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.
| Original language | English (US) |
|---|---|
| Article number | e0168346 |
| Journal | PloS one |
| Volume | 11 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 2016 |
Bibliographical note
Funding Information:This study was supported by an investigator-initiated research grant to BN from Genzyme (a Sanofi company). BN is a recipient of investigator initiated Genzyme research grants, a consultant to Genzyme and has received speaker's honoraria and travel support from Genzyme. He is also a member of the Medical Advisory Board of Amicus and performs kidney biopsy studies for Amicus. MM is a member of the Genzyme sponsored North American Fabry Registry Advisory Board, a recipient of investigator initiated Genzyme research grants, a consultant to Genzyme for clinical trial design, and a speaker at Genzyme educational meetings. He is also a consultant to and performs kidney biopsy studies for Amicus and a grant reviewer for Shire. DW is consultant to Genzyme, Protalix, Actelion, and Amicus. ELW has received honoraria for lectures and participates in the National Fabry Registry Advisory Board sponsored by Genzyme. RS is on the Genzyme board of advisors for Fabry disease. BF, SS, JP, JJ, and PH did not have any relevant financial disclosure. These interests have been reviewed and managed according to the conflict of interest policies of authors' affiliated institutions.
Publisher Copyright:
© 2016 Fall et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
