title: Urinary Podocyte Loss Is Increased in Patients with Fabry Disease and Correlates with Clinical Severity of Fabry Nephropathy.
abstract: Chronic kidney disease is a major complication of Fabry disease. Podocytes accumulate globotriaosylceramide inclusions more than other kidney cell types in Fabry patients. Podocyte injury occurs early in age, and is progressive. Since injured podocytes detach into the urine (podocyturia), we hypothesized that podocyturia would increase in Fabry patients and correlate with clinical severity of Fabry nephropathy. Urine specimens from 39 Fabry patients and 24 healthy subjects were evaluated for podocyturia. Most of the Fabry patients and many healthy subjects had podocyturia. The number of podocytes per gram of urine creatinine (UPodo/g Cr) was 3.6 fold greater in Fabry patients (3,741 ± 2796; p = 0.001) than healthy subjects (1,040 ± 972). Fabry patients with normoalbuminuria and normoproteinuria had over 2-fold greater UPodo/g Cr than healthy subjects (p = 0.048). UPodo/gCr was inversely related to eGFR in male patients (r = -0.69, p = 0.003). UPodo/gCr was directly related to urine protein creatinine ratio (r = 0.33; p = 0.04) in all Fabry patients. These studies confirm increased podocyturia in Fabry disease, even when proteinuria and albuminuria are absent. Podocyturia correlates with clinical severity of Fabry nephropathy, and potentially may be of prognostic value.
authors.affiliation: Department of Pathology, University of Washington, Seattle, United States America.
authors.forename: Brent
authors.initials: B
authors.lastname: Fall
authors.affiliation: Department of Pediatrics, University of Washington, Seattle, United States America.
authors.forename: C Ronald
authors.initials: CR
authors.lastname: Scott
authors.affiliation: Departments of Pediatrics, University of Minnesota, Minneapolis, United States America.|Departments of Medicine, University of Minnesota, Minneapolis, United States America.
authors.forename: Michael
authors.initials: M
authors.lastname: Mauer
authors.affiliation: Department of Medicine, University of Washington, Seattle, United States America.
authors.forename: Stuart
authors.initials: S
authors.lastname: Shankland
authors.affiliation: Department of Medicine, University of Washington, Seattle, United States America.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Pippin
authors.affiliation: Department of Medicine, University of Washington, Seattle, United States America.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Jefferson
authors.affiliation: Department of Medicine, University of Alabama, Birmingham, United States America.
authors.forename: Eric
authors.initials: E
authors.lastname: Wallace
authors.affiliation: Department of Medicine, University of Alabama, Birmingham, United States America.
authors.forename: David
authors.initials: D
authors.lastname: Warnock
authors.affiliation: Department of Pathology, University of Washington, Seattle, United States America.
authors.forename: Behzad
authors.initials: B
authors.lastname: Najafian
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D000795:Fabry Disease / Q000150:complications* / Q000175:diagnosis / Q000473:pathology / Q000652:urine*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D050199:Podocytes / Q000473:pathology*; D011379:Prognosis; D011507:Proteinuria / Q000209:etiology / Q000652:urine; D051436:Renal Insufficiency, Chronic / Q000175:diagnosis / Q000209:etiology* / Q000473:pathology / Q000652:urine; D012720:Severity of Illness Index; D014556:Urine / Q000166:cytology*; D055815:Young Adult