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Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Int+J+Nephrol 2017 ; 2017 (ä): ä Nephropedia Template TP
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Expression of uPAR in Urinary Podocytes of Patients with Fabry Disease #MMPMID28523190
Int J Nephrol 2017[]; 2017 (ä): ä PMID28523190show ga
Background. Despite enzyme replacement therapy, Fabry nephropathy still progresses. Podocyturia is an irreversible event that antedates proteinuria and leads to chronic renal failure. We evaluated a potential mechanism of podocyte detachment via the expression of the urokinase-type Plasminogen Activator Receptor (uPAR) in urinary podocytes of Fabry patients. Methods. This is a cross-sectional study that included controls (n = 20) and Fabry patients (n = 44) either untreated (n = 23) or treated with agalsidase-? (n = 21). Variables. Variables are estimated glomerular filtration rate (eGFR), urinary protein?:?creatinine ratio, and urinary uPAR+ podocyte?:?creatinine ratio. uPAR mRNA expression in response to lyso-Gb3, a bioactive glycolipid accumulated in Fabry disease, was studied in cultured human podocytes. Results. Controls and Fabry patients had similar age, gender, and renal function. Urinary uPAR+ podocytes were higher in patients than in controls. Untreated patients were significantly younger; had more females, and presented lower urinary protein?:?creatinine ratios and significantly higher urinary uPAR+ podocytes than treated subjects. In treated patients, urinary uPAR+ podocytes correlated with urinary protein?:?creatinine ratio (? = 0.5; p = 0.02). Lyso-Gb3 at concentrations found in the circulation of Fabry patients increased uPAR expression in cultured podocytes. Conclusions. Urinary podocytes expressing uPAR are increased in Fabry patients, especially in untreated patients. The potential contribution of uPAR expression to podocyte detachment merits further studies.