Glomerular and tubular effects of dapagliflozin, eplerenone and their combination in patients with chronic kidney disease: A post-hoc analysis of the ROTATE-3 study.

AIM: Sodium-glucose co-transporter 2 inhibitors and mineralocorticoid receptor antagonists reduce albuminuria and the risk of kidney failure. The aim of this study was to investigate the effects of both agents alone and in combination on markers of the glomerular endothelial glycocalyx and tubular function. METHODS: This post-hoc analysis utilized data of the ROTATE-3 study, a randomized cross-over study in 46 adults with chronic kidney disease and urinary albumin excretion ≥100 mg/24 h, who were treated for 4 weeks with dapagliflozin, eplerenone or its combination. The effects of dapagliflozin, eplerenone and the combination on outcome measures such as heparan sulphate, neuro-hormonal markers and tubular sodium handling were assessed with mixed repeated measures models. RESULTS: The mean percentage change from baseline in heparan sulphate after 4 weeks treatment with dapagliflozin, eplerenone or dapagliflozin-eplerenone was -34.8% (95% CI -52.2, -10.9), -5.9% (95% CI -32.5, 31.3) and -28.1% (95% CI -48.4, 0.1) respectively. The mean percentage change from baseline in plasma aldosterone was larger with eplerenone [38.9% (95% CI 2.8, 87.7)] and dapagliflozin-eplerenone [32.2% (95% CI -1.5, 77.4)], compared with dapagliflozin [-12.5% (95% CI -35.0, 17.8)], respectively. Mean percentage change from baseline in copeptin with dapagliflozin, eplerenone or dapagliflozin-eplerenone was 28.4% (95% CI 10.7, 49.0), 4.2% (95% CI -10.6, 21.4) and 23.8% (95% CI 6.6, 43.9) respectively. Dapagliflozin decreased proximal absolute sodium reabsorption rate by 455.9 mmol/min (95% CI -879.2, -32.6), while eplerenone decreased distal absolute sodium reabsorption rate by 523.1 mmol/min (95% CI -926.1, -120.0). Dapagliflozin-eplerenone decreased proximal absolute sodium reabsorption [-971.0 mmol/min (95% CI -1411.0, -531.0)], but did not affect distal absolute sodium reabsorption [-9.2 mmol/min (95% CI -402.0, 383.6)]. CONCLUSIONS: Dapagliflozin and eplerenone exert different effects on markers of glomerular and tubular function supporting the hypothesis that different mechanistic pathways may account for their kidney protective effects.

Albuminuria-Lowering Effect of Dapagliflozin, Eplerenone, and Their Combination in Patients with Chronic Kidney Disease: A Randomized Crossover Clinical Trial.

BACKGROUND: Sodium glucose cotransporter 2 (SGLT2) inhibitors and mineralocorticoid receptor antagonists (MRAs) reduce the urinary albumin-to-creatinine ratio (UACR) and confer kidney and cardiovascular protection in patients with CKD. We assessed efficacy and safety of the SGLT2 inhibitor dapagliflozin and MRA eplerenone alone and in combination in patients with CKD. METHODS: We conducted a randomized open-label crossover trial in patients with urinary albumin excretion ≥100 mg/24 hr, eGFR 30-90 ml/min per 1.73 m2, who had been receiving maximum tolerated stable doses of an ACE inhibitor (ACEi) or angiotensin receptor blocker (ARB). Patients were assigned to 4-week treatment periods with dapagliflozin 10 mg/day, eplerenone 50 mg/day, or their combination in random order, separated by 4-week washout periods. Primary outcome was the correlation in UACR changes between treatments. Secondary outcome was the percent change in 24-hour UACR from baseline. RESULTS: Of 57 patients screened, 46 were randomly assigned (mean eGFR, 58.1 ml/min per 1.73 m2; median UACR, 401 mg/g) to the three groups. Mean percentage change from baseline in UACR after 4 weeks of treatment with dapagliflozin, eplerenone, and dapagliflozin-eplerenone was -19.6% (95% confidence interval [CI], -34.3 to -1.5), -33.7% (95% CI, -46.1 to -18.5), and -53% (95% CI, -61.7 to -42.4; P<0.001 versus dapagliflozin; P=0.01 versus eplerenone). UACR change during dapagliflozin or eplerenone treatment did not correlate with UACR change during dapagliflozin-eplerenone (r=-0.13; P=0.47; r=-0.08; P=0.66, respectively). Hyperkalemia was more frequently reported with eplerenone (n=8; 17.4%) compared with dapagliflozin (n=0; 0%) or dapagliflozin-eplerenone (n=2; 4.3%; P between-groups=0.003). CONCLUSIONS: Albuminuria changes in response to dapagliflozin and eplerenone did not correlate, supporting systematic rotation of these therapies to optimize treatment. Combining dapagliflozin with eplerenone resulted in a robust additive UACR-lowering effect. A larger trial in this population is required to confirm long-term efficacy and safety of combined SGLT2 inhibitor and MRA treatment. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: European Union Clinical Trials Register, EU 2017-004641-25.

