Correlations between preoperative fluid status assessed by bioimpedance analysis and hypotension during anaesthesia induction.

INTRODUCTION: Hypovolaemia is presumed to be a common risk factor of postinduction hypotension (PIH), despite worldwide improvement in preoperative volume optimization. Correct assessment of fluid status in patients undergoing general anaesthesia remains a major challenge for anaesthesiologists. Bioimpedance analysis (BIA) is a sensitive method that allows objective assessment of patient fluid status as it can detect subclinical changes. The study's main purpose was to determine the correlation between the preoperative BIA assessed fluid status and PIH. MATERIAL AND METHODS: This was an observational single centre study that included patients undergoing elective surgery. We defined PIH as the blood pressure decrease occurring during the first 10 minutes after induction of anaesthesia and orotracheal intubation before surgical incision. We standardized BIA evaluation, patient pre anaesthetic and preoperative preparation, technique and monitoring of anaesthesia. RESULTS: Our study included 115 patients. The mean age of the population was 58.1 years and the median values for total and intracellular water were 35.1 L and 19.3 L, respectively. In the univariable and multivariable analysis, only total body and intracellular water were associated with different definitions of PIH. There was no correlation between any of the BIA-derived parameters of fluid status and the duration of PIH. CONCLUSIONS: Our study shows that in elective surgery, bioimpedance could detect subtle, subclinical fluid parameters that are associated with PIH.

Exploring Adiposity and Chronic Kidney Disease: Clinical Implications, Management Strategies, Prognostic Considerations.

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.

Ziltivekimab for anemia and atherosclerosis in chronic kidney disease: a new hope?

Anemia of chronic kidney disease is a multifactorial condition secondary to various etiologies, including nutritional deficiencies, chronic inflammation, erythropoietin deficiency or resistance, bone marrow suppression, iron deficiency and adverse drug effects. The major therapeutic intervention for anemia among chronic kidney disease patients is erythropoiesis-stimulating agents. However, a limitation of erythropoiesis-stimulating agents is the risk for thromboembolic events, hypertension, seizures, solid organ malignancies and hyporesponsiveness. A novel interleukin-6 monoclonal antibody, ziltivekimab, has been evaluated for managing anemia in chronic kidney disease patients in pilot clinical trials with promising outcomes, including an improvement in hemoglobin levels and reduction of inflammatory parameters. These trials have shown that ziltivekimab does not increase the risk for cytopenia or infectious complications as has been described for other interleukin-6-targeting monoclonal antibodies, like tocilizumab. Furthermore, potentially beneficial effects on serum lipid profile have been reported, leading to the hypothesis of a favorable impact of the drug on atherosclerotic complications. In addition, ziltivekimab has shown efficacy in improving anemia parameters, including hemoglobin levels and iron studies. Ziltivekimab deserves full scale clinical development, and to this aim, large-scale clinical trials are under way.

Prognostic value of lung ultrasonography and bioimpedance spectroscopy in patients with heart failure and reduced ejection fraction.

Introduction: Chronic heart failure (HF) represents a major global public health problem, and despite significant advances in diagnosis and management over the past two decades, HF patients still have a poor prognosis. The aim of the study was to evaluate the relationship between lung congestion, as assessed by lung ultrasonography (LUS), bioimpedance spectroscopy, body fluid compartments, and echocardiographic parameters, and to determine the effect of these associations on all-cause mortality in HF patients. Material and methods: Eligible patients with a left ventricular ejection fraction (LVEF) below 45% were identified via daily echocardiography assessments. Lung ultrasonography was performed with patients in the supine position, for a total of 28 sites per complete examination. The extracellular water (ECW) was determined using a BIS device. Results: Our study included 122 patients (67.2% males) with a mean age of 67.2 years. In the multivariable linear regression analysis, including all the univariable predictors of lung congestion, only New York Heart Association (NYHA) class, ECW, estimated glomerular filtration rate (eGFR), and LVEF levels maintained an independent association with the number of B-lines. During the follow-up, 33 patients died. In multivariable Cox analysis, a B-line number of at least 15 remained significantly associated with all-cause mortality, independently of age, sex, diabetes, LVEF, estimated glomerular filtration rate, C-reactive protein, N-terminal pro-brain natriuretic peptide, or ECW values (adjusted HR = 3.84, 95% CI: 1.12-13.09). Conclusions: We show for the first time in HF patients that pulmonary congestion, as assessed by LUS, is associated with the severity of NYHA class, LVEF, eGFR, and ECW, and it identifies those at increased risk of death.

Glucagon and glucagon-like peptide-1 dual agonist therapy: A possible future towards fatty kidney disease.

