Autori: Angela Maria Pellegrino, Luigi Annicchiarico Petruzzelli, Fortunato Petrillo, Enrica Emanuela Cascone, Maria Amicone, Cristina Marchetiello, Eleonora Riccio, Antonio Pisani
Affiliazioni: Chair of Nephrology, Department of Nephrology, Federico II University of Naples
Background and objectives: Fabry disease (FD) is an X-linked disorder caused by lysosomal α-galactosidase A deficiency, with subsequent deposition of undegraded glycosphingolipid products, mainly globiotriaosylceramide (Gb3), in multiple organs (REF).Progressive nephropathy is one of the main features of Fabry disease (FD). The high prevalence of proteinuria in patients with FD and the suggested sequence of events leading from microalbuminuria to proteinuria, and ultimately to chronic kidney disease (CKD), are very similar to diabetic nephropathy history, where a glomerular hyperfiltration is the firts step. Surprisingly, although hyperfiltration in FD has been reported in several studies, its prevalence is at present unknown. The focus of our study was to determine the prevalence of glomerular hyperfiltration in a cohort of patients with FD and to identify the factors associated with a high risk of hyperfiltration.
Methods: To address this issue, as well as the clinical and biologic correlates of hyperfiltration, a multi-center study of 87 patients with genetically confirmed FD was performed. Only patients with normal renal function at time of enrollment were recruited in the study. Renal function was estimated using CKD-EPI equation, which has recently been shown to be more accurate in patients with higher eGFR values than MDRD equation in diabetic patients. We defined normal renal function as an eGFR ≥ 90 mL/min per 1.73 m2; glomerular hyperfiltration was defined above a threshold value of eGFR of 125 mL/min per 1.73 m2.
Results: A total of 87 patients with available data on eGFR were studied. Clinical and biologic parameters of the overall population (all patients with FD) are shown in Table 1.
After excluding patients with hypofiltration (n = 10), 77 patients had normal renal function: these patients were further divided in 30 patients with hyperfiltration and 47 patients without hyperfiltration. The prevalence of hyperfiltration assessed by CKD-EPI estimated GFR was 39% of patients with normal renal function. Among patients with hyperfiltration, 70% had hyperfiltration alone, whereas 26.7% and 3.3% had an associated microalbuminuria or macroalbuminuria, respectively (Table 2). In patients with no albuminuria, hyperfiltration status was significantly associated with a young age, the absence of cardiac involvement and the absence of Fabry-related symptoms. No association was found with the genetic mutation, the enzymatic activity, and the ultrasound kidney size.
Conclusions: Hyperfiltration is a very common feature in the first phase of Fabry disease, and its prevalence is greater in younger patients without other signs or symptoms.
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