Urinary excretion profile of microRNAs related to renal fibrosis in Fabry disease patients. A pilot study

Abstract

Irreversible renal histological lesions, including glomerulosclerosis and tubulo-interstitial fibrosis, have been described in asymptomatic Fabry disease (FD) patients with normal estimated glomerular filtration rate (eGFR) and mild or absent proteinuria. However, it is currently recommended to start FD treatment in presence of clinical manifestations. During renal fibrosis miR-21, miR-192, and miR-433 that promote fibrosis are activated by TGF-β, and miR-29 and miR-200 that suppress fibrosis, are inhibited by TGF-β. The aim of this work is to compare the urinary excretion of microRNAs related to renal fibrosis in FD patients with healthy subjects. In addition, the microRNAs urinary excretion was related to study population clinical variables. Results: 24 FD patients and 10 healthy subjects of similar characteristics were compared. Asymptomatic FD women with normal α-galactosidase-A (α-gal-A) enzyme activity and symptomatic FD women with normal α-gal-A enzyme activity, who were receiving enzyme replacement therapy (ERT) presented a microRNAs urinary profile excretion similar to controls. Asymptomatic FD men or women patients with decreased α-gal-A enzyme activity presented significant differences in miR-29 (p = 0.0478) and miR-200 (p = 0.0426) compared with controls. Symptomatic FD men with decreased α-gal-A enzymatic activity, who were receiving ERT presented significant differences in miR-200 (p = 0.0238) compared with controls. Conclusion: In asymptomatic FD patients with decreased α-gal-A enzymatic activity a microRNA profile indicative of renal fibrosis was found. These patients, at present, are not treated because they do not present clinical criteria to start ERT. In this population, the microRNAs urinary profile excretion could be useful to detect renal fibrosis in early stages.