BACKGROUND: Obesity is a growing epidemic affecting approximately 40% of the adult population in developed countries with major health consequences and comorbidities, including diabetes mellitus and insulin resistance, metabolically associated fatty liver disease, atherosclerotic cardiovascular and cerebrovascular diseases and chronic kidney disease. Pharmacotherapies targeting significant weight reduction may have beneficial effects on such comorbidities, though such therapeutic options are highly limited. In this narrative review, we aim to evaluate current knowledge regarding dual agonist therapies and potential implications for managing fatty kidney and chronic kidney disease. RESULTS AND CONCLUSION: Glucagon-like peptide-1 agonists and sodium-glucose cotransporter-2 inhibitors are two novel classes of glucose-lowering medications with potential implications and beneficiary effects on renal outcomes, including estimated glomerular filtration rate, albuminuria and chronic kidney disease progression. Recently, dual agonist therapies targeting glucagon-like peptide-1 and glucagon receptors, namely survodutide and cotadutide, have been evaluated in managing metabolically associated fatty liver disease, a well-established example of visceral obesity. Fatty kidney is another novel concept implicated in the pathophysiology of chronic kidney disease among patients with visceral obesity.

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.

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.

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.

The association between klotho and kidney and cardiovascular outcomes: a comprehensive systematic review and meta-analysis.

Background: Chronic kidney disease (CKD) and end-stage renal disease (ESKD) are significant global health challenges associated with progressive kidney dysfunction and numerous complications, including cardiovascular disease and mortality. This study aims to explore the potential association between plasma klotho levels and various prognostic outcomes in CKD and ESKD, including all-cause mortality, cardiovascular events, metabolic syndrome development and adverse renal events necessitating renal replacement therapies. Methods: A literature search was conducted through 3 June 2024 using the electronic databases Cochrane Library, Ovid MEDLINE, CINAHL, Web of Science, SCOPUS and PubMed. This systematic review adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results: Fourteen studies were included. For all-cause mortality, comparing CKD patients with low versus high klotho levels showed a significant association {odds ratio [OR] 1.81 [95% confidence interval (CI) 1.34-2.44], P = .0001}, with substantial heterogeneity (I 2 = 69%). Excluding one study reduced heterogeneity (I 2 = 43%) while maintaining significance [OR 1.97 (95% CI 1.45-2.66), P < .0001]. Cardiovascular mortality was higher in patients with low klotho levels [OR 2.11 (95% CI 1.61-2.76), P < .00001], with low heterogeneity (I 2 = 25%). Excluding one study eliminated heterogeneity (I 2 = 0%) while maintaining significance [OR 2.39 (95% CI 1.83-3.12), P < .00001]. Composite cardiovascular events did not differ significantly between low and high klotho groups [OR 1.51 (95% CI 0.82-2.77), P = .18], but with high heterogeneity (I 2 = 72%). Patients with low klotho levels had a higher risk of adverse renal events [OR 2.36 (95% CI 1.37-4.08), P = .002], with moderate heterogeneity (I 2 = 61%). Sensitivity analysis reduced heterogeneity (I 2 = 0%) while maintaining significance [OR 3.08 (95% CI 1.96-4.85), P < .00001]. Specifically, for ESKD or kidney replacement therapy risk, low klotho levels were associated with an increased risk [OR 2.30 (95% CI 1.26-4.21), P = .007]. Similarly, CKD progression risk was higher in patients with lower klotho levels [OR 2.48 (95% CI 1.45-4.23), P = .0009]. Conclusion: Lower serum klotho levels serve as a significant predictor of adverse outcomes, including increased risks of all-cause mortality, cardiovascular mortality and progression to end-stage kidney disease among CKD patients.

Cognitive impairment in patients on dialysis: can we prevent it?

Chronic kidney disease (CKD) is among the leading causes of morbidity and mortality as it affects more than 10% of the global adult population. Cognitive impairment has a positive correlation with the stage of CKD. It has been recorded in more than half of CKD patients undergoing kidney replacement therapy. The assessment of cognitive function in dialysis patients presents challenges due to various patient limitations. Such a common debilitating comorbidity of CKD has no approved treatment option, highlighting the importance of preventive measures and screening modalities. Erythropoietin therapy, exercise training, cognitive stimulation or behavioral therapies, alterations in dialysis frequency, dialysate cooling and kidney transplantation have been proposed as potential preventive and/or therapeutic options with variable efficiency at a clinical level. Regular screening, such as yearly, for cognitive impairment in maintenance dialysis patients is not only beneficial for timely and accurate diagnosis but also crucial for effective management and improved patient care. However, current practices face challenges, including the absence of validated tools specific for kidney failure and complications arising from patient conditions.