The Role of Specialized Pro-Resolving Lipid Mediators in Inflammation-Induced Carcinogenesis.

Cancer is a process involving cell mutation, increased proliferation, invasion, and metastasis. Over the years, this condition has represented one of the most concerning health problems worldwide due to its significant morbidity and mortality. At present, the incidence of cancer continues to grow exponentially. Thus, it is imperative to open new avenues in cancer research to understand the molecular changes driving DNA transformation, cell-to-cell interaction derangements, and immune system surveillance decay. In this regard, evidence supports the relationship between chronic inflammation and cancer. In light of this, a group of bioactive lipids derived from polyunsaturated fatty acids (PUFAs) may have a position as novel anti-inflammatory molecules known as the specialized pro-resolving mediators (SPMs), a group of pro-resolutive inflammation agents that could improve the anti-tumor immunity. These molecules have the potential role of chemopreventive and therapeutic agents for various cancer types, and their effects have been documented in the scientific literature. Thus, this review objective centers around understanding the effect of SPMs on carcinogenesis and their potential therapeutic effect.

Long-term mortality and trajectory of potassium measurements following an episode of acute severe hyperkalaemia.

BACKGROUND: Hyperkalaemia is a common condition in patients with comorbidities such as chronic kidney disease (CKD) or congestive heart failure (HF). Moreover, severe hyperkalaemia is a potentially life-threatening condition that is associated with a higher risk of adverse clinical events such as ventricular arrhythmias and sudden cardiac death. Currently, data regarding the prognostic implications of chronic hyperkalaemia are available; however, information about the long-term clinical consequences after an episode of severe hyperkalaemia remains scarce. The objective of this study was to evaluate the association between the trajectory of potassium measurements in patients with acute hyperkalaemia and long-term all-cause mortality. METHODS: This is a retrospective observational study that included patients with acute severe hyperkalaemia [potassium (K) >6 mEq/L] without haemolysis in the emergency room of Dr Peset University Hospital in Valencia, Spain searching the lab database from January 2016 to March 2017. The multivariable-adjusted association of serum potassium with mortality was assessed by using comprehensive state-of-the-art regression methods that can accommodate time-dependent exposure modelling. RESULTS: We found 172 episodes of acute hyperkalaemia in 160 patients in the emergency room. The mean ± standard deviation age of the sample was 77 ± 12 years and 60.5% were males. The most frequent comorbidities were CKD (71.2%), HF (35%) and diabetes mellitus (56.9%). Only 11.9% of the patients were on chronic dialysis. A quarter of the patients did not have previous CKD, making hyperkalaemia an unpredictable life-threatening complication. During the acute episode, mean potassium and estimated glomerular filtration rate (eGFR) were 6.6 ± 0.6 (range 6.1-9.2) mEq/L and 23 ± 16 (range 2-84) mL/min/1.73 m2, respectively. After a median (interquartile range) follow-up of 17.3 (2.2-23.7) months, 68 patients died (42.5%). Recurrences of hyperkalaemia (K >5.5 mEq/L) were detected in 39.5% of the patients who were monitored during follow-up. We found that previous potassium levels during an acute severe hyperkalaemia episode were not predictors of mortality. Conversely, the post-discharge longitudinal trajectories of potassium were able to predict all-cause mortality (overall P = 0.0015). The effect of transitioning from hyperkalaemia to normokalaemia (K >5.5 mEq/L to K ≤5.5 mEq/L) after the acute episode was significant, and inversely associated with the risk of mortality. CONCLUSIONS: Potassium levels prior to a severe hyperkalaemic event do not predict mortality. Conversely, following an episode of acute severe hyperkalaemia, serial kinetics of potassium trajectories predict the risk of death. Further evidence is needed to confirm these findings and clarify the optimal long-term management of these patients.

