Sex and the veins. A cross-sectional analysis on sexual dysfunction in patients with Chronic Venous Disease.

Background: This study aimed to investigate the presence of sexual dysfunction (SD) in patients with Chronic Venous Disease (CVD) and if CVD treatments may have an impact on SD evolution in these patients. Methods: Inclusion criteria were patients of both sexes and genders, with minimum age of 18, with first diagnosis of CVD. Exclusion criteria were presence of known sexual dysfunction of organic origin, arterial system diseases, malignancies and endocrine system diseases. Included patients were administered the ASEX (Arizona Sexual Experience) questionnaire that was administered at the moment of study inclusion (T0), and for patients that resulted affected from sexual dysfunction, were administered also, after CVD treatments at 6 months (T1) and after 12 months (T2). Results: A total of 649 patients with CVD were recruited. After the administration of the ASEX questionnaire, 122 patients (18.8 %) resulted affected from SD. Female sex, C3-C6 clinical stages, and the presence of Coronary Artery Disease (CAD), hypertension, and hyperlipidemia were more associated with the presence of SD. SD improved in all patients' population, especially after CVD treatment at T2. Conclusions: CVD patients may experience SD, especially in female sex, in more advanced disease stages. SD in CVD patients appears to improve after adequate CVD treatment.

Urinary Post-Translationally Modified Fetuin-A (uPTM-FetA) in Chronic Kidney Disease Patients with and without Diabetic Kidney Disease.

Background and Objectives: A novel post-translational modification (PTM) fragment derived from the cleavage of Fetuin-A (PTM-FetA) has recently emerged as a sensitive biomarker for kidney damage in diabetic patients, but evidence in other chronic renal diseases is lacking. In this pilot study, we aimed at evaluating the clinical significance of urinary PTM-FetA (uPTM-FetA) in a mixed cohort of patients with non-advanced chronic kidney disease (CKD) secondary to diabetic kidney disease (DKD) or other causes. Materials and Methods: We enrolled 47 adult patients with CKD (mean CKD-Epi 40.10 ± 16.5 mL/min/1.73 m2) due to DKD (n = 34) or other etiology (n = 13). uPTM-FetA was measured in the urine using a commercially available ELISA kit. Fifteen healthy individuals served as controls. Results: Collectively, all CKD patients displayed remarkably higher levels of uPTM-FetA than controls (0.84 [0.10-1.15] vs. 29.68 [2.50-55.16] ng/mL p = 0.0005), but values were lower in non-DKD than in DKD patients (1.66 [0.09-4.19] vs. 13.9 [0.01-45.02] ng/mL; p = 0.01). uPTM-FetA showed a great diagnostic capacity at ROC analyses to identify the presence of CKD (AUC 0.776; p < 0.001) and, within CKD patients, to discriminate the diabetic and non-diabetic etiology (AUC 0.673; p = 0.02). At multivariate correlation analyses, proteinuria (ß = 0.442; p = 0.02) and BMI (ß = -0.334; p = 0.04) were the sole independent predictors of uPTM-FetA in this study population. Conclusions: uPTM-FetA could be a novel sensitive biomarker at the crossroad of chronic renal damage and metabolic dysfunction. Additionally, this biomarker could also represent a non-invasive, complementary tool for discriminating among different CKD etiologies (DKD vs. non-DKD) in difficult cases or when renal biopsy is not available.

Metalloproteinases as Biomarkers and Sociomarkers in Human Health and Disease.

Metalloproteinases (MPs) are zinc-dependent enzymes with proteolytic activity and a variety of functions in the pathophysiology of human diseases. The main objectives of this review are to analyze a specific family of MPs, the matrix metalloproteinases (MMPs), in the most common chronic and complex diseases that affect patients' social lives and to better understand the nature of the associations between MMPs and the psychosocial environment. In accordance with the PRISMA extension for a scoping review, an examination was carried out. A collection of 24 studies was analyzed, focusing on the molecular mechanisms of MMP and their connection to the manifestation of social aspects in human disease. The complexity of the relationship between MMP and social problems is presented via an interdisciplinary approach based on complexity paradigm as a new approach for conceptualizing knowledge in health research. Finally, two implications emerge from the study: first, the psychosocial states of individuals have a profound impact on their overall health and disease conditions, which implies the importance of adopting a holistic perspective on human well-being, encompassing both physical and psychosocial aspects. Second, the use of MPs as biomarkers may provide physicians with valuable tools for a better understanding of disease when used in conjunction with "sociomarkers" to develop mathematical predictive models.

