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.

Mineralocorticoid receptor antagonists in kidney transplantation.

BACKGROUND: The fundamental role of the renin-angiotensin-aldosterone system in the pathophysiology of chronic kidney disease, congestive heart failure, hypertension and proteinuria is well established in pre-clinical and clinical studies. Mineralocorticoid receptor antagonists are among the primary options for renin-angiotensin-aldosterone system blockage, along with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. METHODS: In this narrative review, we aim to evaluate the efficiency and safety of mineralocorticoid receptor antagonists in kidney transplant recipients, including the potential underlying pathophysiology. RESULTS: The efficiency and safety of mineralocorticoid receptor antagonists in managing chronic kidney disease and proteinuria, either non-nephrotic or nephrotic range, have been demonstrated among nontransplanted patients, though studies investigating the role of mineralocorticoid receptor antagonists among kidney transplant recipients are scarce. Nevertheless, promising results have been reported in pre-clinical and clinical studies among kidney transplant recipients regarding the role of mineralocorticoid receptor antagonists in terms of ischaemia-reperfusion injury, proteinuria, or calcineurin inhibitor-mediated nephrotoxicity without considerable adverse events such as hypotension, hyperkalaemia or worsening renal functions. CONCLUSION: Even though initial results regarding the role of mineralocorticoid receptor antagonist therapy for kidney transplant recipients are promising, there is clear need for large-scale randomized clinical trials with long-term follow-up data.

Unveiling the intricacies of chronic kidney disease: From ocular manifestations to therapeutic frontiers.

BACKGROUND: Shared anatomical, histological and physiological pathways between the kidney and the eye are well documented, demonstrating that ocular manifestations serve as valuable prognostic indicators in chronic kidney disease (CKD), providing insights into disease severity and progression. Through non-invasive imaging modalities such as retinal fundus photography, early retinal microvascular alterations indicative of CKD progression can be detected, enabling timely intervention and risk stratification. However, the conclusions drawn from the review primarily demonstrate a strong or independent association between glaucoma or retinopathy and CKD. RESULTS AND CONCLUSION: Multiple shared pathophysiological events have been implicated in the pathogenesis in the alterations at eye and kidney including renin-angiotensin-aldosterone system. Patients with CKD are more likely to experience glaucoma, age-related macular degeneration, cataracts, uremic optic neuropathy and retinopathy. To establish the role of ocular manifestations in predicting CKD progression, it is crucial to address the limitations of correlation and explore the underlying causality with further research on common disease pathogenesis. Additionally, specific methods for risk stratification based on retinal changes, the effectiveness of timely interventions, and the development of predictive tools combining ocular and renal data are of utmost importance research topics to enlighten the bidirectional causality.

Tubular toxicity of proteinuria and the progression of chronic kidney disease.

Proteinuria is a well-established biomarker of chronic kidney disease (CKD) and a risk predictor of associated disease outcomes. Proteinuria is also a driver of CKD progression toward end-stage kidney disease. Toxic effects of filtered proteins on proximal tubular epithelial cells enhance tubular atrophy and interstitial fibrosis. The extent of protein toxicity and the underlying molecular mechanisms responsible for tubular injury during proteinuria remain unclear. Nevertheless, albumin elicits its toxic effects when degraded and reabsorbed by proximal tubular epithelial cells. Overall, healthy kidneys excrete over 1000 individual proteins, which may be potentially harmful to proximal tubular epithelial cells when filtered and/or reabsorbed in excess. Proteinuria can cause kidney damage, inflammation and fibrosis by increasing reactive oxygen species, autophagy dysfunction, lysosomal membrane permeabilization, endoplasmic reticulum stress and complement activation. Here we summarize toxic proteins reported in proteinuria and the current understanding of molecular mechanisms of toxicity of proteins on proximal tubular epithelial cells leading to CKD progression.

Glomerular hyperfiltration as a therapeutic target for CKD.