Role of Omega-3 Fatty Acids as Non-Photic Zeitgebers and Circadian Clock Synchronizers.

Omega-3 fatty acids (ω-3 FAs) are well-known for their actions on immune/inflammatory and neurological pathways, functions that are also under circadian clock regulation. The daily photoperiod represents the primary circadian synchronizer ('zeitgeber'), although diverse studies have pointed towards an influence of dietary FAs on the biological clock. A comprehensive literature review was conducted following predefined selection criteria with the aim of updating the evidence on the molecular mechanisms behind circadian rhythm regulation by ω-3 FAs. We collected preclinical and clinical studies, systematic reviews, and metanalyses focused on the effect of ω-3 FAs on circadian rhythms. Twenty animal (conducted on rodents and piglets) and human trials and one observational study providing evidence on the regulation of neurological, inflammatory/immune, metabolic, reproductive, cardiovascular, and biochemical processes by ω-3 FAs via clock genes were discussed. The evidence suggests that ω-3 FAs may serve as non-photic zeitgebers and prove therapeutically beneficial for circadian disruption-related pathologies. Future work should focus on the role of clock genes as a target for the therapeutic use of ω-3 FAs in inflammatory and neurological disorders, as well as on the bidirectional association between the molecular clock and ω-3 FAs.

Cardiovascular risk factors and the impact on prognosis in patients with chronic kidney disease secondary to autosomal dominant polycystic kidney disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent hereditary renal disease. There is an increased rate of cardiovascular disease (CVD) in ADPKD. In this study, we evaluate the prevalence of cardiovascular risk factors, the achievement rates for treatment goals and cardiovascular events (CVE) in ADPKD and their relations with asymptomatic CVD in CKD from other etiologies (CKDoe) and controls. METHODS: We evaluated 2445 CKD patients (2010-2012). The information collected was: clinical, anthropometric and analytical parameters, treatments and CVD evaluation (intima-media thickness (IMT), atheromatous plaque presence and ankle-brachial index (ABI)). Laboratory, vital status, CVE and hospitalizations were collected for 4 years. RESULTS: ADPKD patients had a worse renal function and worst achievement of blood pressure, higher parathormone levels but lower proteinuria compared to CKDoe. ADPKD patients presented lower IMT values than other groups, however, an intermediate rate of pathologic ABI and atheromatous plaque was present. More than half of the patients received statins, achieving LDL-c levels < 100 only in 50 and 39.8% of them (ADPKD and CKDoe respectively). The number of CVE during the follow-up period was low. In adjusted Cox regression model, ADPDK had the lowest occurrence of CVE of all three groups (HR:0.422, 95%CI 0.221-0.808, p = 0.009). CONCLUSION: ADPKD patients show intermediate control rates of CVD. A better control of CVD risk seems to be related with a lower load of CVD compared to other groups, which may lead in the long term to a better prognosis. Further investigation is necessary to determine cardiovascular prognosis in ADPKD.

The Role of the α Cell in the Pathogenesis of Diabetes: A World beyond the Mirror.

Type 2 Diabetes Mellitus (T2DM) is one of the most prevalent chronic metabolic disorders, and insulin has been placed at the epicentre of its pathophysiological basis. However, the involvement of impaired alpha (α) cell function has been recognized as playing an essential role in several diseases, since hyperglucagonemia has been evidenced in both Type 1 and T2DM. This phenomenon has been attributed to intra-islet defects, like modifications in pancreatic α cell mass or dysfunction in glucagon's secretion. Emerging evidence has shown that chronic hyperglycaemia provokes changes in the Langerhans' islets cytoarchitecture, including α cell hyperplasia, pancreatic beta (ß) cell dedifferentiation into glucagon-positive producing cells, and loss of paracrine and endocrine regulation due to ß cell mass loss. Other abnormalities like α cell insulin resistance, sensor machinery dysfunction, or paradoxical ATP-sensitive potassium channels (KATP) opening have also been linked to glucagon hypersecretion. Recent clinical trials in phases 1 or 2 have shown new molecules with glucagon-antagonist properties with considerable effectiveness and acceptable safety profiles. Glucagon-like peptide-1 (GLP-1) agonists and Dipeptidyl Peptidase-4 inhibitors (DPP-4 inhibitors) have been shown to decrease glucagon secretion in T2DM, and their possible therapeutic role in T1DM means they are attractive as an insulin-adjuvant therapy.

