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.
Highlights
Fabry disease is caused by deficiency of the lysosomal enzyme alpha-galactosidase A, coded by GLA gene on Xq21.3-q22
Since injured podocytes detach into the urine, 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
Summary
Fabry disease is caused by deficiency of the lysosomal enzyme alpha-galactosidase A, coded by GLA gene on Xq21.3-q22. Progressive renal failure is a major complication of Fabry disease. Enzyme replacement therapy (ERT) if initiated late in the course of the disease cannot prevent progressive decrease in the glomerular filtration rate (GFR).[1] Heterogeneity of Fabry disease phenotypes has hampered the establishment of a consensus guideline for when to initiate ERT. While some Fabry patients develop complications in childhood, others may only have minimal symptoms until adulthood. Biomarkers to detect early Fabry nephropathy, when lesions are PLOS ONE | DOI:10.1371/journal.pone.0168346. Biomarkers to detect early Fabry nephropathy, when lesions are PLOS ONE | DOI:10.1371/journal.pone.0168346 December 16, 2016
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
