Angiopoietin as A Novel Prognostic Marker in Kidney Disease.

Renal injury is among the leading causes of morbidity and mortality, however, there are no reliable indicators for determining the likelihood of developing CKD, CKD progression or AKI events. Vascular growth factors called angiopoietins have a role in endothelial function, vascular remodeling, tissue stabilization and inflammation, and have been implicated as prognostic and predictive markers in AKI. Although the exact mechanism of the relationship between kidney injury and angiopoietins is unknown, this review demonstrates that AKI patients have higher angiopoietin-2 levels and that higher angiopoietin-1 to angiopoietin-2 ratio may potentially be linked with a reduced risk of the chronic kidney disease progression. This review therefore emphasizes the importance of angiopoietin-2 and proposes that it could be an important predictor of AKI in clinical settings. There is a need for further large scale randomized clinical trials in order to have a better understanding of the significance of angiopoietin-2 and for the determination of its potential clinical implications.

Is there any robust evidence showing that SGLT2 inhibitor predisposes to cancer?

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.

Physical exercise in kidney disease: A commonly undervalued treatment modality.

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.

Kidney and liver fat accumulation: from imaging to clinical consequences.

BACKGROUND: Recent studies indicate that accumulation of adipose tissue in various organs such as liver and kidney may contribute to the pathophysiology of metabolic syndrome. We aim to investigate the association between kidney and liver adipose tissue accumulation, assessed by the magnetic resonance imaging (MRI) proton density fat fraction technique, along with its relation to clinical and biochemical parameters. METHODS: We included 51 volunteers with phenotypical features of metabolic syndrome (mean age = 34 years, mean body-mass index = 26.4 kg/m2) in our study in which liver and kidney adipose tissue accumulation was assessed via MRI-proton density fat fraction along with multiple other clinical and biochemical parameters such as estimated glomerular filtration rate (eGFR), urine albumin-to-creatinine ratio, serum lipid profile, liver function tests and body-mass index (BMI). RESULTS: Our results from the univariate linear regression analysis indicate that both the kidney and liver scores were positively correlated with markers such as BMI, urine albumin-to-creatinine ratio, triglycerides (p < 0.001) and negatively correlated with eGFR (p < 0.05). In multivariate analysis, urine albumin-to-creatinine ratio (p < 0.05), triglycerides (p < 0.01), eGFR (p < 0.05) and BMI (p < 0.001) were found to be independently associated with kidney and liver fat accumulation, respectively (R2 = 0.64; R2 = 0.89). There was also a positive correlation between kidney and liver fat accumulation. CONCLUSION: We have found a significant association between adipose tissue accumulation in liver and kidney and the parameters of metabolic syndrome. Moreover, the presence of a strong association between kidney and liver fat accumulation and kidney function parameters such as urine albumin-to-creatinine ratio and eGFR may be an indicator of the clinical significance of parenchymal fat accumulation.

Intrauterine life to adulthood: a potential risk factor for chronic kidney disease.

Multiple risk factors for chronic kidney disease (CKD), one of the major causes of morbidity and mortality in the adult population globally, have been identified, including older age, male gender, family history, smoking, diabetes mellitus, hypertension, ischaemic heart diseases and various medications. Preterm delivery, affecting >10% of the newborns in the USA, is a global concern with increasing incidence in recent decades. Preterm birth has been linked to multiple medical comorbidities such as diabetes mellitus, hypertension and cardiovascular diseases, while its association with CKD has recently been investigated. Prematurity and intrauterine growth restriction (IUGR) have been associated with an increased risk for CKD, specific histopathological examination findings and CKD-associated risk factors such as diabetes mellitus, hypertension and dyslipidaemia. In this narrative review, our aim is to evaluate and summarize the association between the risk for CKD and prematurity, low birthweight and IUGR along with potential underlying pathophysiological mechanisms.

An update review on hemodynamic instability in renal replacement therapy patients.

BACKGROUND: Hemodynamic instability in patients undergoing kidney replacement therapy (KRT) is one of the most common and essential factors influencing mortality, morbidity, and the quality of life in this patient population. METHOD: Decreased cardiac preload, reduced systemic vascular resistance, redistribution of fluids, fluid overload, inflammatory factors, and changes in plasma osmolality have all been implicated in the pathophysiology of hemodynamic instability associated with KRT. RESULT: A cascade of these detrimental mechanisms may ultimately cause intra-dialytic hypotension, reduced tissue perfusion, and impaired kidney rehabilitation. Multiple parameters, including dialysate composition, temperature, posture during dialysis sessions, physical activity, fluid administrations, dialysis timing, and specific pharmacologic agents, have been studied as possible management modalities. Nevertheless, a clear consensus is not reached. CONCLUSION: This review includes a thorough investigation of the literature on hemodynamic instability in KRT patients, providing insight on interventions that may potentially minimize factors leading to hemodynamic instability.

