Paricalcitol in Fabry Disease

Proteinuria is the predominant risk factor for renal disease progression in Fabry disease (FD). When urine protein excretion is controlled to <0.50 g/24 hr, the rate loss of glomerular filtration rate (GFR) is not significantly different from 0. However, enzyme replacement therapy (ERT) alone does not decrease proteinuria and it has been recommended that patients receiving ERT also receive anti Renin-Angiotensin-System (RAS) therapy. Emerging evidences show that paricalcitol (PCT) reduces proteinuria in presence of intensified inhibition of RAS; however, there is no evidence in FD. The aim of this study is to evaluate the antiproteinuric effect of PCT in FD patients with proteinuria >0.50 g/24 hr persisting despite the ERT and anti-RAS therapy titrated to maximum tolerated dosage.

In patients identified by the inclusion criteria, data will be collected at baseline , during administration of oral Paricalcitol (PCT) (after 1, 3 and 6 months), and three months after PCT withdrawal. PCT will administered at dosage of 1 mcg/day; this dosage was chosen as it is not associated with excessive decline of parathyroid hormone (PTH) levels in most patients

Fourteen Fabry patients will be selected and studied in the first six months of add-on oral PCT (1 mcg/day) and, in order to verify the dependence of proteinuria reduction on PCT, three months after drug withdrawal.

Inclusion Criteria: genetically proven FD stable dose of ERT for at least 12 months stable dose of ACEi or ARB titrated to maximum tolerated dosage for at least 6 months persistent proteinuria >0.50 g/24 h despite the use of ERT and ACEi/ARBs in 2 consecutive samples within 12 weeks Exclusion Criteria: steroid/immunosuppressive treatment or glomerular filtration rate change >30% in the past 3 months PTH levels <20 pg/mL serum phosphorus >5.0 mg/dL serum calcium (adjusted for albumin) >10.0 mg/dL active malignancy.