Fabry Registry. Nephropathy in males and females with Fabry disease: cross-sectional description of patients before treatment with enzyme replacement therapy.

BACKGROUND: Fabry disease, an X-linked genetic disorder with deficient alpha-galactosidase A activity, is characterized by kidney disease and kidney failure. The spectrum of kidney disease has not been well defined, especially in female patients. METHODS: We did a cross-sectional retrospective analysis of natural history of glomerular filtration rate (estimated- eGFR), albuminuria and proteinuria in 1262 adult patients (585 males, 677 females) from the Fabry Registry. RESULTS: Twenty-eight percent of males (age 20-79 years) and 13% of females (age 20-82 years) had chronic kidney disease (CKD) with eGFR < 60 ml/min/1.73 m(2). Overt proteinuria (>300 mg/24 h) was demonstrated in 43 and 26% of males and females with CKD stage 1, respectively, and the proportions were higher with more severe kidney involvement. However, 11% of males and 28% of females with eGFR < 60 ml/min/1.73 m(2) had proteinuria <300 mg/ 24 h. Of eGFR >/= 60 ml/min/1.73 m(2) patients without overt proteinuria (n = 93), 55% of the males and 35% of the females had albuminuria >30 mg/24 h. Systemic blood pressure was >/=130/80 mmHg in 48% and 67% of patients with eGFR >/= and <60 ml/min/1.73 m(2), respectively, with no significant differences between males and females. Proteinuria values were significantly correlated with systolic blood pressure in both sexes. CONCLUSIONS: Kidney involvement in Fabry disease is more prevalent and heterogeneous than previously reported. Proteinuria is an early complication, but may not be overt in patients with advanced kidney disease. This analysis, which includes more females than males, confirms that a significant proportion of females suffer moderate to severe kidney involvement in Fabry disease.