Valvular heart disease and calcification in CKD: more common than appreciated.

Ischaemic heart disease, sudden cardiac death and arrhythmias, heart failure, stroke and peripheral arterial disease make up >50% of the causes of death in advanced chronic kidney disease (CKD). Calcification of the vascular tree and heart valves is partially related to these complications and has received growing attention in the literature. However, the main focus of research has been on the pathophysiology and consequences of vascular calcification, with less attention being paid to valvular calcification (VC) and its impact on the survival of CKD patients. Although VC has long been seen as an age-related degenerative disorder with minimal functional impact, several studies proved that it carries an increased risk of death and clinical consequences different from those of vascular calcification. In dialysis patients, the annual incidence of aortic valve calcification is nearly 3.3% and the reported prevalence of aortic and mitral VC varies between 25% and 59%. Moreover, calcification of both valves occurs 10-20 years earlier in CKD patients compared with the general population. Therefore, the purpose of this review is to summarize the current knowledge on the pathophysiology and relevance of VC in CKD patients, and to highlight specific clinical consequences and potential therapeutic implications.

Epicardial Adipose Tissue, Adiponectin and Leptin: A Potential Source of Cardiovascular Risk in Chronic Kidney Disease.

The importance of cardiometabolic factors in the inception and progression of atherosclerotic cardiovascular disease is increasingly being recognized. Beyond diabetes mellitus and metabolic syndrome, other factors may be responsible in patients with chronic kidney disease (CKD) for the high prevalence of cardiovascular disease, which is estimated to be 5- to 20-fold higher than in the general population. Although undefined uremic toxins are often blamed for part of the increased risk, visceral adipose tissue, and in particular epicardial adipose tissue (EAT), have been the focus of intense research in the past two decades. In fact, several lines of evidence suggest their involvement in atherosclerosis development and its complications. EAT may promote atherosclerosis through paracrine and endocrine pathways exerted via the secretion of adipocytokines such as adiponectin and leptin. In this article we review the current knowledge of the impact of EAT on cardiovascular outcomes in the general population and in patients with CKD. Special reference will be made to adiponectin and leptin as possible mediators of the increased cardiovascular risk linked with EAT.

Sex differences in mental stress-induced myocardial ischemia in young survivors of an acute myocardial infarction.

OBJECTIVES: Emotional stress may disproportionally affect young women with ischemic heart disease. We sought to examine whether mental stress-induced myocardial ischemia (MSIMI), but not exercise-induced ischemia, is more common in young women with previous myocardial infarction (MI) than in men. METHODS: We studied 98 post-MI patients (49 women and 49 men) aged 38 to 60 years. Women and men were matched for age, MI type, and months since MI. Patients underwent technetium-99m sestamibi perfusion imaging at rest, after mental stress, and after exercise/pharmacological stress. Perfusion defect scores were obtained with observer-independent software. A summed difference score (SDS), the difference between stress and rest scores, was used to quantify ischemia under both stress conditions. RESULTS: Women 50 years or younger, but not older women, showed a more adverse psychosocial profile than did age-matched men but did not differ for conventional risk factors and tended to have less angiographic coronary artery disease. Compared with age-matched men, women 50 years or younger exhibited a higher SDS with mental stress (3.1 versus 1.5, p = .029) and had twice the rate of MSIMI (SDS ≥ 3; 52% versus 25%), whereas ischemia with physical stress did not differ (36% versus 25%). In older patients, there were no sex differences in MSIMI. The higher prevalence of MSIMI in young women persisted when adjusting for sociodemographic and life-style factors, coronary artery disease severity, and depression. CONCLUSIONS: MSIMI post-MI is more common in women 50 years or younger compared with age-matched men. These sex differences are not observed in post-MI patients who are older than 50 years.

