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Background: The exact pathophysiological mechanisms of SGLT‐2 inhibitors in the development, progression or treatment of malignancies are not fully understood, but multiple hypotheses have been proposed. SGLT‐2 inhibitors have potential anti‐proliferative roles due to several underlying pathophysiological mechanisms, such as inhibition of ATP production, activation of AMPK signalling, induction of apoptosis and ferroptosis, inhibition of glutamate dehydrogenase activity and inhibition of DNA and RNA synthesis. However, heterogeneity among tumour cells and SGLT‐2 inhibitor drugs limit the generalizability of pre‐clinical studies. Methods: This is a narrative review discussing the potential anti‐cancer effects of SGLT‐2 inhibitors, an oral glucose‐lowering medication used in patients with type II diabetes mellitus. This review discusses underlying mechanisms, pre‐clinical and clinical trial data, epidemiological data and future perspectives on the use of SGLT‐2 inhibitors in cancer treatment. Results: Type II diabetes is linked to various comorbidities and malignancies, but some glucose‐slowering medications may have a preventive role in cancer. The use of SGLT‐2 inhibitors was associated with bladder cancer based on mice studies. However, meta‐analyses showed no significant increase in overall malignancy incidence of any specific type, except for empagliflozin and bladder cancer association. SGLT‐2 inhibitors can potentially reduce the heart damage caused by doxorubicin and sunitinib, while enhancing the anti‐cancer effects of doxorubicin. Combining SGLT‐2 inhibitors with doxorubicin may allow higher doses of chemotherapy use. Multiple ongoing clinical trials are investigating the potential therapeutic potential of SGLT‐2 inhibitors in various types of cancer. Conclusion: More large‐scale pre‐clinical and clinical studies are needed to explore their potential preventive and therapeutic roles of SGLT‐2 inhibitors in cancer treatment. In this narrative review, our aim is to explore the pre‐clinical and clinical data regarding the potential anti‐cancer effects of SGLT‐2 inhibitors including the hypothetical pathophysiological mechanisms. [ABSTRACT FROM AUTHOR]

Background: Physical inactivity has been identified as a risk factor for multiple disorders and a strong association exists between chronic kidney disease (CKD) and a sedentary lifestyle. Even though physical activity is crucial in the development and progression of disease, the general focus of the current medical practice is the pharmacological perspective of diseases with inadequate emphasis on lifestyle intervention. Methods: In this narrative review we explain the pathophysiological mechanisms underlying the beneficial effects of physical exercise on CKD in addition to discussing the clinical studies and trials centred on physical exercise in patients with CKD. Results: Physical activity influences several pathophysiological mechanisms including inflammation, oxidative stress, vascular function, immune response and macromolecular metabolism. While exercise can initially induce stress responses like inflammation and oxidative stress, long‐term physical activity leads to protective countermeasures and overall improved health. Trials in pre‐dialysis CKD patients show that exercise can lead to reductions in body weight, inflammation markers and fasting plasma glucose. Furthermore, it improves patients' functional capacity, cardiorespiratory fitness and quality of life. The effects of exercise on kidney function have been inconsistent in these trials. In haemodialysis, peritoneal dialysis and kidney transplant patients exercise interventions improve cardiorespiratory fitness, walking capacity and quality of life. Combined training shows the best performance to increase peak oxygen uptake in haemodialysis patients. In kidney transplant recipients, exercise improves walking performance, quality of life and potentially arterial stiffness. However, exercise does not affect glucose metabolism, serum cholesterol and inflammation biomarkers. Long‐term, adequately powered trials are needed to determine the long‐term feasibility, and effects on quality of life and major clinical outcomes, including mortality and cardiovascular risk, in all CKD stages and particularly in kidney transplant patients, a scarcely investigated population. Conclusion: Physical exercise plays a crucial role in ameliorating inflammation, oxidative stress, vascular function, immune response and macromolecular metabolism, and contributes significantly to the quality of life for patients with CKD, irrespective of the treatment and stage. Its direct impact on kidney function remains uncertain. Further extensive, long‐term trials to conclusively determine the effect of exercise on major clinical outcomes such as mortality and cardiovascular risk remain a research priority. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) is associated with obesity and metabolic syndrome. Nevertheless, the association of CKD with phenotype referred as metabolically healthy obese or overweight is unclear. In this this systematic review and meta‐analysis, we investigate the relationships between obesity and CKD independent of metabolic syndrome by appraising published evidence in studies focusing on metabolically healthy obese people. Materials and Methods: We performed a literature search through three databases Embase (Elsevier), the Cochrane Central Register of Controlled Trials (Wiley) and PubMed/Medline Web of Science up to March 2022 with the following terms: "chronic kidney disease", "kidney function", "obesity", "metabolic syndrome", "metabolically healthy obesity", "metabolically healthy overweight". Metabolically unhealthy was defined an individual having at least 3 of the following: abdominal obesity, high blood pressure, hypertriglyceridemia, low HDL cholesterol and hyperglycaemia. We used Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) for reporting. Prospective, retrospective, randomized and nonrandomized studies fitting the search criteria were included in our results. Results: Our final analysis included 16 studies with a total number of 4.965.285 participants. There is considerable heterogeneity in terms of study design, participant characteristics and number of participants across individual studies. In comparison to healthy normal weight patients, the risk was progressively higher in overweight (RR 1.29, 95% CI 1.27 to 1.32, p < 0.001) and obese patients (RR 1.47, 95% CI 1.31 to 1.65, p < 0.001). Conclusion: Metabolically healthy overweight and obese individuals have higher risk of CKD compared to individuals without weight excess. [ABSTRACT FROM AUTHOR]