Growth Differentiation Factor-15 and Syndecan-1 Are Potential Biomarkers of Cardiac and Renal Involvement in Classical Fabry Disease under Enzyme Replacement Therapy

Kidney Blood Press Res. 2022;47(4):229-238. doi: 10.1159/000521329.

PMID: 35086103

Paulo C Gregório, Gilson Biagini, Regiane S da Cunha

Highlights: Growth Differentiation Factor-15 (GDF-15) and Syndecan-1 were associated with parameters of cardiac and renal involvement in classic Fabry disease patients on enzyme replacement therapy (ERT). Their potential association with residual risk and disease outcomes should be investigated.

Abstract

Background and aims: Inflammation and endothelial damage play a key part in the symptoms of Fabry disease (FD). Traditional indicators of target organ damage, such as serum creatinine and proteinuria, are used to monitor FD in everyday clinical practice, but they provide little information on inflammation or endothelial damage.

Materials and methods: In classical FD patients on enzyme replacement therapy (ERT) for at least 6 months, we looked at serum levels of 3-nitrotyrosine (3-NT), an oxidative stress biomarker, as well as growth differentiation factor-15 (GDF-15) and syndecan-1, and their relationship with Fabry-related cardiac and renal manifestations.

Results: The study included 52 classical FD patients (37 females) who had been on ERT for 62.0 ± 27.5 months. Nephropathy (67.3%) and cardiomyopathy (21.1%) were the most common clinical symptoms. 3- NT, syndecan-1, and GDF-15 serum concentrations were 33.3 (4.8-111.1) nmol/mL, 55.7 (38.8-74.9) ng/mL, and 541.8 (392.2-784.4) pg/mL, respectively. Interventricular septal thickness was found to have a direct relationship with serum GDF-15 (r = 0.59; p < 0.001) and syndecan-1 (r = 0.30, p = 0.04). There was a significant relationship between estimated glomerular filtration rate and GDF-15 (r = -0.61; p < 0.001), as well as 24 h proteinuria and syndecan-1 (r = 0.28; p = 0.04), among renal parameters. Patients with cardiomyopathy (p = 0.03) and those with both nephropathy and cardiomyopathy (p = 0.02) had significantly greater serum GDF-15 levels than those without these comorbidities. Patients who began ERT at an older age (≥40 years) had significantly greater serum GDF-15 levels. Syndecan-1, 3-NT, GDF-15, time on ERT, and arterial pressure were used in multivariate analysis to distinguish Fabry individuals with cardiac and renal dysfunction from those who did not have these symptoms.

Conclusions: In classic FD patients on ERT, GDF-15 and syndecan-1 were linked to cardiac and renal involvement parameters. It's important to look into their possible link to residual risk and disease outcomes.

Keywords: Biomarkers, Enzyme replacement therapy, Fabry disease, Inflammation, Oxidative stress