dianas 14(1) > Ortiz etal

dianas | Vol 14 Num 1 | marzo 2025 | e202503x011

Chronic Kidney Disease and Pathological Aging: The Central Role of the Complement System.

María Gabriela Ortiz^a, María del Mar Rodríguez, David Serrano, Gemma Valera, Julia Carracedo, Natalia Guerra, Rafael Ramírez

Facultad de CC. Biológicas, Universidad Complutense de Madrid (UCM).

a. maorti11@ucm.es; mariagabrielaortizdiaz@gmail.com

X Congreso de Señalización Celular, SECUAH 2024.
XIX Simposio de Dianas Terapéuticas.
17 a 21 de marzo, 2025. Universidad de Alcalá. Alcalá de Henares, Madrid. España.

Keywords: Chronic Kidney Disease (CKD); Complement System (CS); Senescence-Associated Secretory Phenotype (SASP); Cellular Senescence; Inflammation

Abstract

Chronic kidney disease (CKD) constitutes a pathological condition characterized by persistent inflammation and the activation of the senescence-associated secretory phenotype (SASP), thereby contributing to pathological aging. Although the molecular mechanisms linking these processes remain insufficiently detailed, this study identifies the Complement System (CS), a key pathway of innate immunity, as a fundamental driver of CKD progression and its impact on cellular senescence. To investigate this, blood samples from 179 CKD patients and 18 healthy individuals from the Hospital 12 de Octubre were analyzed. Using Luminex® xMAP® and ELISA technologies, various SASP-associated molecules and key CS markers were quantified in plasma, enabling a detailed evaluation of their role in CKD progression. The results revealed elevated levels of CS molecules, cytokines, chemokines, and proteases in patients with advanced CKD, particularly in those undergoing peritoneal dialysis or hemodialysis treatments. However, these concentrations normalized in transplanted patients, suggesting a partial reversal of the pro-inflammatory state following kidney transplantation. Overall, these findings highlight the overexpression of CS and SASP markers in advanced CKD stages, as well as their potential modulation after transplantation. Consequently, kidney transplantation emerges as a key therapeutic strategy to counteract the chronic inflammation associated with CKD. Furthermore, CS and SASP molecules could serve as valuable biomarkers for CKD diagnosis and prognosis, as well as potential therapeutic targets to mitigate its pathological effects.