The Impact of Frailty and Severe Cognitive Impairment on Survival Time and Time to Initiate Dialysis in Older Adults With Advanced Chronic Kidney Disease: A Prospective Observational Cohort Study.

Background and objectives Frailty and cognitive impairment significantly impact survival time and time to initiate dialysis in older adults with advanced chronic kidney disease (CKD). This study aims to evaluate the effects of frailty and cognitive impairment on these outcomes and determine the most effective assessment tool for predicting early dialysis initiation and short survival time. Materials and methods This prospective observational cohort study involved 240 patients aged ≥65 years with stage 4 or 5 CKD, recruited from a nephrology outpatient department (ambulatory care) between March 2020 and March 2021. Frailty was assessed using the Physical Frailty Phenotype (PFP), PRISMA-7, Clinical Frailty Scale (CFS), and FRAIL scale. Cognitive function was evaluated using the Montreal Cognitive Assessment (MoCA). The primary outcomes were time to initiate dialysis and survival time, with secondary outcomes including hospitalization rates, length of stay, and mortality after dialysis initiation. Results Frail patients only showed significantly shorter time to dialysis initiation when identified by the PFP and FRAIL scale (28.3 months for frail vs. 31.2 months for non-frail, p = 0.028; 26.9 months for frail vs. 30.9 months for non-frail, p = 0.038). The PFP, FRAIL, and CFS tools indicated significantly shorter survival times for frail patients compared to non-frail patients (26.8 months for frail vs. 30.6 months for non-frail, p = 0.003). Frailty is strongly correlated with severe cognitive impairment, as 45.5% of frail patients (according to the FRAIL scale) have dementia compared to 15.1% of non-frail patients (p<0.001). However, cognitive impairment did not significantly affect the time to dialysis initiation or survival time. Hospitalization rates and length of stay in the hospital were significantly higher only for frail patients identified by PRISMA-7, with a median hospital length of stay of 9.15 days for frail patients vs 6.37 days for non-frail patients (p = 0.044). Overall, 37.5% of the patients did not survive during the study follow-up, with frail patients having a higher mortality rate. Conclusion Frailty, mainly when assessed by PFP and FRAIL, is a significant predictor of early dialysis initiation and reduced survival time in older adults with advanced CKD. Cognitive impairment, while prevalent, did not independently predict these outcomes. Regular frailty screening should be incorporated into CKD management to tailor interventions and improve patient outcomes.

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.

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.

Understanding the Role of Sex Hormones in Cardiovascular Kidney Metabolic Syndrome: Toward Personalized Therapeutic Approaches.

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.

Proximal tubule hypertrophy and hyperfunction: a novel pathophysiological feature in disease states.

The role of proximal tubules (PTs), a major component of the renal tubular structure in the renal cortex, has been examined extensively. Along with its physiological role in the reabsorption of various molecules, including electrolytes, amino acids and monosaccharides, transcellular transport of different hormones and regulation of homeostasis, pathological events affecting PTs may underlie multiple disease states. PT hypertrophy or a hyperfunctioning state, despite being a compensatory mechanism at first in response to various stimuli or alterations at tubular transport proteins, have been shown to be critical pathophysiological events leading to multiple disorders, including diabetes mellitus, obesity, metabolic syndrome and congestive heart failure. Moreover, pharmacotherapeutic agents have primarily targeted PTs, including sodium-glucose cotransporter 2, urate transporters and carbonic anhydrase enzymes. In this narrative review, we focus on the physiological role of PTs in healthy states and the current understanding of the PT pathologies leading to disease states and potential therapeutic targets.

Metabolically healthy obesity and chronic kidney disease risk: exploring the dynamics.

Obesity represents a prevalent global health concern with significant implications for various diseases, including chronic kidney disease (CKD). Within this landscape, the phenomenon of metabolically healthy obesity has emerged, challenging traditional notions about the health risks associated with excess weight. While traditional CKD risk factors involve obesity, metabolic syndrome, diabetes, and hypertension, the metabolically healthy obese (MHO) subgroup disrupts these assumptions. Our main objective in this study is to integrate existing literature on CKD in MHO individuals. In this endeavor, we delve into the pathophysiological foundations, the transition between obesity phenotypes and their impact on renal health, examine the implications of their metabolic resilience on mortality within a renal context, and explore potential management strategies specifically designed for MHO individuals. Offering a comprehensive overview of the pathophysiology, we cover various factors contributing to the risk of CKD in the metabolically healthy obese setting, including inflammation, cytokines, hemodynamics, and the renin-angiotensin-aldosterone system, gastrointestinal microbiota, diet, exercise, adipose distribution, and lipotoxicity. Through this synthesis, we aim to provide a comprehensive understanding of the risk of CKD in those classified as MHO.