Spice Up Your Kidney: A Review on the Effects of Capsaicin in Renal Physiology and Disease.

Capsaicin, the organic compound which attributes the spicy flavor and taste of red peppers and chili peppers, has been extensively studied for centuries as a potential natural remedy for the treatment of several illnesses. Indeed, this compound exerts well-known systemic pleiotropic effects and may thus bring important benefits against various pathological conditions like neuropathic pain, rhinitis, itching, or chronic inflammation. Yet, little is known about the possible biological activity of capsaicin at the kidney level, as this aspect has only been addressed by sparse experimental investigations. In this paper, we aimed to review the available evidence focusing specifically on the effects of capsaicin on renal physiology, as well as its potential benefits for the treatment of various kidney disorders. Capsaicin may indeed modulate various aspects of renal function and renal nervous activity. On the other hand, the observed experimental benefits in preventing acute kidney injury, slowing down the progression of diabetic and chronic kidney disease, ameliorating hypertension, and even delaying renal cancer growth may set the stage for future human trials of capsaicin administration as an adjuvant or preventive therapy for different, difficult-to-treat renal diseases.

Evaluation of arteriovenous fistula for hemodialysis with a new generation digital stethoscope: a pilot study.

BACKGROUND AND AIMS: The management of complications of arteriovenous fistula (AVF) for hemodialysis, principally stenosis, remains a major challenge for clinicians with a substantial impact on health resources. Stenosis not infrequently preludes to thrombotic events with the loss of AVF functionality. A functioning AVF, when listened by a stethoscope, has a continuous systolic-diastolic low-frequency murmur, while with stenosis, the frequency of the murmur increases and the duration of diastolic component decreases, disappearing in severe stenosis. These evidences are strictly subjective and dependent from operator skill and experience. New generation digital stethoscopes are able to record sound and subsequently dedicated software allows to extract quantitative variables that characterize the sound in an absolutely objective and repeatable way. The aim of our study was to analyze with an appropriate software sounds from AVFs taken by a commercial digital stethoscope and to investigate the potentiality to develop an objective way to detect stenosis. METHODS: Between September 2022 and January 2023, 64 chronic hemodialysis (HD) patients were screened by two blinded experienced examiners for recognized criteria for stenosis by Doppler ultrasound (DUS) and, consequently, the sound coming from the AVFs using a 3 M™ Littmann® CORE Digital Stethoscope 8570 in standardized sites was recorded. The sound waves were transformed into quantitative variables (amplitude and frequency) using a sound analysis software. The practical usefulness of the core digital stethoscope for a quick identification of an AVF stenosis was further evaluated through a pragmatic trial. Eight young nephrologist trainees underwent a simple auscultatory training consisting of two sessions of sound auscultation focusing two times on a "normal" AVF sound by placing the digital stethoscope on a convenience site of a functional AVF. RESULTS: In 48 patients eligible, all sound components displayed, alone, a remarkable diagnostic capacity. More in detail, the AUC of the average power was 0.872 [95% CI 0.729-0.951], while that of the mean normalized frequency was 0.822 [95% 0.656-0.930]. From a total of 32 auscultations (eight different block sequences, each one comprising four auscultations), the young clinicians were able to identify the correct sound (stenosis/normal AVF) in 25 cases, corresponding to an overall accuracy of 78.12% (95% CI 60.03-90.72%). CONCLUSIONS: The analysis of sound waves by a digital stethoscope permitted us to distinguish between stenotic and no stenotic AVFs. The standardization of this technique and the introducing of data in a deep learning algorithm could allow an objective and fast method for a frequent monitoring of AVF.

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.

Childhood Obesity: Insight into Kidney Involvement.

