Progressive renal failure is a major complication of Fabry disease (FD). Heterogeneity of FD phenotype has hampered establishment of a consensus guideline for the need and dose adjustment for enzyme replacement therapy (ERT). This is while both age of ERT initiation and ERT dosage can affect its efficacy [1, 2]. Thus, late ERT initiation when patients have >1 g/d proteinuria cannot prevent progressive glomerular filtration rate (GFR) decline and lower ERT doses are less efficacious in clearing podocytes (PC), an essential cell in FN progression, from globotriaocylceramide (GL3) [2]. Therefore, there is a strong need for a biomarker to detect early FD nephropathy (FN) and stratify patient based on FN risk to guide treatment initiation and dose adjustment. Currently, proteinuria and microalbuminuria are used for this purpose [3, 4], but, these are not sensitive to detect early FN lesions [3, 5, 6] and are much less precise renal disease predictors in females with FD [7]. Biopsy studies suggest PC injury occurs early and is progressive with increasing age in young FD patients [5]. Thus, markers of PC injury are promising candidates to detect early FN. PC have limited capacity to regenerate [8]. PC injury and loss leads to segmental and global glomerulosclerosis [9, 10], common and irreversible lesions in late stages of FN. Injured PC fall into the urine. Quantification of urine PC (podocyturia [PCU]) is robust evidence of PC injury with diagnostic and prognostic values in other kidney diseases [11-13]. It is likely that PCU in FD precedes and leads to proteinuria, glomerulosclerosis and reduced GFR. If true, PCU may be useful to predict FN risk and guide FD treatment. Preliminary data show that urine apoptotic PC per creatinine (hereafter used interchangeably with PCU for simplicity) correlates with age, urinary albumin (UACR) and protein creatinine ratios (UPCR) in adult FD patients. However, we have no information about PCU in young FD patients, where a non-invasive and sensitive biomarker of FN is most needed to guide treatments.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
2U54NS065768-06
Application #
8907070
Study Section
Special Emphasis Panel (ZTR1-CI-8 (01))
Program Officer
Morris, Jill A
Project Start
Project End
Budget Start
2014-09-30
Budget End
2015-07-31
Support Year
6
Fiscal Year
2014
Total Cost
$59,350
Indirect Cost
$13,000
Name
University of Minnesota Twin Cities
Department
Type
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
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