Paradoxical Dapagliflozin Effect on Proteinuria in a Female Patient with Classic Fabry Disease First Literatura Report

Abstract

A 75-year-old female patient, with “classic” Fabry disease (DEL 3&4 EXON, GLA gene) and severe multi-organic compromise (cardiac, brain, renal and peripheral nervous system) is presented. Patient presented treatment initiation criteria, and was a “classic” Fabry phenotype, for this reason, agalsidase-β was indicated. In addition, enalapril, were indicated. After the treatment start and to date, the patient presented: i) LVH stabilization; ii) brain damage stabilization; iii) stable eGFR and sustained improvement in proteinuria and; iv) pain improvement. In September 2022, due to the results of DAPA-CKD study, it was decided to start treatment with dapagliflozin to extend the renal protective effect; patient presented good tolerance to drug and no adverse effects were recorded. A slight decrease in eGFR was observed, but suspension was decided after 8 weeks due to increased proteinuria. Kidney disease is a major Fabry disease complication; it is more severe in the “classic” phenotype and males, although the “non-classic” Fabry phenotype and affected females may also present severe renal disease. Patients with Fabry disease and chronic kidney disease have a high risk of cardiovascular events, SGLT-2 inhibitor drugs have shown favorable effects on cardiovascular events in chronic kidney disease patients, both DBT and non-DBT. Multiple pathophysiological mechanisms have been described in Fabry nephropathy, none of them could explain, the reason why SGLT-2 blockade produced an increase in proteinuria in presented case.