The risk for chronic kidney disease in metabolically healthy obese patients: A systematic review and meta-analysis.

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.

Kidney replacement therapy patients with COVID-19 in the vaccine era: what do we need to know?

Kidney disease is one of the most important factors affecting the prognosis of patients with coronavirus disease 2019 (COVID-19). Patients on kidney replacement therapy (KRT; dialysis and kidney transplant recipients) are vulnerable to severe complications of COVID-19. As the pandemic evolves and preventive strategies, availability of healthcare facilities, treatment approaches and vaccination strategies change, studies are needed on COVID-19 epidemiology and outcomes in KRT patients that contribute to vaccination regimens, treatment protocols and immunosuppressive therapies of KRT patients with COVID-19. In their registry-based study, Quiroga et al. analyzed COVID-19 KRT patients in Spain across six pandemic waves in order to evaluate dynamic treatment approaches and outcomes as well as the efficacy of vaccination.

A promising tool: triglyceride-glucose index to stratify the risk of cardiovascular events in chronic kidney disease.

Lipid profile management is one of the crucial components to optimize outcomes in patients with chronic kidney disease (CKD). CKD is associated with poor cardiovascular outcomes due to both a direct cardiovascular impact of CKD and the presence of metabolic comorbidities. Low-density lipoprotein cholesterol is the main target of current lipid-lowering drugs. However, the derangement of lipid metabolism in CKD is more complex. The recently described triglyceride-glucose index (TyG) is associated with cardiovascular outcomes in the general population. In recent studies, the TyG was associated with CKD progression in CKD patients and with cardiovascular death in patients on peritoneal dialysis. Quiroga et al. now show that the TyG is associated with the occurrence of major cardiovascular events in individuals free from diabetes with non-dialysis-dependent CKD.

The role of body mass index on IgA nephropathy prognosis: a systematic review and meta-analysis.

BACKGROUND: Recent studies show that obese patients have worse outcomes in IgA nephropathy as compared to normal weight patients. MATERIALS AND METHODS: We performed a systematic review and meta-analysis of prospective, retrospective, randomized and nonrandomized studies, which studied the impact of obesity or high body mass index (BMI) on different parameters of IgA nephropathy prognosis and outcome. We searched through PubMed, Ovid/Medline, Web of Science, and the Cochrane Central Register of Controlled Trials (Wiley). RESULTS: We included 16 studies in our final analysis with a total of 4258 patients. Overall, there was a significantly lower estimated glomerular filtration rate (eGFR) in IgA nephropathy patients with BMI in the overweight/obese range than in those with normal BMI (mean difference 6.01, 95% CI 2.78-9.24 ml/min/1.73 m2, P < 0.001), but no significant difference in serum creatinine or proteinuria levels. No studies measured GFR. There were contradictory results regarding the relationship between BMI and blood pressure, histological parameters or outcomes in patients with IgA nephropathy. CONCLUSIONS: Higher BMI in IgA nephropathy patients might be associated with lower kidney function, but this should be confirmed by measuring GFR. Evidence regarding other kidney damage parameters and outcomes is inconclusive.

Substitution of Sugar-Sweetened Beverages for Other Beverages: Can It Be the Next Step Towards Healthy Aging?

PURPOSE OF REVIEW: With the prolongation of life expectancy, the gap between lifespan and "health span," the disease-free lifespan, has been widening due to the massive burden of age-related chronic diseases and research on healthy aging has been gaining momentum. A growing body of evidence suggests that diet is a strong determinant of healthy aging and consumption of sugar-sweetened beverages (SSB), a major source of added sugars, predicts poor health outcomes in the aging population, including cardiovascular disease, diabetes, and cancer. Evidence further supports a link between sugar-sweetened beverages-triggered pathological processes and biologic factors of aging, including inflammaging, oxidative stress, and alterations in intestinal microbiota. At present, substitution of sugar-sweetened beverages with healthier alternative beverage remains the most robust strategy to limit the deleterious effects of sugar-sweetened beverages on health worldwide and may help achieve healthy longevity. The purpose of this review is to provide an overview of mechanisms by which sugar-sweetened beverages consumption may impact the physiological aging process and how a simple intervention of beverage replacement may promote healthy aging. RECENT FINDINGS: Recent findings indicate that SSB are associated with accelerated aging phenotype and activate various adverse biological processes such as chronic inflammation, oxidative stress, insulin resistance, and gut dysbiosis. Replacing SSB with healthier beverages may be a reasonable option to reduce the burden of chronic disease in the aging population and even prolong life and healthspan.