This review examines the impact of childhood obesity on the kidney from an epidemiological, pathogenetic, clinical, and pathological perspective, with the aim of providing pediatricians and nephrologists with the most current data on this topic. The prevalence of childhood obesity and chronic kidney disease (CKD) is steadily increasing worldwide, reaching epidemic proportions. While the impact of obesity in children with CKD is less pronounced than in adults, recent studies suggest a similar trend in the child population. This is likely due to the significant association between obesity and the two leading causes of end-stage renal disease (ESRD): diabetes mellitus (DM) and hypertension. Obesity is a complex, systemic disease that reflects interactions between environmental and genetic factors. A key mechanism of kidney damage is related to metabolic syndrome and insulin resistance. Therefore, we can speculate about an adipose tissue-kidney axis in which neurohormonal and immunological mechanisms exacerbate complications resulting from obesity. Adipose tissue, now recognized as an endocrine organ, secretes cytokines called adipokines that may induce adaptive or maladaptive responses in renal cells, leading to kidney fibrosis. The impact of obesity on kidney transplant-related outcomes for both donors and recipients is also significant, making stringent preventive measures critical in the pre- and post-transplant phases. The challenge lies in identifying renal involvement as early as possible, as it is often completely asymptomatic and not detectable through common markers of kidney function. Ongoing research into innovative technologies, such as proteomics and metabolomics, aims to identify new biomarkers and is constantly evolving. Many aspects of pediatric disease progression in the population of children with obesity still require clarification. However, the latest scientific evidence in the field of nephrology offers glimpses into various new perspectives, such as genetic factors, comorbidities, and novel biomarkers. Investigating these aspects early could potentially improve the prognosis of these young patients through new diagnostic and therapeutic strategies. Hence, the aim of this review is to provide a comprehensive exploration of the pathogenetic mechanisms and prevalent pathological patterns of kidney damage observed in children with obesity.

Circulating miRNA 122-5p Expression Predicts Mortality and Cardiovascular Events in Chronic Hemodialysis Patients: A Multicentric, Pilot, Prospective Study.

BACKGROUND: Despite patients undergoing chronic hemodialysis (HD) being notoriously prone to adverse cardiovascular (CV) events, risk prediction in this population remains challenging. miRNA 122-5p, a short, non-coding RNA predominantly involved in lipid and carbohydrate metabolism, has recently been related to the onset and progression of CV disease. METHODS: We run a pilot, multicenter, longitudinal, observational study to evaluate the clinical significance and prognostic usefulness of circulating miRNA 122-5p in a multicentric cohort of 74 individuals on maintenance HD. RESULTS: Patients displayed lower circulating miRNA 122-5p as compared to healthy controls (p = 0.004). At correlation analyses, ALT (ß = 0.333; p = 0.02), E/e' (ß = 0.265; p = 0.02) and CRP (ß = -0.219; p = 0.041) were independent predictors of miRNA 122-5p levels. During a median follow-up of 22 months (range of 1-24), 30 subjects (40.5%) experienced a composite endpoint of all-cause mortality and fatal/non-fatal CV events. Baseline circulating miRNA 122-5p was higher in these subjects (p = 0.01) and it predicted a significantly higher risk of endpoint occurrence (Kaplan-Meier crude HR 3.192; 95% CI 1.529-6.663; p = 0.002; Cox regression adjusted HR 1.115; 95% CI 1.009-1.232; p = 0.03). CONCLUSIONS: Altered miRNA 122-5p levels in HD patients may reflect hepatic and CV damage and may impart important prognostic information for improving CV risk prediction in this particular setting.

Self-Reported Physical Inactivity and Mood Disturbances in End-Stage Kidney Disease (ESKD) Patients on Chronic Dialysis Treatment.

BACKGROUND: Physical inactivity and mood disturbances are key issues in individuals with end-stage kidney disease (ESKD) and may lead to poor clinical outcomes. METHODS: We performed a pilot, observational study to explore the possible relationships between the self-reported level of physical activity (IPAQ) and the severity of mood disturbances (BDI score) in a cohort of 58 ESKD patients undergoing chronic hemodialysis (HD; n = 30) or peritoneal dialysis (PD; n = 28). RESULTS: Overall, ESKD patients were severely inactive (median METs: 590 [460-1850]) and the intensity of overall and walking physical activity was mostly low to moderate. HD individuals appeared less active than PD (METs 550 [250-1600] vs. 1080 [750-1730]; p = 0.003) and were also less prone to walking (METs 180 ± 90 vs. 320 ± 100; p = 0.01), while a barely statistical difference was noticed for the time spent sitting. ESKD individuals displayed a median BDI score of 17 [12-21], which indicated, on average, the presence of borderline depression, which was apparently more evident among HD individuals. A strong, inverse correlation was found between self-reported METs and BDI scores (R = -0.78; p < 0.0001), while such scores paralleled the time spent sitting during a weekday (R = 0.45; p = 0.0004) and a weekend day (R = 0.40; p = 0.002). CONCLUSIONS: In ESKD patients on chronic dialysis, physical inactivity and mood disturbances might be significantly inter-connected, thereby amplifying their relative impact on quality of life, dysautonomia and long-term outcomes. Future studies on larger populations are recommended to confirm these preliminary observations. Promoting strategies to improve fitness, along with greater attention to physiological aspects, should be incorporated into the clinical management of ESKD patients.

