Expression of uPAR in Urinary Podocytes of Patients with Fabry Disease

Abstract

<i>Background</i>. 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. <i>Methods</i>. This is a cross-sectional study that included controls (<i>n</i> = 20) and Fabry patients (<i>n</i> = 44) either untreated (<i>n</i> = 23) or treated with agalsidase-<i>β</i> (<i>n</i> = 21). <i>Variables</i>. 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. <i>Results</i>. 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 (<i>ρ</i> = 0.5; <i>p</i> = 0.02). Lyso-Gb3 at concentrations found in the circulation of Fabry patients increased uPAR expression in cultured podocytes. <i>Conclusions</i>. 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.