title: Urinary exosomal Wilms' tumor-1 as a potential biomarker for podocyte injury.
abstract: 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.
authors.affiliation: Renal Diagnostics and Therapeutics Unit, NIDDK, National Institutes of Health, 10 Center Dr., Bldg 10, Rm. 3N108, Bethesda, MD 20892-1268. py@nih.gov.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhou
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kajiyama
authors.forename: Takayuki
authors.initials: T
authors.lastname: Tsuji
authors.forename: Xuzhen
authors.initials: X
authors.lastname: Hu
authors.forename: Asada
authors.initials: A
authors.lastname: Leelahavanichkul
authors.forename: Suzanne
authors.initials: S
authors.lastname: Vento
authors.forename: Rachel
authors.initials: R
authors.lastname: Frank
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Kopp
authors.forename: Howard
authors.initials: H
authors.lastname: Trachtman
authors.forename: Robert A
authors.initials: RA
authors.lastname: Star
authors.forename: Peter S T
authors.initials: PS
authors.lastname: Yuen
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism / Q000652:urine; D015153:Blotting, Western; D002460:Cell Line; D004195:Disease Models, Animal; D055354:Exosomes / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D050199:Podocytes / Q000378:metabolism / Q000473:pathology*; D009396:Wilms Tumor / Q000378:metabolism* / Q000652:urine
chemical_list: D015415:Biomarkers
keywords: WT-1; collapsing glomerulopathy; exosomes; focal segmental glomerulosclerosis; podocytopathy