Hyperkalemia in CKD: an overview of available therapeutic strategies.

Hyperkalemia (HK) is a life-threatening condition that often occurs in patients with chronic kidney disease (CKD). High serum potassium (sKsK) is responsible for a higher risk of end-stage renal disease, arrhythmias and mortality. This risk increases in patients that discontinue cardio-nephroprotective renin-angiotensin-aldosterone system inhibitor (RAASi) therapy after developing HK. Hence, the management of HK deserves the attention of the clinician in order to optimize the therapeutic strategies of chronic treatment of HK in the CKD patient. The adoption in clinical practice of the new hypokalaemic agents patiromer and sodium zirconium cyclosilicate (SZC) for the prevention and chronic treatment of HK could allow patients, suffering from heart failure and chronic renal failure, to continue to benefit from RAASi therapy. We have updated a narrative review of the clear variables, correct definition, epidemiology, pathogenesis, etiology and classifications for HK among non-dialysis CKD (ND CKD) patients. Furthermore, by describing the prognostic impact on mortality and on the progression of renal damage, we want to outline the strategies currently available for the control of potassium (K+) plasma levels.

Urinary Marinobufagenin in Patients with Non-Advanced Chronic Kidney Disease: A Cross-Sectional Study.

Background and Objectives: The global prevalence of chronic kidney disease (CKD) is on the rise, posing important challenges for healthcare systems. Thus, the search for new factors potentially involved in the pathogenesis, progression and complications of early CKD remains urgent. Marinobufagenin (MBG) is a natriuretic endogenous cardiotonic steroid, and increased circulating levels of it may accelerate kidney damage. In this study, we explored the possible clinical significance of measuring urinary marinobufagenin (uMBG) in patients with non-advanced CKD. Materials and Methods: One hundred and eight adult CKD patients (mean age 71.6 ± 10 years, 70.4% male; mean eGFR 40.54 ± 17 mL/min/1.73 m2) were enrolled in this cross-sectional study. uMBG was measured together with a series of clinical, anthropometric, laboratory and instrumental analyses. Twenty-five healthy matched subjects served as controls for the uMBG measurement. Results: The uMBG values were lower in the patients with CKD as compared to those of the controls (0.37 [IQR: 0.25-0.45] vs. 0.64 [0.46-0.78] nmol/L. p = 0.004), and a significant trend in eGFR levels was noticed across the decreasing uMBG tertiles (p = 0.03). Regarding the correlation analyses, the uMBG values remained robustly associated with the eGFR in multivariate models employing either uMBG or eGFR as the dependent variable (ß = 0.248; p = 0.01 and ß = 0.139; p = 0.04, respectively). Besides the eGFR, the independent predictors of uMBG values in this population were the use of statins (ß = -0.326; p = 0.001), the presence of diabetes (ß = 0.243; p = 0.009) and urine sodium (ß = 0.204; p = 0.01). Conclusions: Reduced uMBG excretion may reflect impaired renal clearance, which may contribute to the detrimental effects attributed to this hormone due to systemic accumulation. Future studies are needed to clarify the biological mechanisms placing uMBG at the crossroad of sodium intake and the presence of diabetes in CKD-suffering individuals and to verify whether a statin treatment may somewhat limit the detrimental effects of MBG in the presence of impaired renal function.

New Insights on the Role of Marinobufagenin from Bench to Bedside in Cardiovascular and Kidney Diseases.

