Relative versus absolute globotriaosylsphingosine changes and kidney outcomes in Fabry disease

Background Plasma globotriaosylsphingosine (lyso-Gb3) concentrations decrease after enzyme replacement therapy (ERT) in patients with Fabry disease (FD). However, it remains unclear whether absolute or relative changes in lyso-Gb3 concentrations better reflect treatment response. We evaluated the clinical relevance of absolute and relative changes in lyso-Gb3 concentrations after ERT. Methods This retrospective observational study included 16 patients with FD (8 males and 8 females) with elevated baseline lyso-Gb3 concentrations and paired measurements at baseline and one year after ERT. Absolute and relative changes in lyso-Gb3 concentrations were assessed, and their relationships with baseline lyso-Gb3 concentrations were examined. Kidney outcomes, including the estimated glomerular filtration rate (eGFR) slope and percent change in urinary albumin-to-creatinine ratio (UACR), were analyzed using linear mixed-effects models. Results ERT significantly reduced plasma lyso-Gb3 concentrations in both sexes. Absolute changes in lyso-Gb3 concentrations were strongly correlated with baseline lyso-Gb3 concentrations, particularly in males, whereas relative changes showed weaker dependence on baseline concentrations. In males, larger relative reductions in lyso-Gb3 concentrations were associated with a slower decline in eGFR. Smaller relative reductions were associated with greater increases in UACR in the overall cohort, but in males this was only a nonsignificant trend. Conclusion Relative changes in lyso-Gb3 concentrations after ERT appeared to be less influenced by baseline lyso-Gb3 concentrations than absolute changes. Associations with kidney outcomes were observed in males but were not demonstrated in females. Relative changes in lyso-Gb3 concentrations may provide additional information for assessing treatment response in FD.