The global burden of chronic kidney disease (CKD) is high and increasing. Early diagnosis and intervention are key to improve outcomes. Single-nephron glomerular hyperfiltration is an early pathophysiologic manifestation of CKD that may result in absolute glomerular hyperfiltration, i.e. a high glomerular filtration rate (GFR), or be associated with normal or low GFR because of nephron loss (relative glomerular hyperfiltration). Even though compensatory glomerular hyperfiltration may contribute to maintain kidney function after the loss of kidney mass, the associated increased glomerular capillary pressure and glomerular and podocyte size drive podocyte loss, albuminuria and proximal tubular overload, contributing to CKD progression. In this regard, all kidney protective drugs in clinical use so far, from renin-angiotensin system blockers to mineralocorticoid receptor blockers to sodium-glucose co-transporter 2 inhibitors to tolvaptan, induce an early dip in glomerular filtration that is thought to represent reversal of hyperfiltration. As glomerular hyperfiltration may be present early in the course of kidney disease, its recognition may provide an effective intervention window that may predate current criteria based on high albuminuria or loss of GFR. Nevertheless, there is no diagnostic method with high sensitivity and specificity to identify single-nephron glomerular hyperfiltration, except when it leads to obvious absolute glomerular hyperfiltration, as observed in the early stages of diabetic kidney disease when nephron mass is still preserved. We now review the concept of glomerular hyperfiltration as an indicator of CKD risk, including definitions, challenges in diagnosis and evaluation, underlying pathophysiological mechanisms, potential therapeutic approaches and unanswered questions.

A commentary from the European Renal Best Practice (ERBP) on the Kidney Disease Improving Global Outcomes (KDIGO) 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease in children and adults.

The Kidney Disease: Improving Global Outcomes (KDIGO) 2024 Guidelines for identification and management of chronic kidney disease (CKD) are a welcome development coming 12 years after the paradigm changing 2012 guidelines. We are living in an unprecedented era in nephrology with novel therapies, including sodium-glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists and non-steroidal mineralocorticoid receptor antagonists now being proven in multiple randomised controlled clinical trials to reduce both the progression of CKD and cardiovascular morbidity and mortality. The KDIGO 2024 CKD guideline is aimed at a broad audience looking after children and adults with CKD and provide practical and actionable steps to improve care. This commentary reviews the guideline sections pertaining to the evaluation and risk assessment of individuals with CKD from a European perspective. We feel that despite the last guideline being published 12 years ago, and that the assessment of CKD has been emphasized by many other national/international nephrology, cardiology and diabetology guidelines and societies, the diagnosis and treatment of CKD remains poor across Europe. As such the KDIGO 2024 CKD Guidelines should be seen as an urgent call to action to improve diagnosis and care of children and adults with CKD across Europe. We know what we need to do. We now need to get on and do it.

SGLT-2 inhibitors and nephrolithiasis risk: a meta-analysis.

BACKGROUND AND AIM: Sodium-glucose cotransporter (SGLT)-2 inhibitors are novel anti-diabetic medications with potential beneficial effects on cardiovascular and renal outcomes, metabolic parameters, and body weight. In addition to the beneficial effects on renal functions, including estimated glomerular filtration rate and reduction in proteinuria, recent studies have investigated the potential role of SGLT-2 inhibitor therapy on nephrolithiasis development. Nephrolithiasis, a condition affecting almost 10% of the general population at least once during a lifetime, is a common disorder with considerable risk for acute and chronic kidney injury and relatively few effective therapeutic options. MATERIALS AND METHODS: We have performed a literature search through multiple databases, including PubMed, Ovid/Medline, Web of Science, Scopus, and Cochrane Library. We have followed the systematic review and meta-analysis guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses.We have included a total of 11 635 698 patients who experienced nephrolithiasis from six clinical trials to conduct this meta-analysis study. In the pooled analysis, nephrolithiasis occurred in 1,27% of patients from the SGLT2i group (n = 739 197), compared to 1,56% of patients (n = 10 896 501) from the control arm (active control, placebo or no therapy). RESULTS: We have included a total of 11 635 698 participants who experienced nephrolithiasis from a total of six clinical studies with nephrolithiasis rates of 1,27% in the SGLT2i group (n = 739 197), compared to 1,56% in the control arm (n = 10 896 501). SGLT-2 inhibitor therapy has been associated with a lower risk for nephrolithiasis compared to placebo (OR 0.61, 95% CI, 0.53-0.70, p < 0.00001) or active therapy such as glucagon-like peptide 1 and dipeptidyl peptidase-IV inhibitors (OR 0.66, 95% CI, 0.47-0.93, p = 0.02). CONCLUSION: We have demonstrated a lower risk of nephrolithiasis risk with SGLT-2 inhibitor therapy compared to placebo or active control. Potential underlying mechanisms include osmotic diuresis leading to a reduction in the concentration of lithogenic substances, anti-inflammatory and anti-fibrotic effects, and an increase in urine pH. There is a clear need for future large-scale randomized clinical trials evaluating such associations for better understanding.