Marinobufagenin (MBG) is a member of the bufadienolide family of compounds, which are natural cardiac glycosides found in a variety of animal species, including man, which have different physiological and biochemical functions but have a common action on the inhibition of the adenosine triphosphatase sodium-potassium pump (Na+/K+-ATPase). MBG acts as an endogenous cardiotonic steroid, and in the last decade, its role as a pathogenic factor in various human diseases has emerged. In this paper, we have collated major evidence regarding the biological characteristics and functions of MBG and its implications in human pathology. This review focused on MBG involvement in chronic kidney disease, including end-stage renal disease, cardiovascular diseases, sex and gender medicine, and its actions on the nervous and immune systems. The role of MBG in pathogenesis and the development of a wide range of pathological conditions indicate that this endogenous peptide could be used in the future as a diagnostic biomarker and/or therapeutic target, opening important avenues of scientific research.

A Rare Complication of Ascariasis: A Case of Acute Interstitial Nephritis.

Acute interstitial nephritis (AIN) due to helminths is a rare cause of acute kidney injury (AKI). Helminthiases often progresses insidiously, making diagnosis difficult. This was the case of a 72-year-old man, who presented with renal failure, itching and diarrhoea. Urinalysis revealed leukocyturia, microhaematuria and mild proteinuria. A full blood count revealed leucocytosis with eosinophilia. A stool parasitological examination revealed fertilised eggs of Ascaris lumbricoides. Tubulointerstitial nephropathy secondary to A. lumbricoides infection was suspected. A percutaneous renal biopsy was not performed since the patient refused the anti-platelet therapy discontinuation. Mebendazole, albendazole and prednisone therapy was administered. After worm eradiation and discharge, recovery from the parasitosis, absence of pruritus and eosinophilia, and progressive improvement of renal function were observed, strongly suggesting a causal relationship between Ascaris infection and AIN. Parasite infection should be considered in the differential diagnosis of unexplained renal failure because early diagnosis and treatment are necessary to avoid irreversible complications.

Risk Factors for Bleeding Varicose Veins in Patients with Chronic Venous Disease.

Background and Objectives: Chronic venous disease (CVD) is a widespread clinical condition that is very common in western countries in the adult general population with a wide range of clinical manifestations, such as varicose veins (VVs) that in certain circumstances may complicate with rupture and subsequent bleeding that may even be fatal. The aim of this study is to evaluate risk factors for bleeding VVs. Materials and Methods: This is a retrospective study conducted in patients with CVD complicating with bleeding of VVs over a 4-year period (2019-2022). A random sample, for the same 4-year period and with a 3:1 ratio, was selected from other CVD patients without VVs bleeding that served as the control group. Results: From a global population of 1048 patients with CVD over a 4-year period, a total of 33 patients (3.15%) with VVs bleeding were selected. A group of 99 patients without VVs bleeding were randomly selected from the total population of 1048 patients with CVD. Findings of this study showed that advanced clinical stage of CVD (i.e., C4b stage), advanced age, living alone, suffering from cardiovascular co-morbidity (i.e., hypertension and CHF), assuming certain drugs that act on blood coagulation (i.e., aspirin, anticoagulants), assuming psychotropic medication, having particular venous reflux patterns (i.e., below-knee GSV reflux, non-saphenous veins reflux, Cockett's perforators reflux), and not having been assessed and treated previously for CVD (i.e., with VADs, CT, or surgery) may predispose a high risk for bleeding VVs. Conclusions: Bleeding VVs may be a life-threatening complications of CVD patients, and monitoring risk factors found in this study and others that, hopefully, may be discovered in the future through further focused research will help to reduce the impact of this problem in this patient population.

A small circulating miRNAs signature predicts mortality and adverse cardiovascular outcomes in chronic hemodialysis patients.

