, MD, PhD, and co-inventor Yeawon Kim for their discovery of noninvasive biomarkers that have the potential to help diagnose certain human kidney diseases in their earliest stages of development.
The patent is based on their research published in JCI Insight where they were the first to report that a newly identified protein called cysteine-rich with EGF-like domains 2 (CRELD2) is induced and secreted under endoplasmic reticulum (ER) stress. ER stress contributes to the pathogenesis of various human kidney diseases such as congenital nephrotic syndrome, familial focal segmental glomerulosclerosis, Alport syndrome and ischemic acute kidney injury (AKI).
CRELD2 proved to be a sensitive urinary biomarker for ER stress in certain murine models of ER stress–induced nephrotic syndrome and AKI, and was detectable in urine before clinical or histologic manifestation of kidney disease. More importantly, Chen and Kim demonstrated that the CRELD2 biomarker had potential use in human disease. An increase in urinary CRELD2 was found in patients with autosomal dominant tubulointerstitial kidney disease caused by mutations in the UMOD gene that encodes uromodulin, which is a prototypical tubular ER-stress disease. In addition, in pediatric patients undergoing cardiac surgery, urine levels of CRELD2 were detectable within 6 hours after surgery and were strongly associated with the development of post-surgery AKI.
Using CRELD2 to detect the beginning stages of ER stress-mediated kidney disease, even before a kidney biopsy is clinically indicated, will allow for early management of a select subgroup of patients in the emerging era of precision nephrology. There is a huge potential for applying CRELD2 and other ER stress biomarkers in clinical practice.
Read more about the CRELD2 study here. The issuance of the patent entitled “Methods of detecting biomarkers of endoplasmic reticulum (ER) stress–associated kidney diseases” is also posted by the Washington University Office of Technology Management.