Prognostic Impact of Post-Transplant Diabetes Mellitus in Kidney allograft recipients: A Meta-analysis.

BACKGROUND AND AIM: Post-transplant diabetes mellitus (PTDM) is a complex condition arising from various factors including immunosuppressive medications, insulin resistance, impaired insulin secretion, and inflammatory processes. Its impact on patient and graft survival is a significant concern in kidney transplant recipients. PTDM's impact on kidney transplant recipients, including patient and graft survival and cardiovascular mortality, is a significant concern, given conflicting findings in previous studies. This meta-analysis was imperative to not only incorporate emerging evidence but also to delve into cause-specific mortality considerations. We aimed to comprehensively evaluate the association between PTDM and clinical outcomes, including all-cause and cardiovascular mortality, sepsis-related mortality, malignancy-related mortality, and graft loss, in kidney transplant recipients. MATERIALS AND METHODS: PubMed, Ovid/Medline, Web of Science, Scopus, and Cochrane Library databases were screened and studies evaluating the effect of PTDM on all-cause mortality, cardiovascular mortality, sepsis-related mortality, malignancy-related mortality, and overall graft loss in adult kidney transplant recipients were included. RESULTS: 53 studies, encompassing a total of 138,917 patients, to evaluate the association between PTDM and clinical outcomes were included. Our analysis revealed a significant increase in all-cause mortality (RR 1.70, 95% CI 1.53 to 1.89, P<0.001) and cardiovascular mortality (RR 1.86, 95% CI 1.36 to 2.54, P<0.001) among individuals with PTDM. Moreover, PTDM was associated with a higher risk of sepsis-related mortality (RR 1.96, 95% CI 1.51 to 2.54, P<0.001) but showed no significant association with malignancy-related mortality (RR 1.20, 95% CI 0.76 to 1.88). Additionally, PTDM was linked to an increased risk of overall graft failure (RR 1.33, 95% CI 1.16 to 1.54, P<0.001). CONCLUSION: These findings underscore the importance of comprehensive management strategies and the need for research targeting PTDM to improve outcomes in kidney transplant recipients.

Klotho in pregnancy and intrauterine development-potential clinical implications: a review from the European Renal Association CKD-MBD Working Group.

Intrauterine development is crucial for life-long health; therefore, elucidation of its key regulators is of interest for their potential prognostic and therapeutic implications. Originally described as a membrane-bound anti-aging protein, Klotho has evolved as a regulator of numerous functions in different organ systems. Circulating Klotho is generated by alternative splicing or active shedding from cell membranes. Recently, Klotho was identified as a regulator of placental function, and while Klotho does not cross the placental barrier, increased levels of circulating α-Klotho have been identified in umbilical cord blood compared with maternal blood, indicating that Klotho may also play a role in intrauterine development. In this narrative review, we discuss novel insights into the specific functions of the Klotho proteins in the placenta and in intrauterine development, while summarizing up-to-date knowledge about their structures and functions. Klotho plays a role in stem cell functioning, organogenesis and haematopoiesis. Low circulating maternal and foetal levels of Klotho are associated with preeclampsia, intrauterine growth restriction, and an increased perinatal risk for newborns, indicating a potential use of Klotho as biomarker and therapeutic target. Experimental administration of Klotho protein indicates a neuro- and nephroprotective potential, suggesting a possible future role of Klotho as a therapeutic agent. However, the use of Klotho as intervention during pregnancy is as yet unproven. Here, we summarize novel evidence, suggesting Klotho as a key regulator for healthy pregnancies and intrauterine development with promising potential for clinical use.

