Nemesis Alhelí Pineda Alfaro

Chronic kidney disease (CKD) without diabetes mellitus has become an increasingly recognized clinical entity whose progression cannot be explained exclusively by traditional hemodynamic mechanisms. Growing evidence indicates that endocrine dysregulation, metabolic remodeling, mitochondrial dysfunction, chronic inflammation, oxidative stress, and altered communication between the kidney and other organ systems play fundamental roles throughout disease development and progression. The present review critically analyzes current scientific evidence regarding the endocrine and metabolic mechanisms involved in non-diabetic CKD, integrating findings from nephrology, endocrinology, and internal medicine while incorporating information relevant to Latin American populations. A narrative review based on the Scientific Method was conducted using high-quality publications retrieved from internationally recognized databases and clinical practice guidelines. The available evidence demonstrates that persistent activation of the renin–angiotensin–aldosterone system, disruption of the fibroblast growth factor 23–Klotho axis, impaired vitamin D metabolism, insulin resistance, obesity-related endocrine alterations, mitochondrial dysfunction, and gut–kidney interactions contribute substantially to renal fibrosis, progressive loss of kidney function, and cardiovascular complications. Contemporary therapeutic approaches, particularly sodium–glucose cotransporter-2 inhibitors, have significantly modified disease management by providing nephroprotective effects beyond glycemic control. Emerging biomarkers and precision medicine strategies also show considerable potential for improving early diagnosis, individualized risk assessment, and targeted therapeutic interventions. Nevertheless, additional multicenter studies, particularly involving underrepresented regions such as Latin America, remain necessary to strengthen the current evidence base. Overall, non-diabetic CKD should be regarded as a complex multisystem disorder requiring an integrated clinical approach that combines endocrine, metabolic, cardiovascular, and nephrological perspectives to optimize patient outcomes.

Immune senescence has emerged as one of the principal biological mechanisms linking aging with the development and progression of autoimmune rheumatic diseases. Rather than representing a simple decline in immune function, aging induces profound remodeling of both innate and adaptive immunity, characterized by chronic low-grade inflammation, loss of immune tolerance, impaired cellular regeneration, mitochondrial dysfunction, telomere shortening, epigenetic alterations, and expansion of senescent immune-cell populations. The objective of this review was to analyze current evidence regarding the mechanisms through which immune senescence reshapes autoimmune rheumatic diseases and to examine its clinical implications, biomarkers, and emerging therapeutic strategies. A narrative literature review was conducted using the scientific method and included publications retrieved from PubMed/MEDLINE, Scopus, Web of Science, ScienceDirect, SpringerLink, Nature, Frontiers, and Wiley. The evidence consistently demonstrated that inflammaging, adaptive immune remodeling, and cellular senescence contribute to disease progression, increased susceptibility to infections, reduced vaccine responsiveness, cardiovascular complications, frailty, osteoporosis, sarcopenia, and diminished functional capacity. Conventional inflammatory biomarkers remain widely used; however, increasing attention has been directed toward multi-omics technologies, epigenetic clocks, mitochondrial biomarkers, proteomics, metabolomics, and immune-cell phenotyping for more accurate assessment of biological immune aging. Current therapeutic approaches continue to rely on disease-modifying antirheumatic drugs and biologic agents, while emerging interventions—including JAK inhibitors, mTOR modulation, senolytic therapies, microbiome-targeted strategies, and precision medicine—offer promising opportunities for future individualized management. Overall, immune senescence should be recognized as a fundamental component of autoimmune rheumatic diseases, providing important opportunities for improving diagnosis, risk stratification, therapeutic decision-making, and long-term clinical outcomes in aging populations.

Cardiovascular disease remains the leading cause of mortality worldwide despite substantial advances in lipid-lowering therapies. Although achieving recommended low-density lipoprotein cholesterol (LDL-C) targets significantly reduces cardiovascular risk, many patients continue to experience recurrent cardiovascular events, a phenomenon known as residual cardiovascular risk. Increasing evidence indicates that chronic low-grade inflammation is a major contributor to this persistent risk. This review analyzes current scientific evidence regarding the biological mechanisms, inflammatory biomarkers, and emerging therapeutic strategies associated with residual inflammatory risk beyond LDL cholesterol. The literature demonstrates that activation of the NLRP3 inflammasome and the interleukin-1β/interleukin-6 pathway plays a central role in endothelial dysfunction, plaque progression, and atherosclerotic instability. High-sensitivity C-reactive protein (hs-CRP) remains the most widely validated biomarker for identifying persistent inflammatory activity in clinical practice. Landmark clinical trials, including CANTOS, COLCOT, and LoDoCo2, have demonstrated that selective anti-inflammatory therapies reduce recurrent cardiovascular events independently of additional LDL-C lowering, whereas nonspecific anti-inflammatory approaches have shown limited benefit. Furthermore, obesity, type 2 diabetes mellitus, metabolic syndrome, and chronic kidney disease substantially amplify residual inflammatory risk through shared pathophysiological mechanisms. Current evidence supports a transition toward comprehensive cardiometabolic prevention integrating lipid management, lifestyle modification, metabolic optimization, and targeted anti-inflammatory therapy. Future precision medicine strategies incorporating inflammatory biomarkers and individualized risk assessment may further improve cardiovascular outcomes and reduce the global burden of atherosclerotic disease.

Metabolic syndrome is currently recognized as a major multisystem disorder associated with significant cardiovascular, renal, endocrine, and inflammatory complications. The present review aimed to analyze the pathophysiological mechanisms, epidemiological characteristics, cardiovascular and renal outcomes, and current therapeutic perspectives associated with metabolic syndrome through an integrative analysis of recent scientific literature. A narrative and integrative review methodology based on the Scientific Method and a Process-Based Approach was employed using peer-reviewed publications indexed in PubMed, Scopus, and internationally recognized medical journals. The analyzed evidence demonstrated that insulin resistance, visceral obesity, chronic low-grade inflammation, oxidative stress, endothelial dysfunction, and neurohormonal activation constitute the principal mechanisms underlying multisystem deterioration in metabolic syndrome. Cardiovascular complications including coronary artery disease, heart failure, hypertension, and cerebrovascular disease were strongly associated with metabolic dysfunction. Additionally, chronic kidney disease progression appeared closely linked to glomerular hyperfiltration, fibrosis, inflammatory injury, and endothelial impairment. Epidemiological findings from Mexico, Colombia, and Ecuador revealed increasing prevalence patterns associated with obesity, sedentary lifestyles, nutritional transition, and socioeconomic disparities. The review also identified the importance of multidisciplinary therapeutic strategies involving lifestyle modification, cardiovascular risk reduction, glycemic control, renal protection, and emerging pharmacological therapies such as GLP-1 receptor agonists and SGLT2 inhibitors. Overall, metabolic syndrome should be understood as a systemic cardiometabolic disorder requiring comprehensive clinical management, preventive medicine strategies, and continued scientific investigation to reduce long-term morbidity and mortality.