Background: Vascular endothelial growth factor (VEGF) is associated with renal pathogenesis of Fabry disease (FD). Proteomic studies have demonstrated that circulating levels of VEGF are higher in young FD patients compared with controls and an overexpression of tissue VEGF in animal models of Fabry nephropathy has been reported. In kidneys, VEGF-A is predominantly produced by podocytes, and its action on endothelial dysfunction is known. An alternative VEGF-A isoform, VEGF-A165b, confers benefit in microvascular disease states, and it was studied in diabetic nephropathy having demonstrated a protective function, acting on the restoration of the podocyte glycol-calyx.

Methods: cross-sectional design. Urinary mRNA was obtained by RT-qPCR

Results: 48 subjects were included; 24 FD patients (17F/7M - 23.7±17.5 ys) and 24 healthy volunteers (17F/7M - 23.0±17.0 ys). 12 adults and 12 pediatrics in both populations Median uACR (p=0. 999) and eGFR (p=0. 999) were similar between both groups. FD genotypes included were R301Q, R363H, R227Q, del3&4exon, L106R, E398X, L415P and C238Y; 15 FD patients were treatment naïve and 9 receiving ERT (agalsidase-β); median time of ERT was 15.6±28.3 months. Comparative expression of urinary VEGF-165b-mRNA was higher among FD patients versus controls although without statistical significance (p=0.369). No significant correlations were found between urinary VEGF-165b-mRNA and variables “Age” (p=0.845), “Gender” (p=0.369), “αGal-A” (p=0.631), “Genotype” (p=0.142), “Phenotype” (p=0.898), “uACR” (p=0.744), “eGFR” (p=0.059) and “ERT or Naïve” (p=0.507). A significant correlation between urinary VEGF-165b-mRNA and “time of ERT treatment” was found (p=0.05).

Conclusion: overexpression of urinary VEGF-165b-mRNA (with known renal cyto-protective effects) is a probable response to injury in FD nephropathy. The only variable correlated with the highest urinary expression of VEGF-165b-mRNA was the time of ERT treatment. Probably in patients with longer treatment time there is a decrease in FD damage. A limitation of the present work is the low sample size and cross-sectional design.