Antiproteinuric effect of add-on paricalcitol in Fabry disease patients: a prospective observational study.

BACKGROUND

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 h, 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 evidence show that paricalcitol (PCT) reduces proteinuria in the presence of intensified inhibition of RAS; however, there is no evidence in FD. We evaluated the antiproteinuric effect of PCT in FD patients with proteinuria >0.50 g/24 h persisting despite ERT and anti-RAS therapy titrated to maximum tolerated dosage.

METHODS

Fifteen FD patients were selected and studied in the first 6 months of add-on oral PCT (1 µg/day) and, in order to verify the dependence of proteinuria reduction on PCT, 3 months after drug withdrawal.

RESULTS

At baseline, proteinuria was 1.3 ± 0.6 g/24 h. Six months of add-on PCT significantly decreased proteinuria to 0.4 ± 0.3 g/24 h, with levels <0.50 g/24 h achieved in four patients at Month 1, six at Month 3, and in 12 by Month 6, in the absence of changes to BP and GFR. Proteinuria recovered to basal value after drug withdrawal.

CONCLUSIONS

In conclusion, our study is the first evidence that PCT is effective in reducing proteinuria in FD patients in the presence of ERT and anti-RAS therapy.