Fabry disease nephropathy. Compendium of "in vitro" and "in vivo" renal effects of globotriaosylsphingosine

Background: Renal damage in Fabry disease (FD) is a consequence of pathological and progressive glycosphingolipids accumulation, which occurs in different magnitudes among FD phenotypes, but is a constant renal tissue phenomenon in all patients with renal involvement. A significant correlation between plasma Lyso-Gb3 (Gb3 analog) and disease severity, has been described but, there is lack of information from clinical studies regarding the correlation between Lyso-Gb3 and renal events in humans and, the few results have certain discrepancies. In clinical practice it is necessary to have disease-specific biomarkers, non-invasive and useful in diagnosis, prognosis and therapeutic response. Evidence relating to the prognostic value of lyso-GL3 is mixed. Summary: we review the evidence on renal effect of plasma and/or urinary Lyso-Gb3 in FD patients and the usefulness as a biomarker of diagnostic and therapeutic response. Additionally, the in vitro renal effects of Lyso-Gb3 were reviewed. The literature search was conducted in PUBMED, EMBASE, SCOPUS, COCHRANE, and Google academic. Search terms: [Fabry disease+(Lyso-Gb3 or Lyso-GL3)+(“renal” or “kidney”)]. Inclusion criteria: i) "in vitro" studies in which a direct effect of Lyso-Gb3 on kidney tissue has been studied, both in animals and/or humans; ii) Retrospective-or-cross-sectional-or-prospective "in vivo" studies in which a correlation between Lyso-Gb3 and renal clinical events or renal function biomarkers has been studied. Key messages: Ten studies presented evidence of ¨in vitro¨ renal damage due to Lyso-Gb3; 4 studies presented correlation between plasma Lyso-Gb3 and renal events in FD patients; 3 studies reported correlation between urinary Lyso-Gb3 and renal events in FD patients.Conclusion: The small number of publications and the methodological heterogeneity do not allow a statistical analysis of them. Regarding the ¨in vivo¨ and ¨in vitro¨ renal effects of Lyso-Gb3 in FD: There is evidence of harmful effects on renal cells in vitro due to Lyso-Gb3 but this evidence is not sufficient to use Lyso-Gb3 (neither plasma nor urinary) as a biomarker for monitoring renal damage in FD patients. Plasma Lyso-Gb3 is a useful biomarker in i) FD diagnosis and, ii) stratification of phenotype and severity of FD. In FD ¨classic¨ patients receiving ERT, it is useful to determine plasma Lyso-Gb3 periodically, because an inconsistent reduction during ERT may indicate the formation of neutralizing anti-agalsidase antibodies.