Reducing oxidative stress stands at the center of a prevention and control strategy for mitigating cellular senescence and aging. Kidney disease is characterized by a premature aging syndrome, and to find a modulator targeting against oxidative stress, mitochondrial dysfunction, and cellular senescence in kidney cells could be of great significance to prevent and control the progression of this disease. This review focuses on the pathogenic mechanisms related to the appearance of oxidative stress damage and mitochondrial dysfunction in kidney disease. In this scenario, the anti-aging Klotho protein plays a crucial role by modulating signaling pathways involving the manganese-containing superoxide dismutase (Mn-SOD) and the transcription factors FoxO and Nrf2, known antioxidant systems, and other known mitochondrial function regulators, such as mitochondrial uncoupling protein 1 (UCP1), B-cell lymphoma-2 (BCL-2), Wnt/β-catenin, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1 alpha), transcription factor EB, (TFEB), and peroxisome proliferator-activated receptor gamma (PPAR-gamma). Therefore, Klotho is postulated as a very promising new target for future therapeutic strategies against oxidative stress, mitochondria abnormalities, and cellular senescence in kidney disease patients.

This study was designed to investigate the controversy on the potential role of sKlotho as an early biomarker in Chronic Kidney Disease–Mineral Bone Disorder (CKD-MBD), to assess whether sKlotho is a reliable marker of kidney α-Klotho, to deepen the effects of sKlotho on vascular smooth muscle cells (VSMCs) osteogenic differentiation and to evaluate the role of autophagy in this process. Experimental studies were conducted in CKD mice fed a normal phosphorus (CKD+NP) or high phosphorus (CKD+HP) diet for 14 weeks. The patients’ study was performed in CKD stages 2–5 and in vitro studies which used VSMCs exposed to non-calcifying medium or calcifying medium with or without sKlotho. The CKD experimental model showed that the CKD+HP group reached the highest serum PTH, P and FGF23 levels, but the lowest serum and urinary sKlotho levels. In addition, a positive correlation between serum sKlotho and kidney α-Klotho was found. CKD mice showed aortic osteogenic differentiation, together with increased autophagy. The human CKD study showed that the decline in serum sKlotho is previous to the rise in FGF23. In addition, both serum sKlotho and FGF23 levels correlated with kidney function. Finally, in VSMCs, the addition of sKlotho prevented osteogenic differentiation and induced autophagy. It can be concluded that serum sKlotho was the earliest CKD-MBD biomarker, a reliable indicator of kidney α-Klotho and that might protect against osteogenic differentiation by increasing autophagy. Nevertheless, further studies are needed to investigate the mechanisms of this possible protective effect.

Urinary albumin excretion is an established marker of cardiovascular (CV) risk in people with type 2 diabetes mellitus (T2DM). However, its prognostic significance within the normoalbuminuric range (< 30 mg/g) remains uncertain, particularly regarding sex-specific differences. This study examined whether urinary albumin-to-creatinine ratio (UACR; KDIGO A1 range) is associated with coronary artery disease (CAD) severity and 6-year major adverse cardiovascular events (MACE) in women and in men with T2DM and preserved kidney function (eGFR > 60 mL/min/1.73 m², UACR < 30 mg/g), treating sex differences as a co-primary objective. We conducted a retrospective cohort study involving adults with T2DM who underwent diagnostic coronary angiography. Baseline associations between log-transformed UACR, CAD severity, CV risk factors, and inflammatory markers were evaluated using multivariable linear regression. MACE (defined as non-fatal myocardial infarction or unstable angina requiring urgent revascularization, stroke, or CV death) were recorded during 6-year of follow-up. Cox proportional hazards models, adjusted for age, sex, hypertension, smoking, BMI, lipid profile, hs-CRP, and ACEI/ARB use, were used to assess UACR–MACE associations. We included 420 adults (180 women, 42.9%) with a mean of age 65.3 ± 10.7 years and a median UACR 7.56 mg/g (IQR 4.12–15.5). Significant CAD was present in 310 participants (73.8%), and 78 experienced MACE during follow-up (35.5%). Higher UACR was independently associated with greater coronary stenosis (adjusted R² = 0.090, p < 0.001). Kaplan-Meier analysis showed a significantly higher incidence of MACE in the highest UACR tertile (log-rank p = 0.039). In multivariable Cox models adjusted for age, sex, hypertension, smoking, lipid profile, hs-CRP, SSI, and ACEI/ARB use, higher log-UACR independently predicted MACE (adjusted HR 1.67, 95% CI 1.35–2.10; p < 0.01). In sex-stratified Cox models, higher log-UACR predicted MACE in both sexes and remained independently associated in multivariable analyses (adjusted HR 1.67, 95% CI 1.35–2.10; p < 0.01). Associations were directionally stronger in women, who showed higher cumulative event rates across UACR tertiles, although the formal UACR × sex interaction did not reach statistical significance. Within the normoalbuminuric range, UACR is associated with greater CAD burden and higher 6-year MACE risk, with sex-specific differences. These findings suggest potential sex-related variation in the prognostic value of high-normal albuminuria, particularly among women, warranting validation in larger and more diverse cohorts.

The success of hemodialysis (HD) treatments has been evaluated using objective measures of analytical parameters, or machine-measured parameters, despite having available validated instruments that assess patient perspective. There is an emerging interest regarding the use and relevance of patient-related outcomes (PROs). Electronic PROs (ePROs) involve the use of electronic technology, provide rapid access to this information, and are becoming more widely used in clinical trials and studies to evaluate efficacy and safety. Despite the scarce literature, this review suggests that ePROs are useful in providing a more customized and multidimensional approach to patient management and in making better clinical decisions in relevant aspects such as vascular access, duration and frequency of dialysis sessions, treatment of anemia, mental health, fatigue, and quality of life. The purpose of this review is to raise interest in the systematic use of ePROs in HD and to promote the development of studies in this field, which can respond to the gaps in knowledge and contribute to the implementation of the use of ePROs through new technologies, helping to improve the quality of health care.