Sexual dimorphism is a key factor to consider in the ageing process given the impact that it has on life expectancy. The oxidative-inflammatory theory of ageing states that the ageing process is the result of the establishment of oxidative stress which, due to the interplay of the immune system, translates into inflammatory stress, and that both processes are responsible for the damage and loss of function of an organism. We show that there are relevant gender differences in a number of oxidative and inflammatory markers and propose that they may account for the differential lifespan between sexes, given that males display, in general, higher oxidation and basal inflammation. In addition, we explain the significant role of circulating cell-free DNA as a marker of oxidative damage and an inductor of inflammation, connecting both processes and having the potential to become a useful ageing marker. Finally, we discuss how oxidative and inflammatory changes take place differentially with ageing in each sex, which could also have an impact on the sex-differential lifespan. Further research including sex as an essential variable is needed to understand the grounds of sex differences in ageing and to better comprehend ageing itself.

Oxidative stress plays a key role in the pathophysiology of chronic kidney disease (CKD). Most studies have investigated peripheral redox state focus on plasma, but not in different immune cells. Our study analyzed several redox state markers in plasma and isolated peripheral polymorphonuclear (PMNs) and mononuclear (MNs) leukocytes from advanced-CKD patients, also evaluating differences of hemodialysis (HD) and peritoneal dialysis (PD) procedures. Antioxidant (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH)) and oxidant parameters (xanthine oxidase (XO), oxidized glutathione (GSSG), malondialdehyde (MDA)) were assessed in plasma, PMNs and MNs from non-dialysis-dependent-CKD (NDD-CKD), HD and PD patients and healthy controls. Increased oxidative stress and damage were observed in plasma, PMNs and MNs from NDD-CKD, HD and PD patients (increased XO, GSSG and MDA; decreased SOD, CAT, GPX and GSH; altered GSSG/GSH balance). Several oxidative alterations were more exacerbated in PMNs, whereas others were only observed in MNs. Dialysis procedures had a positive effect on preserving the GSSG/GSH balance in PMNs. Interestingly, PD patients showed greater oxidative stress than HD patients, especially in MNs. The assessment of redox state parameters in PMNs and MNs could have potential use as biomarkers of the CKD progression.

Chronic kidney disease (CKD) is associated with a high incidence of cardiovascular disease (CVD) due to the accumulation of uremic toxins, altered redox state, and chronic systemic inflammation. This study aimed to analyze the relationship between the redox status of patients with CKD and the phenotype of microvesicles (MVs) subtypes, and cardiovascular events. The oxidative stress level of each participant was determined using an individualized OXY-SCORE. The relationship between pro-oxidant and antioxidant parameters and the expression of membrane markers in endothelial-derived microvesicles (EMVs) and platelet-derived microvesicles (PMVs) was established. Patients with advanced CKD (ACKD) and hemodialysis (HD) had a higher OXY-SCORE than healthy subjects (HS), whereas peritoneal dialysis (PD) patients had similar scores to HS. PD patients showed elevated PMVs and CD41 expression, whereas HD patients had higher EMVs and CD31 expression. Patients with ACKD had higher tissue factor (TF) expression in the PMVs and EMVs. TF expression was correlated with xanthine oxidase (XO) activity and was negatively correlated with antioxidant parameters. Patients with cardiovascular events show elevated TF. In conclusion, microvesicles and oxidative stress may serve as markers of cardiovascular risk in CKD, with TF expression in PMVs and EMVs being potential predictive and prognostic biomarkers of CVD.

Chronic kidney disease is closely associated with an increased risk of cardiovascular disease. Although kidney transplantation represents the treatment of choice for patients with end-stage chronic kidney disease, it is also linked to significant cardiovascular risk. This study aimed to evaluate the relationship between cardiovascular pathology and oxidative status in kidney transplant recipients, while also assessing the influence of disease etiology and humoral immune response on oxidative imbalance. A cross-sectional analysis was conducted in individuals with advanced chronic kidney disease (n = 36) and kidney transplant recipients (n = 40). A total of 18 healthy subjects were included. The enzymatic activities of xanthine oxidase, superoxide dismutase, and glutathione peroxidase, and levels of lipid peroxidation products, oxidized glutathione, and reduced glutathione were measured using spectrophotometry in plasma and mononuclear and polymorphonuclear leukocytes isolated using Ficoll density gradients. Individual oxidative status was evaluated using OXYSCORE. Kidney transplantation was associated with a higher incidence of cardiovascular disease (p < 0.01) and increased levels of both prooxidant (p < 0.01) and antioxidant parameters (p < 0.01). Elevated OXYSCORE values were observed particularly in patients with nephroangiosclerosis, diabetic kidney disease, polycystic kidney disease (p < 0.05), and cardiovascular comorbidities (p < 0.001). Additionally, the presence of anti-graft antibodies correlated with higher oxidative scores. These findings suggest that OXYSCORE may serve as a potential indicator of cardiovascular damage in kidney transplant recipients.

Background/Objectives: Patients with chronic kidney disease (CKD) face higher risks of infections, poor vaccine responses, and cardiovascular diseases, leading to increased morbidity and mortality due to immune dysfunction and frailty. This study aims to evaluate immune status and frailty in CKD patients across different treatments, examine the influence of frailty on immune status, and link these factors to mortality. Methods: A total of 174 participants were included (end-stage renal disease, ESRD n = 40; hemodialysis, HD n = 40; peritoneal dialysis, n = 36; kidney transplant patients, n = 40; healthy subjects n = 18). Immunophenotyping of lymphocyte and monocyte subpopulations was performed, and frailty was assessed using the Edmonton Frail Scale. Principal component analysis (PCA) integrated immune and frailty variables to define an “immuno-fragile profile,” and survival was monitored for up to six years. Results: CKD patients, especially those on HD, showed decreased lymphocyte counts and proinflammatory monocyte subpopulations with increased expression of costimulatory molecules (B7.2/CD86 and ICAM-1/CD54). Frailty was most prevalent in HD patients (53%), with notable sex differences. PCA identified three components—lymphocyte counts, monocyte co-stimulatory expression, and frailty—that together explained 70% of the variance. Survival analysis revealed that patients with lower lymphocyte counts and higher frailty scores had increased mortality risk, especially in the HD and ESRD groups. Cox regression confirmed that the immuno-fragile profile independently predicted mortality. Conclusions: The integration of immune alterations and frailty defines an immuno-fragile profile strongly associated with mortality in CKD patients, which may serve as a robust prognostic tool to improve risk stratification and guide personalized interventions in clinical practice.