Obesity and Oral Health: The Link Between Adipokines and Periodontitis.

Periodontitis is a chronic inflammatory disease of the periodontium, or the supportive tissues around the tooth. This disease has been related to different risk factors, such as the presence of plaque and calculus, tobacco smoking, low socioeconomic status, and the immune state of the host. Importantly, the chronic inflammatory environment generated by periodontitis may lead to tooth loss and diverse systemic complications, such as cardiovascular disease, osteoarthritis and metabolic disease. Recent investigations have supported the role of obesity as a risk factor for periodontitis. Furthermore, studies have found obesity to compromise healing after periodontal therapy; however, the mechanisms underlying this association are not well understood. Proteins called 'adipokines' could be the factor linking obesity to periodontitis. Adipokines are bioactive molecules with hormonal properties and a structure similar to cytokines produced by the adipose tissue. Although adipokines have both pro-and anti-inflammatory effects, the shift towards pro-inflammatory actions occurs when the adipose tissue becomes pathological, as observe in the progression of conditions such as obesity or adiposopathy. This article reviews the role of adipokines in the pathophysiology and progression of periodontitis by focusing on their impact on inflammation and the molecular mechanisms through which adipokines contribute to the onset and development of periodontitis.

In silico medicine and -omics strategies in nephrology: contributions and relevance to the diagnosis and prevention of chronic kidney disease.

Chronic kidney disease (CKD) has been increasing over the last years, with a rate between 0.49% to 0.87% new cases per year. Currently, the number of affected people is around 850 million worldwide. CKD is a slowly progressive disease that leads to irreversible loss of kidney function, end-stage kidney disease, and premature death. Therefore, CKD is considered a global health problem, and this sets the alarm for necessary efficient prediction, management, and disease prevention. At present, modern computer analysis, such as in silico medicine (ISM), denotes an emergent data science that offers interesting promise in the nephrology field. ISM offers reliable computer predictions to suggest optimal treatments in a case-specific manner. In addition, ISM offers the potential to gain a better understanding of the kidney physiology and/or pathophysiology of many complex diseases, together with a multiscale disease modeling. Similarly, -omics platforms (including genomics, transcriptomics, metabolomics, and proteomics), can generate biological data to obtain information on gene expression and regulation, protein turnover, and biological pathway connections in renal diseases. In this sense, the novel patient-centered approach in CKD research is built upon the combination of ISM analysis of human data, the use of in vitro models, and in vivo validation. Thus, one of the main objectives of CKD research is to manage the disease by the identification of new disease drivers, which could be prevented and monitored. This review explores the wide-ranging application of computational medicine and the application of -omics strategies in evaluating and managing kidney diseases.

Evaluating Osteoporosis in Chronic Kidney Disease: Both Bone Quantity and Quality Matter.

Bone strength is determined not only by bone quantity [bone mineral density (BMD)] but also by bone quality, including matrix composition, collagen fiber arrangement, microarchitecture, geometry, mineralization, and bone turnover, among others. These aspects influence elasticity, the load-bearing and repair capacity of bone, and microcrack propagation and are thus key to fractures and their avoidance. In chronic kidney disease (CKD)-associated osteoporosis, factors traditionally associated with a lower bone mass (advanced age or hypogonadism) often coexist with non-traditional factors specific to CKD (uremic toxins or renal osteodystrophy, among others), which will have an impact on bone quality. The gold standard for measuring BMD is dual-energy X-ray absorptiometry, which is widely accepted in the general population and is also capable of predicting fracture risk in CKD. Nevertheless, a significant number of fractures occur in the absence of densitometric World Health Organization (WHO) criteria for osteoporosis, suggesting that methods that also evaluate bone quality need to be considered in order to achieve a comprehensive assessment of fracture risk. The techniques for measuring bone quality are limited by their high cost or invasive nature, which has prevented their implementation in clinical practice. A bone biopsy, high-resolution peripheral quantitative computed tomography, and impact microindentation are some of the methods established to assess bone quality. Herein, we review the current evidence in the literature with the aim of exploring the factors that affect both bone quality and bone quantity in CKD and describing available techniques to assess them.