Background: Chronic hemodialysis (HD) patients exhibit severe morpho-functional cardiac alterations, putting them at a high risk of death and adverse cardiovascular (CV) outcomes. Despite the fact that an unbalanced expression of various microRNAs (miRNAs) has been related to pathological cardiac remodeling and worse CV outcomes, scarce evidence exists on their role in this setting. Methods: We evaluated circulating levels of a selected miRNAs panel (30a-5p, 23a-3p, 451a and let7d-5p) in 74 chronic HD patients together with a thorough clinical and echocardiography assessment. Individuals were then prospectively followed (median 22 months). The primary endpoint was a composite of all-cause and CV mortality and non-fatal CV events. Results: Circulating levels of all miRNAs were lower in HD patients as compared with healthy controls and independently correlated to the severity of cardiac dysfunction. miRNA 30a-5p, 23a-3p and 451a expression was even lower in 30 subjects (40.5%) reaching the composite endpoint (P < .001), while no differences were reported for let7d-5p. The predictive value of these miRNAs was supported by univariate followed by multivariate Cox regression analyses [hazard ratio (HR) ranging from 0.943 to 0.995; P = .05 to .02] while Kaplan-Meier analyses confirmed a faster progression to the endpoint in individuals displaying miRNA levels below an optimal receiver operating characteristic-derived cut-off value (P ranging from .001 to <.0001; crude HRs 7.95 to 8.61). Conclusions: Lower circulating levels of miRNA 30-5p, 23a-3p and 451a in HD patients may reflect cardiac abnormalities and predict a higher risk of worse clinical outcomes in the short mid-term. Future studies on larger HD populations are needed to generalize these findings.

The Impact of Cholecaciferol Supplementation on Bone Mineral Density in Long-Term Kidney Transplant Recipients.

Although reduced bone mineral density (BMD) is associated with a higher risk of fractures, morbidity, and mortality in kidney transplant patients (KTRs), there is no consensus on optimal treatment for the alterations of BMD in this population. This study aims at assessing the effect of cholecalciferol supplementation on BMD over a follow-up period of 2 years in a cohort of long-term KTRs. Patients with age ≥ 18 years were included and divided into two subgroups based on treatment with bisphosphonate and/or calcimimetics and/or active vitamin D sterols (KTRs-treated) or never treated with the above medications (KTRs-free). BMD was evaluated at lumbar vertebral bodies (LV) and right femoral neck (FN) with standard DEXA at the beginning and end of the study. According to World Health Organization (WHO) criteria, results were expressed as T-score and Z-score. Osteoporosis and osteopenia were defined as T score ≤ -2.5 SD and T score < -1 and >-2.5 SD, respectively. Cholecalciferol was supplemented at a dose of 25,000 IU/week over 12 weeks followed by 1500 IU/day. KTRs-free (n. 69) and KTRs-treated (n. 49) consecutive outpatients entered the study. KTRs-free were younger (p < 0.05), with a lower prevalence of diabetes (p < 0.05) and of osteopenia at FN (46.3 % vs. 61.2 %) compared to KTRs-treated. At the entry none of the study subjects had a sufficient level of cholecalciferol; Z-score and T-score at LV and FN were not different between groups. At the end of the study period, serum cholecalciferol concentration was significantly increased in both groups (p < 0.001); the KTRs-free group presented an improvement in both T-score and Z-score at LV (p < 0.05) as well as a lower prevalence of osteoporotic cases (21.7% vs. 15.9%); in contrast, no changes were recorded in KTR-treated individuals. In conclusion, supplementation with cholecalciferol ameliorated Z-score and T-score at LV in long-term KTRs who had been never treated with active or inactive vitamin D sterols, bisphosphonates, and calcimimetics. Future endeavours are needed to confirm these preliminary findings.

Metalloproteinases and Hypertrophic Cardiomyopathy: A Systematic Review.

Hypertrophic cardiomyopathy (HCM) is a genetic condition determined by an altered collagen turnover of the extracellular matrix. Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) are abnormally released in patients with HCM. The purpose of this systematic review was to thoroughly summarize and discuss the existing knowledge of MMPs profile in patients with HCM. All studies meeting the inclusion criteria (detailed data regarding MMPs in patients with HCM) were selected, after screening the literature from July 1975 to November 2022. Sixteen trials that enrolled a total of 892 participants were included. MMPs-particularly MMP2-levels were found higher in HCM patients compared to healthy subjects. MMPs were used as biomarkers after surgical and percutaneous treatments. Understanding the molecular processes that control the cardiac ECM's collagen turnover allows for a non-invasive evaluation of HCM patients through the monitoring of MMPs and TIMPs.

Marinobufagenin, Left Ventricular Hypertrophy and Residual Renal Function in Kidney Transplant Recipients.

