Urinary exosomal Wilms' tumor-1 as a potential biomarker for podocyte injury

• Published in: American journal of physiology. Renal physiology 2013-08, Vol.305 (4), p.F553-F559
• Main Authors: Zhou, Hua, Kajiyama, Hiroshi, Tsuji, Takayuki, Hu, Xuzhen, Leelahavanichkul, Asada, Vento, Suzanne, Frank, Rachel, Kopp, Jeffrey B, Trachtman, Howard, Star, Robert A, Yuen, Peter S T
• Format: Article
• Language: English
• Subjects: Animals; Biomarkers; Biomarkers - metabolism; Biomarkers - urine; Biopsy; Blotting, Western; Cell Line; Cells; Disease Models, Animal; Exosomes - metabolism; Humans; Immunoblotting; Kidney - metabolism; Kidney - pathology; Kidney diseases; Mice; Podocytes - metabolism; Podocytes - pathology; Rodents; T cell receptors; Tumors; Wilms Tumor - metabolism; Wilms Tumor - urine
• ISSN: 1931-857X; 1522-1466
• DOI: 10.1152/ajprenal.00056.2013

Renal Wilms' tumor-1 (WT-1) staining is used to detect podocyte loss in kidney biopsies. We aimed to determine if urinary exosomal WT-1 could serve as a noninvasive biomarker of podocyte injury. We examined WT-1 by Western blot in a human podocyte-like cell line, a mouse model of podocyte injury, and human subjects with podocyte disorders. WT-1 was detected in exosomal fraction of the conditioned media from podocytes and increased 48 h after hTGF-β1 stimulation. Cellular WT-1 decreased in podocytes following hTGF-β1 incubation. In mice with induced podocyte injury, urinary exosomal WT-1 was detected 1 wk earlier than albuminuria and also tracked the effects of angiotensin receptor blocker (ARB) treatment. In addition, urinary exosomal WT-1 levels at 1 wk post-injury correlated with the severity of glomerular injury at 3 wk later. In human subjects, urinary exosomal WT-1 was significantly increased in focal segmental glomerulosclerosis (FSGS) patients compared with healthy volunteers or steroid-sensitive nephrotic syndrome (SSNS) patients. Urinary exosomal WT-1 was also significantly decreased in patients in remission for either FSGS or SSNS or following steroid treatment in six SSNS subjects. We conclude that urinary exosomal WT-1 is a promising noninvasive biomarker with apparent podocyte specificity that can detect early progression and treatment-induced regression of podocyte injury in FSGS or SSNS. These results warrant longitudinal, prospective studies in a large cohort with a range of podocyte diseases.