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Pentoxifylline ameliorates subclinical atherosclerosis progression in patients with type 2 diabetes and chronic kidney disease: a randomized pilot trial.
Donate-Correa, Javier; Ferri, Carla M; Mora-Fernández, Carmen; Pérez-Delgado, Nayra; González-Luis, Ainhoa; Navarro-González, Juan F.
Afiliación
  • Donate-Correa J; Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain. jdonatecorrea@gmail.com.
  • Ferri CM; GEENDIAB (Grupo Español para el estudio de la Nefropatía Diabética), Sociedad Española de Nefrología, Santander, Spain. jdonatecorrea@gmail.com.
  • Mora-Fernández C; RICORS2040 (RD21/0005/0013), Instituto de Salud Carlos III, 28000 Madrid, Madrid, Spain. jdonatecorrea@gmail.com.
  • Pérez-Delgado N; Instituto de Tecnologías Biomédicas, Universidad de La Laguna, Santa Cruz de Tenerife, Spain. jdonatecorrea@gmail.com.
  • González-Luis A; Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain.
  • Navarro-González JF; Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain.
Cardiovasc Diabetol ; 23(1): 314, 2024 Aug 24.
Article en En | MEDLINE | ID: mdl-39182114
ABSTRACT

BACKGROUND:

Diabetic kidney disease (DKD) is associated with a higher risk of cardiovascular disease (CVD). Pentoxifylline (PTF), a nonselective phosphodiesterase inhibitor with anti-inflammatory, antiproliferative, and antifibrotic actions, has demonstrated renal benefits in both clinical trials and meta-analyses. The present work aimed to study the effects of PTF on the progression of subclinical atherosclerosis (SA) in a population of patients with diabetes and moderate to severe chronic kidney disease (CKD).

METHODS:

In this open-label, randomized controlled, prospective single-center pilot study the evolution of carotid intima-media thickness (CIMT) and ankle-brachial index (ABI) were determined in 102 patients with type 2 diabetes mellitus and CKD assigned to PTF, aspirin or control groups during 18 months. We also determined the variations in the levels of inflammatory markers and Klotho (KL), a protein involved in maintaining cardiovascular health, and their relationship with the progression of SA.

RESULTS:

Patients treated with PTF presented a better evolution of CIMT, increased KL mRNA levels in peripheral blood cells (PBCs) and reduced the inflammatory state. The progression of CIMT values was inversely related to variations in KL both in serum and mRNA expression levels in PBCs. Multiple regression analysis demonstrated that PTF treatment and variations in mRNA KL expression in PBCs, together with changes in HDL, were significant determinants for the progression of CIMT (adjusted R2 = 0.24, P < 0.001) independently of traditional risk factors. Moreover, both variables constituted protective factors against a worst progression of CIMT [OR 0.103 (P = 0.001) and 0.001 (P = 0.005), respectively].

CONCLUSIONS:

PTF reduced SA progression assessed by CIMT variation, a beneficial effect related to KL gene expression in PBCs. TRIAL REGISTRATION The study protocol code is PTF-AA-TR-2009 and the trial was registered on the European Union Drug Regulating Authorities Clinical Trials (EudraCT #2009-016595-77). The validation date was 2010-03-09.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pentoxifilina / Progresión de la Enfermedad / Diabetes Mellitus Tipo 2 / Insuficiencia Renal Crónica / Grosor Intima-Media Carotídeo Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Cardiovasc Diabetol Asunto de la revista: ANGIOLOGIA / CARDIOLOGIA / ENDOCRINOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: España Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pentoxifilina / Progresión de la Enfermedad / Diabetes Mellitus Tipo 2 / Insuficiencia Renal Crónica / Grosor Intima-Media Carotídeo Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Cardiovasc Diabetol Asunto de la revista: ANGIOLOGIA / CARDIOLOGIA / ENDOCRINOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: España Pais de publicación: Reino Unido