Exploring the nexus: The place of kidney diseases within the cardiovascular-kidney-metabolic syndrome spectrum.

Cardiovascular-kidney-metabolic (CKM) syndrome and chronic kidney disease (CKD) are two significant comorbidities affecting a large proportion of the general population with considerable crosstalk. In addition to substantial co-incidence of CKD and CKM syndrome in epidemiological studies, clinical and pre-clinical studies have identified similar pathophysiological pathways leading to both entities. Patients with CKM syndrome are more prone to develop acute kidney injury and CKD, while therapeutic alternatives and their success rates are considerably lower in such patient groups. Nevertheless, the association between CKM syndrome and CKD or ESKD is bidirectional rather than being a cause-effect relationship as patients with CKD are also prone to develop peripheral insulin resistance, high blood pressure, and dyslipidemia. Furthermore, such patients are less likely to receive kidney transplantation in addition to the higher allograft dysfunction risk. We hereby aim to evaluate the association in-between kidney diseases and CKM syndrome, including epidemiological data, pre-clinical studies with pathophysiological pathways, and potential therapeutic perspectives.

Candidate protein biomarkers in chronic kidney disease: a proteomics study.

Proteinuria poses a substantial risk for the progression of chronic kidney disease (CKD) and its related complications. Kidneys excrete hundreds of individual proteins, some with a potential impact on CKD progression or as a marker of the disease. However, the available data on specific urinary proteins and their relationship with CKD severity remain limited. Therefore, we aimed to investigate the urinary proteome and its association with kidney function in CKD patients and healthy controls. The proteomic analysis of urine samples showed CKD stage-specific differences in the number of detected proteins and the exponentially modified protein abundance index for total protein (p = 0.007). Notably, specific urinary proteins such as B2MG, FETUA, VTDB, and AMBP exhibited robust negative associations with kidney function in CKD patients compared to controls. Also, A1AG2, CD44, CD59, CERU, KNG1, LV39, OSTP, RNAS1, SH3L3, and UROM proteins showed positive associations with kidney function in the entire cohort, while LV39, A1BG, and CERU consistently displayed positive associations in patients compared to controls. This study suggests that specific urinary proteins, which were found to be negatively or positively associated with the kidney function of CKD patients, can serve as markers of dysfunctional or functional kidneys, respectively.

A study on the early metabolic effects of salt and fructose consumption: the protective role of water.

Increasing serum osmolality has recently been linked with acute stress responses, which over time can lead to increased risk for obesity, hypertension, and other chronic diseases. Salt and fructose are two major stimuli that can induce acute changes in serum osmolality. Here we investigate the early metabolic effects of sodium and fructose consumption and determine whether the effects of sodium or fructose loading can be mitigated by blocking the change in osmolality with hydration. Forty-four healthy subjects without disease and medication were recruited into four groups. After overnight fasting, subjects in Group 1 drank 500 mL of salty soup, while those in Group 2 drank 500 mL of soup without salt for 15 min. Subjects in Group 3 drank 500 mL of 100% apple juice in 5 min, while subjects in Group 4 drank 500 mL of 100% apple juice and 500 mL of water in 5 min. Blood pressure (BP), plasma sodium, and glucose levels were measured every 15 min in the first 2 h. Serum and urine osmolarity, serum uric acid, cortisol, fibroblast growth factor 21 (FGF21), aldosterone, adrenocorticotropic hormone (ACTH) level, and plasma renin activity (PRA) were measured at the baseline and 2 h. Both acute intake of salt or fructose increased serum osmolality (maximum ∼4 mOsm/L peaking at 75 min) associated with a rise in systolic and diastolic BP, PRA, aldosterone, ACTH, cortisol, plasma glucose, uric acid, and FGF21. Salt tended to cause greater activation of the renin-angiotensin-system (RAS), while fructose caused a greater rise in glucose and FGF21. In both cases, hydration could prevent the osmolality and largely block the acute stress response. Acute changes in serum osmolality can induce remarkable activation of the ACTH-cortisol, RAS, glucose metabolism, and uric acid axis that is responsive to hydration. In addition to classic dehydration, salt, and fructose-containing sugars can activate these responses. Staying well hydrated may provide benefits despite exposure to sugar and salt. More studies are needed to investigate whether hydration can block the chronic effects of sugar and salt on disease.

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.