The Placental Role in Gestational Diabetes Mellitus: A Molecular Perspective.

During pregnancy, women undergo several metabolic changes to guarantee an adequate supply of glucose to the foetus. These metabolic modifications develop what is known as physiological insulin resistance. When this process is altered, however, gestational diabetes mellitus (GDM) occurs. GDM is a multifactorial disease, and genetic and environmental factors play a crucial role in its aetiopathogenesis. GDM has been linked to both macroscopic and molecular alterations in placental tissues that affect placental physiology. This review summarizes the role of the placenta in the development of GDM from a molecular perspective, including hormonal and pro-inflammatory changes. Inflammation and hormonal imbalance, the characteristics dominating the GDM microenvironment, are responsible for placental changes in size and vascularity, leading to dysregulation in maternal and foetal circulations and to complications in the newborn. In conclusion, since the hormonal mechanisms operating in GDM have not been fully elucidated, more research should be done to improve the quality of life of patients with GDM and their future children.

Pancreatic and Hepatic Injury in COVID-19: A Worse Prognosis in NAFLD Patients?

The novel disease produced by SARS-CoV-2 mainly harms the respiratory tract, but it has shown the capacity to affect multiple organs. Epidemiologic evidence supports the relationship between Coronavirus Disease 2019 (COVID-19) and pancreatic and hepatic injury development, identified by alterations in these organ function markers. In this regard, it is important to ascertain how the current prevalence of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) might affect COVID-19 evolution and complications. Although it is not clear how SARS-CoV-2 affects both the pancreas and the liver, a multiplicity of potential pathophysiological mechanisms seem to be implicated; among them, a direct viral-induced injury to the organ involving liver and pancreas ACE2 expression. Additionally, immune system dysregulation, coagulopathies, and drugs used to treat the disease could be key for developing complications associated with the patient's clinical decline. This review aims to provide an overview of the available epidemiologic evidence regarding developing liver and pancreatic alterations in patients with COVID-19, as well as the possible role that NAFLD/NASH might play in the pathophysiological mechanisms underlying some of the complications associated with COVID-19. This review employed a comprehensive search on PubMed using relevant keywords and filters. From the initial 126 articles, those aligning with the research target were selected and evaluated for their methodologies, findings, and conclusions. It sheds light on the potential pathophysiological mechanisms underlying this relationship. As a result, it emphasises the importance of monitoring pancreatic and hepatic function in individuals affected by COVID-19.

Epicardial adipose tissue predicts mortality in incident hemodialysis patients: a substudy of the Renagel in New Dialysis trial.

BACKGROUND: Epicardial adipose tissue (EAT) has been described in the general population as an independent risk marker for incident coronary artery disease. In hemodialysis patients, it correlates with other markers of cardiovascular disease, but it is unknown if it is associated with adverse events. METHODS: post hoc analysis of the Renagel in New Dialysis (RIND) patients study, a randomized trial of sevelamer versus calcium-based phosphate binders in 109 incident hemodialysis patients, followed for all-cause mortality for a median of 49.3 months. Patients underwent baseline cardiac computed tomography imaging within 120 days of dialysis initiation. RESULTS: Baseline EAT measurements were available in 95 patients; EAT was positively correlated with age, body mass index, triglycerides, C-reactive protein, coronary artery calcium and aortic calcium, and negatively correlated with systolic and diastolic blood pressure, serum high density lipoprotein (HPL) cholesterol and serum phosphate (all P < 0.05). During follow-up, a total of 27 (28.4%) patients expired [mortality per 1000 patients/year: 95% confidence interval (95% CI) = 77 (64-94)]. Five-year survival rate was 44. 6% (95% CI: 21.1-65.7) and 71.2% (95% CI: 45.95-86.25) in patients with EAT above or below the median, respectively. Each 10 cc increase in EAT volume was associated with a significant 6% increase in the risk of death during follow-up [hazard ratio (HR): 1.060; 95% CI: 1.013-1.109; P-value = 0.012]. CONCLUSIONS: In this subanalysis of a randomized trial, EAT was an independent predictor of mortality in incident hemodialysis patients after ~4 years of follow-up. These hypothesis-generating findings will need confirmatory evidence.

