Early Risk Stratification for Natural Disease Course in Fabry Patients Using Plasma Globotriaosylsphingosine Levels.
Clin J Am Soc Nephrol
; 18(10): 1272-1282, 2023 10 01.
Article
en En
| MEDLINE
| ID: mdl-37499686
ABSTRACT
BACKGROUND:
Fabry disease is a very heterogeneous X-linked lysosomal storage disease. Disease manifestations in the kidneys, heart, and brain vary greatly, even between patients of the same sex and with the same disease classification (classical or nonclassical). A biomarker with a strong association with the development of disease manifestations is needed to determine the need for Fabry-specific treatment and appropriate frequency of follow-up because clinical manifestations of the disorder may take decennia to develop.METHODS:
We investigated the levels of plasma lysoGb3 levels over time and its association with disease manifestations and disease course in 237 untreated patients with Fabry disease (median age 42 years, 38% male) using linear mixed-effect models.RESULTS:
LysoGb3 levels are stable over time in plasma of untreated patients with Fabry disease. Higher levels of lysoGb3 were associated with steeper decline in eGFR ( P = 0.05) and a faster increase in albuminuria (measured as the urinary albumin-to-creatinine ratio, P < 0.001), left ventricular mass (measured on echocardiography, P < 0.001), left atrial volume index ( P = 0.003), and Fazekas score ( P = 0.003). In addition, regardless of age, higher lysoGb3 levels were associated with higher relative wall thickness ( P < 0.001) and unfavorable functional markers on echocardiography, including septal mitral annular early diastolic velocity (e', P < 0.001) and the ratio of early transmitral velocity (E) to e' (E/e', P = 0.001).CONCLUSIONS:
In an individual patient with Fabry disease, the plasma lysoGb3 level reached a specific level in early childhood which, in the absence of Fabry-specific treatment, remained stable throughout life. The level of lysoGb3 in untreated patients was associated with nearly all Fabry-specific disease manifestations, regardless of the sex of the patient.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Enfermedad de Fabry
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Adult
/
Child, preschool
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Clin J Am Soc Nephrol
Asunto de la revista:
NEFROLOGIA
Año:
2023
Tipo del documento:
Article
País de afiliación:
Países Bajos