BACKGROUND: Left ventricular hypertrophy (LVH), which is a pervasive complication of end-stage kidney disease (ESKD), persists in some uremic individuals even after kidney transplantation (Ktx), contributing to worsening CV outcomes. Marinobufagenin (MBG), an endogenous steroid cardiotonic hormone endowed with natriuretic and vasoconstrictive properties, is an acknowledged trigger of uremic cardiomyopathy. However, its clinical significance in the setting of Ktx remains undefined. METHODS: In a cohort of chronic Ktx recipients (n = 40), we assessed circulating MBG together with a thorough clinical and echocardiographic examination. Forty matched haemodialysis (HD) patients and thirty healthy subjects served as controls for MBG measurements. Patients were then prospectively followed up to 12 months and the occurrence of an established cardio-renal endpoint (death, CV events, renal events, graft rejection) was recorded. RESULTS: Median MBG plasma levels were lower in Ktx as compared with HD patients (p = 0.02), but higher as compared with healthy controls (p = 0.0005). Urinary sodium (ß = 0.423; p = 0.01) and eGFR (ß = -0.324; p = 0.02) were the sole independent predictors of MBG in this cohort, while a strong correlation with left ventricular mass index (LVMi), found in univariate analyses (R = 0.543; p = 0.0007), gained significance only in multivariate models not including eGFR. Logistic regression analyses indicated MBG as a significant predictor of the combined endpoint (OR 2.38 [1.10-5.12] per each 1 nmoL/L increase; p = 0.01), as well as eGFR, LVMi, serum phosphate and proteinuria. CONCLUSIONS: Ktx recipients display altered MBG levels which are influenced by sodium balance, renal impairment and the severity of LVH. Thus, MBG might represent an important missing link between reduced graft function and pathological cardiac remodelling and may hold important prognostic value for improving cardio-renal risk assessment.

Vascular Biology of Arterial Aneurysms.

BACKGROUND: This review aims to analyze biomolecular and cellular events responsible for arterial aneurysm formation with particular attention to vascular remodeling that determines the initiation and the progression of arterial aneurysm, till rupture. METHODS: This review was conducted searching libraries such as Web of Science, Scopus, ScienceDirect, and MEDLINE. Used keywords with various combinations were "arterial aneurysms," "biology," "genetics," "proteomics," "molecular," "pathophysiology," and extracellular matrix". RESULTS: There are several genetic alterations responsible of syndromic and nonsyndromic disease that predispose to aneurysm formation. Extracellular matrix imbalance, mainly due to the alteration of vascular smooth muscle cells homeostasis, overexpression of metalloproteinases, and cytokines activation, determines weakness of the arterial wall that dilates thus causing aneurysmal disease. Altered mechanotransduction in the extracellular matrix may also trigger and sustain anomalous cellular and biochemical signaling. Different cell population such as vascular smooth muscle cells, macrophages, perivascular adipose tissue cells, and vascular wall resident stem cells are all involved at different levels. CONCLUSIONS: Improving knowledge in vascular biology may help researchers and physicians in better targeting aneurysmal disease to better prevent and better treat such important disease.

miRNAs in Uremic Cardiomyopathy: A Comprehensive Review.

Uremic Cardiomyopathy (UCM) is an irreversible cardiovascular complication that is highly pervasive among chronic kidney disease (CKD) patients, particularly in End-Stage Kidney Disease (ESKD) individuals undergoing chronic dialysis. Features of UCM are an abnormal myocardial fibrosis, an asymmetric ventricular hypertrophy with subsequent diastolic dysfunction and a complex and multifactorial pathogenesis where underlying biological mechanisms remain partly undefined. In this paper, we reviewed the key evidence available on the biological and clinical significance of micro-RNAs (miRNAs) in UCM. miRNAs are short, noncoding RNA molecules with regulatory functions that play a pivotal role in myriad basic cellular processes, such as cell growth and differentiation. Deranged miRNAs expression has already been observed in various diseases, and their capacity to modulate cardiac remodeling and fibrosis under either physiological or pathological conditions is well acknowledged. In the context of UCM, robust experimental evidence confirms a close involvement of some miRNAs in the key pathways that are known to trigger or worsen ventricular hypertrophy or fibrosis. Moreover, very preliminary findings may set the stage for therapeutic interventions targeting specific miRNAs for ameliorating heart damage. Finally, scant but promising clinical evidence may suggest a potential future application of circulating miRNAs as diagnostic or prognostic biomarkers for improving risk stratification in UCM as well.