Hybrid myocardial imaging for risk stratification prior to kidney transplantation: added value of coronary calcium and epicardial adipose tissue.

BACKGROUND: Patient selection and optimal approach to risk stratification prior to kidney transplantation remain uncertain. We sought new predictors of an abnormal myocardial perfusion (MYP) stress test result. METHODS: Retrospective study of 411 consecutive chronic kidney disease stages 4-5D patients awaiting kidney transplantation referred for risk stratification. PET-CT or SPECT-CT was used to assess MYP and quantify coronary artery calcium (CAC) and epicardial adipose tissue (EAT). Abnormal MYP was defined as a perfusion defect involving ≥5% of the left ventricular myocardium. RESULTS: Fixed or reversible MYP defects were present in 41 patients (10%). Male sex, smoking, and history of cardiovascular disease were more prevalent; age was higher and CAC and EAT were greater in patients with MYP defects than in those with normal MYP. On multivariate logistic regression, EAT and CAC were independent predictors of abnormal MYP while diabetes mellitus showed a borderline association (P = .08). EAT added incremental diagnostic value to a model including age, CAC and diabetes mellitus [AUC 0.73 (95% CI 0.64-0.81) to 0.76 (95% CI 0.68-0.84; P = .02)]. Furthermore, the model containing EAT showed improved diagnostic discrimination. CONCLUSIONS: Abnormal MYP on screening stress testing appears to be rare in patients awaiting kidney transplantation suggesting an excess of testing. EAT and CAC may help predict what patients are at higher risk of developing abnormalities of MYP under stress.

Exploring the Link between Cardiorenal and Metabolic Diseases.

The close link between metabolic diseases, such as obesity and diabetes mellitus, and cardiorenal disease can be attributed not only to direct risk factors, such as hypertension, but also to the intricate interplay of various pathophysiological processes [...].

Role of Gut Microbiome in Atherosclerosis: Molecular and Therapeutic Aspects.

Atherosclerosis is one of the most relevant and prevalent cardiovascular diseases of our time. It is one of the pathological entities that increases the morbidity and mortality index in the adult population. Pathophysiological connections have been observed between atherosclerosis and the gut microbiome (GM), represented by a group of microorganisms that are present in the gut. These microorganisms are vital for metabolic homeostasis in humans. Recently, direct and indirect mechanisms through which GM can affect the development of atherosclerosis have been studied. This has led to research into the possible modulation of GM and metabolites as a new target in the prevention and treatment of atherosclerosis. The goal of this review is to analyze the physiopathological mechanisms linking GM and atherosclerosis that have been described so far. We also aim to summarize the recent studies that propose GM as a potential target in atherosclerosis management.

Is S100B Involved in Attention-Deficit/Hyperactivity Disorder (ADHD)? Comparisons with Controls and Changes Following a Triple Therapy Containing Methylphenidate, Melatonin and ω-3 PUFAs.

BACKGROUND: Increasing evidence supports a neuroinflammatory basis in ADHD damaging glial function and thereby altering dopaminergic (DA) neurotransmission. Previous studies focusing on the S100B protein as a marker of glial function have shown contradictory results. We conducted a clinical trial to investigate differences in S100B levels between ADHD patients and controls, as well as observe gradual changes in S100B concentrations after a triple therapy (TT) containing methylphenidate (MPH), melatonin (aMT) and omega-3 fatty acids (ω-3 PUFAs). METHODS: 62 medication-naïve children with ADHD (ADHD-G) and 65 healthy controls (C-G) were recruited. Serum S100B was measured at baseline (T0) in ADHD-G/C-G, and three (T3) and six months (T6) after starting TT in the ADHD-G, together with attention scores. RESULTS: A significant increase in S100B was observed in the ADHD-G vs. C-G. In the ADHD-G, significantly higher S100B values were observed for comparisons between T0-T3 and between T0-T6, accompanied by a significant improvement in attention scores for the same timepoint comparisons. No significant differences were found for S100B between T3-T6. CONCLUSION: Our results agree with the hypothesis of glial damage in ADHD. Further studies on the link between DA and S100B are required to explain the transient increase in S100B following TT.