An update review of post-transplant diabetes mellitus: Concept, risk factors, clinical implications and management.

OBJECTIVE: Kidney transplantation is the gold standard therapeutic alternative for patients with end-stage renal disease; nevertheless, it is not without potential complications leading to considerable morbidity and mortality such as post-transplant diabetes mellitus (PTDM). This narrative review aims to comprehensively evaluate PTDM in terms of its diagnostic approach, underlying pathophysiological pathways, epidemiological data, and management strategies. METHODS: Articles were retrieved from electronic databases using predefined search terms. Inclusion criteria encompassed studies investigating PTDM diagnosis, pathophysiology, epidemiology, and management strategies. RESULTS: PTDM emerges as a significant complication following kidney transplantation, influenced by various pathophysiological factors including peripheral insulin resistance, immunosuppressive medications, infections, and proinflammatory pathways. Despite discrepancies in prevalence estimates, PTDM poses substantial challenges to transplant. Diagnostic approaches, including traditional criteria such as fasting plasma glucose (FPG) and HbA1c, are limited in their ability to capture early PTDM manifestations. Oral glucose tolerance test (OGTT) emerges as a valuable tool, particularly in the early post-transplant period. Management strategies for PTDM remain unclear, within sufficient evidence from large-scale randomized clinical trials to guide optimal interventions. Nevertheless, glucose-lowering agents and life style modifications constitute primary modalities for managing hyperglycemia in transplant recipients. DISCUSSION: The complex interplay between PTDM and the transplant process necessitates individualized diagnostic and management approaches. While early recognition and intervention are paramount, modifications to maintenance immunosuppressive regimens based solely on PTDM risk are not warranted, given the potential adverse consequences such as increased rejection risk. Further research is essential to refine management strategies and enhance outcomes for transplant recipients.

The role of anticomplement therapy in the management of the kidney allograft.

As the number of patients living with kidney failure grows, the need also grows for kidney transplantation, the gold standard kidney replacement therapy that provides a survival advantage. This may result in an increased rate of transplantation from HLA-mismatched donors that increases the rate of antibody-mediated rejection (AMR), which already is the leading cause of allograft failure. Plasmapheresis, intravenous immunoglobulin therapy, anti-CD20 therapies (i.e., rituximab), bortezomib and splenectomy have been used over the years to treat AMR as well as to prevent AMR in high-risk sensitized kidney transplant recipients. Eculizumab and ravulizumab are monoclonal antibodies targeting the C5 protein of the complement pathway and part of the expanding field of anticomplement therapies, which is not limited to kidney transplant recipients, and also includes complement-mediated microangiopathic hemolytic anemia, paroxysmal nocturnal hemoglobinuria, and ANCA-vasculitis. In this narrative review, we summarize the current knowledge concerning the pathophysiological background and use of anti-C5 strategies (eculizumab and ravulizumab) and C1-esterase inhibitor in AMR, either to prevent AMR in high-risk desensitized patients or to treat AMR as first-line or rescue therapy and also to treat de novo thrombotic microangiopathy in kidney transplant recipients.

Pancreatic steatosis is an independent risk factor for post-transplant diabetes mellitus in kidney transplant patients.

