Interpretation of GFR slope in untreated and treated adult fabry patients.

Nephropathy is one of the main features of Fabry disease (FD) that leads, in untreated patients with classical mutations, to end-stage renal disease (ESRD) from the third to the fifth decade of life. The availability of a specific treatment modified the natural history of FD; in particular, it was widely reported that Enzyme Replacement Therapy (ERT) is able to slow the progression of the disease. Regarding Fabry Nephropathy, several reports have documented an elevated estimated glomerular filtration rate (eGFR) slope in untreated patients as expression of a rapid disease progression towards ESRD. Otherwise, the prompt start of treatment may be beneficial in stabilizing renal function or slowing its decline. Therefore, based on data of the literature about the effects of ERT on eGFR decline, and on the evidence supporting the role of eGFR slope as a surrogate end point for chronic kidney disease (CKD) progression, we could suggest, in this 'Expert Opinion', that a treatment should be defined effective when eGFR decline is < 1 ml/min/1,73 m2 per year, and not effective when the eGFR loss remains ≥ 3 mL/min/1,73 m2 per year (≥ 2.5 mL/min/1,73 m2 per year in females). Moreover, practical clinical recommendations and guidance for Fabry patients suggested that treatment switch may be appropriate if individualized therapeutic goals are not achieved. Since a dose dependent efficacy has been demonstrated for ERT, we suggest to consider a switch to higher doses of ERT in symptomatic adult Fabry patients (aged 18-60 years) with eGFR 45 to 90 mL/min/1,73 m2 and treated with a stable dose of ERT for at least one year, in which a linear negative slope of eGFR of 3 mL/min/1,73 m2/year for males (2.5 mL/min/1,73 m2 /year for females) was observed.