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Growth Differentiation Factor-15 and Syndecan-1 Are Potential Biomarkers of Cardiac and Renal Involvement in
Paulo C Gregório1, Gilson Biagini2, Regiane S da Cunha3
1Basic Pathology Department, Experimental Nephrology Laboratory, Universidade Federal do Paraná, Curitiba, Brazil, paulocezargregorio@gmail.com.
Insights
Growth differentiation factor-15 (GDF-15) and syndecan-1 show promise as biomarkers for cardiac and renal involvement in Fabry disease (FD) patients undergoing enzyme replacement therapy (ERT). Further research is needed to explore their role in disease outcomes.
Area of Science:
- Biochemistry
- Cardiology
- Nephrology
- Genetics
Background:
- Fabry disease (FD) involves inflammation and endothelial damage, impacting cardiac and renal systems.
- Current biomarkers like serum creatinine and proteinuria do not reflect these underlying processes.
- Novel biomarkers are needed to monitor FD progression and treatment efficacy.
Purpose of the Study:
- To investigate serum levels of 3-nitrotyrosine (3-NT), growth differentiation factor-15 (GDF-15), and syndecan-1 in FD patients on enzyme replacement therapy (ERT).
- To assess the relationship between these biomarkers and cardiac and renal manifestations in FD.
- To identify potential markers for disease progression and treatment response.
Main Methods:
- Serum levels of 3-NT, GDF-15, and syndecan-1 were measured in 52 classical FD patients on ERT.
- Patients' cardiac (interventricular septal thickness, cardiomyopathy) and renal (eGFR, proteinuria) parameters were assessed.
- Correlations between biomarkers and clinical manifestations were analyzed using statistical methods, including multivariate analysis.
Main Results:
- Serum GDF-15 correlated with interventricular septal thickness and estimated glomerular filtration rate (eGFR).
- Syndecan-1 correlated with interventricular septal thickness and 24-hour proteinuria.
- GDF-15 levels were higher in patients with cardiomyopathy and in those starting ERT later.
- Multivariate analysis identified syndecan-1, 3-NT, and GDF-15 as differentiators for combined cardiac and renal involvement.
Conclusions:
- GDF-15 and syndecan-1 are associated with cardiac and renal involvement in FD patients on ERT.
- These biomarkers may offer insights into residual risk and disease outcomes.
- Further investigation into their prognostic value is warranted.
Background And Aims:
Inflammation and endothelial damage play a pivotal role in Fabry disease (FD) manifestations. In daily clinical practice, FD is mainly monitored by traditional biomarkers of target organ injury, such as serum creatinine and proteinuria, which provide no information about inflammation and endothelial damage.
Materials And Methods:
We investigated the serum levels of 3-nitrotyrosine (3-NT), an oxidative stress biomarker, and of growth differentiation factor-15 (GDF-15) and syndecan-1 in classical FD patients on enzyme replacement therapy (ERT) for at least 6 months and their relationship with Fabry-related cardiac and renal manifestations.
Results:
Fifty-two classical FD patients (37 females) on ERT for 62.0 ± 27.5 months were included in the study. The main clinical manifestations included nephropathy (67.3%) and cardiomyopathy (21.1%). Serum levels of 3-NT, syndecan-1, and GDF-15 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. There was a direct correlation between interventricular septal thickness and serum GDF-15 (r = 0.59; p < 0.001) and syndecan-1 (r = 0.30, p = 0.04). Among kidney parameters, there was a significant correlation between estimated glomerular filtration rate and GDF-15 (r = -0.61; p < 0.001), as well as between 24 h proteinuria and syndecan-1 (r = 0.28; p = 0.04). Serum GDF-15 levels were significantly higher in patients with cardiomyopathy (p = 0.03) as well in those with both nephropathy and cardiomyopathy (p = 0.02) than in patients without these comorbidities. Serum GDF-15 levels were also significantly higher in patients who started ERT at an older age (≥40 years). In multivariate analysis, syndecan-1, 3-NT, GDF-15, time on ERT, and arterial pressure differentiated Fabry patients with both cardiac and renal involvement from those without these manifestations.
Conclusions:
GDF-15 and syndecan-1 were associated with parameters of cardiac and renal involvement in classic FD patients on ERT. Their potential association with residual risk and disease outcomes should be investigated.