BACKGROUND AND AIM: Post-transplant diabetes mellitus (PTDM) is associated with an increased risk of post-transplant cardiovascular diseases, and several risk factors of PTDM have been shown in the literature. Yet, the relationship between hepatic and pancreatic steatosis with post-transplant diabetes mellitus remains vague. We aimed to evaluate pancreatic steatosis, a novel component of metabolic syndrome, and hepatic steatosis association with post-transplant diabetes mellitus in a single-center retrospective cohort study conducted on kidney transplant recipients. METHOD: We have performed a single-center retrospective cohort study involving all kidney transplant recipients. We have utilized pretransplant Fibrosis-4, nonalcoholic fatty liver disease fibrosis score, and abdominal computed tomography for the assessment of visceral steatosis status. RESULTS: We have included 373 kidney transplant recipients with a mean follow-up period of 32 months in our final analysis. Post-transplant diabetes mellitus risk is associated with older age (p < .001), higher body-mass index (p < .001), nonalcoholic fatty liver disease-fibrosis score (p = .002), hepatic (p < .001) or pancreatic (p < .001) steatosis on imaging and higher pre-transplant serum triglyceride (p = .003) and glucose levels (p = .001) after multivariate analysis. CONCLUSION: Our study illustrates that recipients' pancreatic steatosis is an independent predictive factor for post-transplant diabetes mellitus including in kidney transplant patients.

A potential approach toward the management of sepsis: The extracorporeal cytokine hemadsorption therapy.

Infectious diseases are among the most common cause of morbidity and mortality among hospitalized patients while systemic inflammatory response syndrome is primarily attributed to the imbalance between pro-inflammatory and anti-inflammatory cytokines. Despite the improvements in the antibiotherapy alternatives and diagnostic modalities, the morbidity and mortality rates of sepsis and septic shock are relatively high among patients admitted to the intensive care units. Extracorporeal cytokine hemadsorption therapies are therapeutic approaches for such patient group with promising early results that especially have grown during COVID-19 pandemic. In this narrative review, our aim is to evaluate the current pre-clinical and clinical knowledge regarding the use of cytokine filtration systems among patients with septic shock.

Angiopoietin as a Novel Prognostic Marker in Kidney Disease.

INTRODUCTION: Renal injury is among the leading causes of morbidity and mortality; however, there are no reliable indicators for determining the likelihood of developing chronic kidney disease (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. METHODS: 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 CKD progression. RESULTS: This review therefore emphasizes the importance of angiopoietin-2 and proposes that it could be an important predictor of AKI in clinical settings. CONCLUSION: 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.

Effect of Bimagrumab on body composition: a systematic review and meta-analysis.

BACKGROUND: Sarcopenia, a condition marked by progressive muscle mass and function decline, presents significant challenges in aging populations and those with chronic illnesses. Current standard treatments such as dietary interventions and exercise programs are often unsustainable. There is increasing interest in pharmacological interventions like bimagrumab, a monoclonal antibody that promotes muscle hypertrophy by inhibiting muscle atrophy ligands. Bimagrumab has shown effectiveness in various conditions, including sarcopenia. AIM: The primary objective of this meta-analysis is to evaluate the impact of bimagrumab treatment on both physical performance and body composition among patients diagnosed with sarcopenia. MATERIALS AND METHODS: This meta-analysis follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We systematically searched PubMed, Ovid/Medline, Web of Science, and the Cochrane Library databases up to June 2024 using appropriate Medical Subject Headings (MeSH) terms and keywords related to bimagrumab and sarcopenia. Eligible studies were randomized controlled trials (RCTs) that assessed the effects of bimagrumab on physical performance (e.g., muscle strength, gait speed, six-minute walk distance) and body composition (e.g., muscle volume, fat-free body mass, fat body mass) in patients with sarcopenia. Data extraction was independently performed by two reviewers using a standardized form, with discrepancies resolved through discussion or consultation with a third reviewer. RESULTS: From an initial search yielding 46 records, we screened titles, abstracts, and full texts to include seven RCTs in our meta-analysis. Bimagrumab treatment significantly increased thigh muscle volume (mean difference [MD] 5.29%, 95% confidence interval [CI] 4.08% to 6.50%, P < 0.001; moderate heterogeneity χ2 = 6.41, I2 = 38%, P = 0.17) and fat-free body mass (MD 1.90 kg, 95% CI 1.57 kg to 2.23 kg, P < 0.001; moderate heterogeneity χ2 = 8.60, I2 = 30%, P = 0.20), while decreasing fat body mass compared to placebo (MD - 4.55 kg, 95% CI - 5.08 kg to - 4.01 kg, P < 0.001; substantial heterogeneity χ2 = 27.44, I2 = 89%, P < 0.001). However, no significant improvement was observed in muscle strength or physical performance measures such as gait speed and six-minute walk distance with bimagrumab treatment, except among participants with slower baseline walking speeds or distances. DISCUSSION AND CONCLUSION: This meta-analysis provides valuable insights into the effects of bimagrumab on sarcopenic patients, highlighting its significant improvements in body composition parameters but limited impact on functional outcomes. The observed heterogeneity in outcomes across studies underscores the need for cautious interpretation, considering variations in study populations, treatment durations, and outcome assessments. While bimagrumab shows promise as a safe pharmacological intervention for enhancing muscle mass and reducing fat mass in sarcopenia, its minimal effects on muscle strength and broader physical performance suggest potential limitations in translating body composition improvements into functional gains. Further research is needed to clarify its long-term efficacy, optimal dosing regimens, and potential benefits for specific subgroups of sarcopenic patients.

