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P.C.G., R.S.C., and E.M.S. scholarships from Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) (Finance Code 001). P.C.G. also received a sandwich scholarship from CAPES. J.B. received scholarship from Universidade Federal do Parana/Tesouro Nacional. A.O. and M.D.S.N. were funded by Programa Ramon y Cajal, FRIAT, ISCIII RETIC REDINREN RD 016/009 and ISCIII FIS/Fondos FEDER (PI18/01366, PI19/00588, PI19/00815), Sociedad Espanola de Nefrologia.

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Article

Growth differentiation factor-15 (GDF-15) and syndecan-1 are potential biomarkers of cardiac and renal involvement in classical Fabry disease under enzyme replacement therapy

Publicated to:KIDNEY & BLOOD PRESSURE RESEARCH. 47 (4): 229-238 - 2022-04-27 47(4), DOI: 10.1159/000521329

Authors: Gregorio, Paulo C; Biagini, Gilson; da Cunha, Regiane S; Budag, Julia; Maria Martins, Ana; Valino Rivas, Lara; Schiefer, Elberth M; Dolores Sanchez-Nino, Maria; Ortiz, Alberto; Stinghen, Andrea E M; Barreto, Fellype C

Affiliations

Hosp Univ Fdn Jimenez Diaz, Nephrol & Hypertens, Madrid, Spain - Author
IIS Fdn Jimenez Diaz UAM, Madrid, Spain - Author
Univ Autonoma Madrid, Sch Med, Dept Pharmacol, Madrid, Spain - Author
Univ Fed Parana, Basic Pathol Dept, Expt Nephrol Lab, Curitiba, Parana, Brazil - Author
Univ Fed Parana, Dept Internal Med, Postgrad Program Internal Med & Hlth Sci, Curitiba, Parana, Brazil - Author
Univ Fed Parana, Dept Internal Med, Serv Nephrol, Curitiba, Parana, Brazil - Author
Univ Fed Sao Paulo, Unifesp, Peadiatr, Sao Paulo, Brazil - Author
Univ Tecnol Fed Parana, Postgrad Program Elect & Comp Engn, Curitiba, Parana, Brazil - Author
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Abstract

Inflammation and endothelial damage play a pivotal role in Fabry disease (FD) manifestations. In daily clinical practice, FD are mainly monitored by traditional biomarkers of target organ injury, such as serum creatinine and proteinuria, which provide no information about inflammation and endothelial damage.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.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.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.The Author(s). Published by S. Karger AG, Basel.

Keywords

alpha-galactosidaseatherosclerosisbiomarkersdysfunctionendothelial glycocalyxenzyme replacement therapyheart-failureinflammationmanifestationsnephropathyoxidative stressrisktype-1Agalsidase-beta dataAlpha galactosidaseAlpha-galactosidaseBiological markerBiomarkersComplicationEnzyme replacementEnzyme replacement therapyFabry diseaseFemaleGrowth differentiation factor 15HumanHumansInflammationInflammation oxidative stress.Kidney diseaseKidney diseasesOxidative stressProteinuriaSyndecan 1Syndecan-1

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal KIDNEY & BLOOD PRESSURE RESEARCH due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2022, it was in position 40/88, thus managing to position itself as a Q2 (Segundo Cuartil), in the category Urology & Nephrology. Notably, the journal is positioned en el Cuartil Q2 para la agencia Scopus (SJR) en la categoría Cardiology and Cardiovascular Medicine.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 1.3. This indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 14, 2024)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

  • Weighted Average of Normalized Impact by the Scopus agency: 1.16 (source consulted: FECYT Feb 2024)
  • Field Citation Ratio (FCR) from Dimensions: 3.07 (source consulted: Dimensions Jun 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-06-29, the following number of citations:

  • WoS: 5
  • Scopus: 5
  • Europe PMC: 4

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-06-29:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 12.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 12 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 1.5.
  • The number of mentions on the social network X (formerly Twitter): 2 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
  • Assignment of a Handle/URN as an identifier within the deposit in the Institutional Repository: https://repositorio.uam.es/handle/10486/712455

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Brazil.