SP017MALE FABRY PATIENTS TREATED WITH ENZYME REPLACEMENT THERAPY: RENAL PROGRESSION RATES REFLECT AVERAGED URINE PROTEIN TO CREATININE RATIOS

Abstract

Introduction and Aims: Male patients with the classic Fabry disease phenotype progress to end-stage renal disease by their 5th decade of life. Enzyme replacement therapy (ERT) has changed the course of Fabry nephropathy, but the importance of proteinuria on the rate of progression has not been adequately emphasized. We analyzed the rate of loss of estimated glomerular filtration rate (eGFR), in the 3 largest prospective studies of ERT with Agalsidase-Beta (Fabrazyme) @ 1 mg/kg body weight (BW) every other week (qow), and stratified by the averaged urinary protein-to-creatinine ratio (UPCR) at ≤ or >0.5 g/g, determined for each participant with follow-up between 1.5 and 10 years. Methods: We analyzed 179 ERT-treated males: 50 from the phase 3-extension study (P3x; JASN 18:1547;2007(NTC00074971)); 45 from the phase 4 study (P4; Ann Intern Med 146:77; 2007 (NTC00074984)) and 84 males from the Fabry Registry (NDT 27:1042; 2012 (NTC00196742)). Also analyzed were 27 males who received placebo infusions during the phase 4 study. The eGFR was calculated from serum creatinine and demographics (CKD-EPI eGFR) and the slope change in eGFR (ml/min/1.73 m2/year) calculated from at least three serum creatinine measurements, using a mixed effect regression model. The median age for each patient was derived from the time of the first serum creatinine measurement for eGFR. The combined values represent weighted averages of the unique groups. Results: The weighted median age of these 206 male Fabry patients was 36.6 years. The eGFR slopes ml/min/1.73 m2/year), stratified by UPCR ≤ or >0.5 g/g are shown in the table. Conclusions: ERT given at 1 mg/kg BW qow was associated with a clinically significant (66%) reduction in the eGFR slope (-1.54 versus placebo-control -4.49 ml/min/1.73 m2/year) among male Fabry patients with UPCR maintained ≤ 0.5 g/g. For male patients with averaged UPCR above 0.5 g/g, the eGFR slope was similar to placebo-control patients. The median age was greater for those with UPCR >0.5 g/g than ≤0.5 g/g. There was a clinically significant reduction in the eGFR slope (53%) between ERT-treated patients with averaged UPCR ≤0.5 g/g (-1.54 ml/min/1.73 m2/ year) and relevant placebo-controls (-3.24 ml/min/1.73 m2/year). These combined results support the importance of control of UPCR for slowing the rate of loss of eGFR in male Fabry patients receiving ERT at 1 mg/kg BW qow. (Table Presented).