Fructose: A New Variable to Consider in SIADH and the Hyponatremia Associated With Long-Distance Running?

Fructose has recently been proposed to stimulate vasopressin secretion in humans. Fructose-induced vasopressin secretion is not only postulated to result from ingestion of fructose-containing drinks but may also occur from endogenous fructose production via activation of the polyol pathway. This raises the question of whether fructose might be involved in some cases of vasopressin-induced hyponatremia, especially in situations where the cause is not fully known such as in the syndrome of inappropriate secretion of diuretic hormone (SIADH) and exercise-associated hyponatremia, which has been observed in marathon runners. Here we discuss the new science of fructose and vasopressin, and how it may play a role in some of these conditions, as well as in the complications associated with rapid treatment (such as the osmotic demyelination syndrome). Studies to test the role of fructose could provide new pathophysiologic insights as well as novel potential treatment strategies for these common conditions.

Thyroid hormone Beta receptor agonists for treatment of kidney disease: A promising agent?

BACKGROUND: Chronic kidney disease is a common disorder affecting a significant portion of the adult population with high mortality and morbidity. Obesity and hyperlipidemia are prevalent in chronic kidney disease, and they may trigger fat accumulation in renal parenchyma and eventually fatty kidney. Chronic kidney disease and fatty kidney are also strongly associated with nonalcoholic fatty liver disease. Because they both lead to detrimental effects on organ function, they both need to be treated effectively to improve the outcome. AIM: In this narrative review, we have hypothesized that thyroid hormone beta receptor agonists, a novel drug group, may potentially be beneficial in the management of chronic kidney disease due to its promising outcomes among patients with nonalcoholic fatty liver disease, a condition sharing multiple common underlying pathophysiological mechanisms. RESULTS AND CONCLUSION: Thyroid hormone beta receptors are abundantly expressed in liver and kidney tissues, while both nonalcoholic fatty liver disease and chronic kidney disease share various similar pathophysiological mechanisms and triggers. Therefore, thyroid hormone beta receptor agonists may become a promising tool in the management of patients with chronic kidney disease.

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.

Social isolation and loneliness: Undervalued risk factors for disease states and mortality.

Social isolation and loneliness are two common but undervalued conditions associated with a poor quality of life, decreased overall health and mortality. In this review, we aim to discuss the health consequences of social isolation and loneliness. We first provide the potential causes of these two conditions. Then, we explain the pathophysiological processes underlying the effects of social isolation and loneliness in disease states. Afterwards, we explain the important associations between these conditions and different non-communicable diseases, as well as the impact of social isolation and loneliness on health-related behaviours. Finally, we discuss the current and novel potential management strategies for these conditions. Healthcare professionals who attend to socially isolated and/or lonely patients should be fully competent in these conditions and assess their patients thoroughly to detect and properly understand the effects of isolation and loneliness. Patients should be offered education and treatment alternatives through shared decision-making. Future studies are needed to understand the underlying mechanisms better and to improve the treatment strategies for both social isolation and loneliness.