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Analysis of institutional authors

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September 19, 2022
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Article

Sodium-glucose co-transporter-2 inhibitors increase Klotho in patients with diabetic kidney disease: A clinical and experimental study

Publicated to:BIOMEDICINE & PHARMACOTHERAPY. 154 113677- - 2022-10-01 154(), DOI: 10.1016/j.biopha.2022.113677

Authors: Mora-Fernandez, Carmen; Sanchez-Nino, Maria Dolores; Donate-Correa, Javier; Martin-Nunez, Ernesto; Perez-Delgado, Nayra; Valino-Rivas, Lara; Fernandez-Fernandez, Beatriz; Ortiz, Alberto; Navarro-Gonzalez, Juan F

Affiliations

GEENDIAB Grp Espanol Estudio Nefropatia Diab, Sociedad Espanola Nefrol, Santander, Spain - Author
Hosp Univ Nuestra Senora Candelaria HUNSC, Unidad Invest, Santa Cruz De Tenerife, Spain - Author
Hospital Universitario Fundación Jiménez Díaz , Instituto de Salud Carlos III - Author
Hospital Universitario Fundación Jiménez Díaz , Instituto de Salud Carlos III , Sociedad Española de Nefrología - Author
Hospital Universitario Nuestra Senora de Candelaria , Instituto de Salud Carlos III - Author
Hospital Universitario Nuestra Senora de Candelaria , Instituto de Salud Carlos III , Sociedad Española de Nefrología - Author
Hospital Universitario Nuestra Senora de Candelaria , Universidad de la Laguna , Instituto de Salud Carlos III , Servicio de Nefrología , Sociedad Española de Nefrología - Author
HUNSC, Serv Anal Clin, Santa Cruz De Tenerife, Spain - Author
HUNSC, Serv Nefrol, Santa Cruz De Tenerife, Spain - Author
Inst Salud Carlos III, RICORS2040 Kidney Dis, Madrid, Spain - Author
Servicio de Análisis Clínicos - Author
Univ Autonoma Madrid, Dept Farmacol, Madrid, Spain - Author
Univ Autonoma Madrid, Fdn Jimenez Diaz, Inst Invest Sanit, Madrid, Spain - Author
Univ Laguna, Inst Tecnol Biomed, Tenerife, Spain - Author
Universidad Autónoma de Madrid , Hospital Universitario Fundación Jiménez Díaz , Instituto de Salud Carlos III - Author
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Abstract

Sodium-glucose co-transporter-2 inhibitors (SGLT2i) provide cardiorenal protection. However, the molecular mechanisms remain poorly understood. We explored the impact of SGLT2i on Klotho, a kidney-derived protein with antiaging, renal-protective and heart-protective properties. A real world prospective observational study addressed the impact of initiating SGLT2i (canagliflozin, dapagliflozin, empagliflozin) or dipeptidyl peptidase-4 inhibitors (DPP4i) in patients with early diabetic kidney disease (DKD). Serum and urinary soluble Klotho, albuminuria and serum and urinary tumor necrosis factor-alpha (TNFa) were measured. The effect of SGLT2i on Klotho mRNA and protein was explored in vitro in kidney proximal tubular cells stressed with high glucose concentrations to simulate the diabetic milieu, albumin to simulate albuminuria, and the inflammatory cytokine TWEAK to simulate the inflammatory environment in DKD. Baseline urinary Klotho was negatively associated with albuminuria (r − 0.45, P < 0.001) and urinary TNFa (r − 0.40, P < 0.01). Both DPP4i and SGLT2i reduced HbA1c similarly, but only SGLT2i decreased eGFR, albuminuria and urinary TNFa and increased (P < 0.001) serum (5.2 %) and urinary Klotho (38.9 %). Changes in urinary TNFa (β − 0.53, P = 0.001) and albuminuria (β − 0.31, P < 0.05) were independently associated with changes in urinary Klotho (adjusted R2 = 0.54, P < 0.001). Studies in renal tubular cells demonstrated that high glucose, albumin and TWEAK decreased Klotho mRNA expression and protein levels, an effect similarly prevented by SGLT2i. SGLT2i increase Klotho availability in type 2 diabetic patients with poorly controlled diabetes and early DKD, as well as in stressed tubular cells. This effect on Klotho may contribute to the kidney and heart protection afforded by SGLT2i.

Keywords

albuminuriadiabetes mellitusdiabetic kidney diseaseempagliflozinexpressioninflammationklothomechanismmicenephropathyprogressionproteinsglt2 inhibitorstweakAlbuminsAlbuminuriaDiabetes mellitusDiabetes mellitus, type 2Diabetic kidney diseaseDiabetic nephropathiesDipeptidyl-peptidase iv inhibitorsGlucoseHumansInflammationKlothoRenal-diseaseSglt2 inhibitorsSodiumSodium-glucose transporter 2 inhibitorsSymporters

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal BIOMEDICINE & PHARMACOTHERAPY 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 22/278, thus managing to position itself as a Q1 (Primer Cuartil), in the category Pharmacology & Pharmacy. Notably, the journal is positioned above the 90th percentile.

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: 4.38. 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: 4.32 (source consulted: FECYT Feb 2024)
  • Field Citation Ratio (FCR) from Dimensions: 14.4 (source consulted: Dimensions Aug 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-08-02, the following number of citations:

  • WoS: 19
  • Scopus: 19
  • Europe PMC: 12

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 2025-08-02:

  • 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: 47.
  • 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: 54 (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: 15.4.
  • The number of mentions on the social network X (formerly Twitter): 27 (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/10486/713546

Leadership analysis of institutional authors

the author responsible for correspondence tasks has been SANCHEZ NIÑO, MARIA DOLORES.