Age-related renal function decline in Fabry disease patients on enzyme replacement therapy: a longitudinal cohort study.

BACKGROUND: Nephropathy is common in Fabry disease (FD). Prior studies of renal function during enzyme replacement therapy (ERT) have primarily used estimated glomerular filtration rate (eGFR). We studied the attrition of renal function in FD by measured GFR (mGFR) and urine protein excretion, and explored the influence of age. METHODS: This was a long-term observational study of a nationwide, family-screened cohort of FD patients. All Danish genetically verified FD patients on ERT, without end-stage renal disease at baseline and with three or more mGFR values were included. RESULTS: In all, 52 patients with consecutive mGFR values (n = 841) over median 7 years (range 1-13) were evaluated. Blood pressure remained normal and urine protein excretion was unchanged. Plasma globotriaosylceramide (Gb-3) levels normalized while plasma lyso-Gb-3 remained abnormal in 34% of patients. Baseline mGFR was 90 ± 3 mL/min/1.73 m2 and rate of renal function loss 0.9 ± 0.2 mL/min/1.73 m2/year. Baseline eGFR was 97 ± 5 mL/min/1.73 m2 and rate of renal function loss 0.8 ± 0.3 mL/min/1.73 m2/year. mGFR was age- adjusted to renal healthy non-FD subjects, giving a standard deviation score of -0.8 ± 0.2 with an annual slope of -0.03 ± 0.01 (P = 0.099), without differences between genders. Age grouping of age-adjusted data showed exaggerated renal function loss with age. Urine albumin-creatinine ratio (UACR) >300 mg/g was associated with faster renal function loss, independent of baseline mGFR, age and gender. CONCLUSIONS: ERT-treated FD patients did not have a faster attrition of renal function than renal healthy non-FD subjects (background population). The rate of renal function loss with age was independent of gender and predicted by high UACR. We suggest cautious interpretation of non-age-adjusted FD renal data.