Fabry disease: Kidney involvement and enzyme replacement therapy

Abstract

when he was 38 years old. At the time of onset of renal insufficiency, proteinuria was approximately 2500 mg/ 24 hours and continued at this level during all the years of follow-up until the patient reached ESRD, when a reduction to 300 mg/24 hours was noted. The patient’s mild to moderate hypertension was well controlled at a level of 130/84 mm Hg with an angiotensin-converting enzyme (ACE) inhibitor until 1 year before the onset of ESRD, when a calcium channel blocker was added. During the 10-year follow-up, the patient’s creatinine clearance (CCr) declined at a rate of 7.9 mL/min/year (Fig. 1). The CAPD program is 4 × 1 L dialysis fluid with 1.5% glucose concentration. The small size of the patient (54 kg body weight and 156 cm height) led to an intolerance of larger intraperitoneal volumes. Before he commenced CAPD, echocardiography revealed a left ventricular mass (LVM) of 430 g and an ejection fraction (EF) of 47%. In view of the renal findings and cardiac dysfunction, enzyme replacement treatment (ERT) with intravenous agalsidase beta (Fabrazyme), 1 mg/kg/body weight initially every other week, was initiated 1 month after he began CAPD. Before the commencement of treatment and after 1.5, 3, 6, 12, and 15 months, weekly residual renal creatinine clearance (wCrCr) and renal Kt/V urea (wKrt/Vurea) were determined according to standard equations. Peritoneal dialysis adequacy was also estimated by weekly peritoneal Kt/V urea (wKpt/Vurea) and creatinine clearance (wCpCr). The latter was adjusted for the patient’s size using a nomogram for body surface area. Table 1 displays routine laboratory investigation before and after ERT. The wCrCr rose after 1.5 months of therapy from 29 to 82 L/week/1.73 m 2 . It remained at approximately 80 L/week/1.73 m 2 after 3 and 6 months of therapy; a decrease to 60 L/week/1.73 m 2 was noticed at month 12 and continued until month 15 of therapy [these values are represented in the figure as Ccr (mL/min)]. Also, the wKrt/Vurea rose strikingly, from 0.8 to 2.3 after 1.5 months, remained around 2.0 after 3 and 6 months, dropped to 1.5 after 12 months, and remained stable after 15 months of treatment. The wCpCr, on the other hand, did not change significantly during the same period. Similarly,