Cardiovascular kidney metabolic (CKM) syndrome represents a complex interplay of cardiovascular disease (CVD), chronic kidney disease (CKD), and metabolic comorbidities, posing a significant public health challenge. Gender exerts a critical influence on CKM syndrome, affecting the disease severity and onset through intricate interactions involving sex hormones and key physiological pathways such as the renin–angiotensin system, oxidative stress, inflammation, vascular disease and insulin resistance. It is widely known that beyond the contribution of traditional risk factors, men and women exhibit significant differences in CKM syndrome and its components, with distinct patterns observed in premenopausal women and postmenopausal women compared to men. Despite women generally experiencing a lower incidence of CVD, their outcomes following cardiovascular events are often worse compared to men. The disparities also extend to the treatment approaches for kidney failure, with a higher prevalence of dialysis among men despite women exhibiting higher rates of CKD. The impact of endogenous sex hormones, the correlations between CKM and its components, as well as the long-term effects of treatment modalities using sex hormones, including hormone replacement therapies and gender-affirming therapies, have drawn attention to this topic. Current research on CKM syndrome is hindered by the scarcity of large-scale studies and insufficient integration of gender-specific considerations into treatment strategies. The underlying mechanisms driving the gender disparities in the pathogenesis of CKM syndrome, including the roles of estrogen, progesterone and testosterone derivatives, remain poorly understood, thus limiting their application in personalized therapeutic interventions. This review synthesizes existing knowledge to clarify the intricate relationship between sex hormones, gender disparities, and the progression of CVD within CKM syndrome. By addressing these knowledge gaps, this study aims to guide future research efforts and promote tailored approaches for effectively managing CKD syndrome.

Stress, encompassing psychological, physical, and physiological challenges, is an important factor affecting an individual's well-being and potentially leading to psychiatric, neurodegenerative, immune, and metabolic disorders. However, not everyone exposed to stress develops these conditions, highlighting the concept of resilience. Resilience is a dynamic process categorized into four dimensions: pre-existing resilience capacity, ongoing resilience processes, post-stress resilience outcomes, and recovery from psychopathologies. These dimensions involve genomic, cellular, and systemic interactions influenced by genetic factors, early life experiences, adult life experiences in addition to community/environmental factors, and health behaviors. The biological response to stress encompasses endocrine, autonomic, immunological, and behavioral components, modulated by stressor characteristics and individual traits. Due to the limitations in studying stress and resilience in humans, translational models using rodents and cell cultures are essential. Rodent models include acute, chronic, and traumatic stress paradigms, aiding the study of stress-related behavioral and molecular outcomes. Additionally, early life stress models, such as prenatal stress and maternal separation, provide insights into developmental impacts. In this review, first, rodent models for lifelong stress exposure will be summarized considering their validity, advantages, and limitations. Subsequently, an overview of models designed to enhance resilience capacity and process in rodents, and later the behavioral models employed to study the outcomes of resilience will be given. Lastly, the focus will be shifted to cell culture and iPSCs models. Finally, future considerations focused on improving translational models used to study stress and resilience will be discussed. It is aimed to provide an overview of designs for translational stress and resilience models to access more effective translational biomarkers associated with stress and resilience. Stress and resilience are complex phenomena influenced by various factors, spanning molecular to behavioral levels. Integrating data across dimensions remains crucial for unraveling the complexities of stress-related disorders and resilience.

Obesity poses a significant and growing risk factor for chronic kidney disease (CKD), requiring comprehensive evaluation and management strategies. This review explores the intricate relationship between obesity and CKD, emphasizing the diverse phenotypes of obesity, including sarcopenic obesity and metabolically healthy versus unhealthy obesity, and their differential impact on kidney function. We discuss the epidemiological evidence linking elevated body mass index (BMI) with CKD risk while also addressing the paradoxical survival benefits observed in obese CKD patients. Various measures of obesity, such as BMI, waist circumference, and visceral fat assessment, are evaluated in the context of CKD progression and outcomes. Mechanistic insights into how obesity promotes renal dysfunction through lipid metabolism, inflammation, and altered renal hemodynamics are elucidated, underscoring the role of adipokines and the renin–angiotensin–aldosterone system. Furthermore, the review examines current strategies for assessing kidney function in obese individuals, including the strengths and limitations of filtration markers and predictive equations. The management of obesity and associated comorbidities like arterial hypertension, type 2 diabetes mellitus, and non-alcoholic fatty liver disease in CKD patients is discussed. Finally, gaps in the current literature and future research directions aimed at optimizing the management of obesity-related CKD are highlighted, emphasizing the need for personalized therapeutic approaches to mitigate the growing burden of this intertwined epidemic.