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.

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.

Retarding Progression of Chronic Kidney Disease in Autosomal Dominant Polycystic Kidney Disease with Metformin and Other Therapies: An Update of New Insights.

Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent single-gene disorder leading to renal failure. Current therapies are aimed to treat renal and extrarenal complications of ADPKD, but improved knowledge of the pathophysiological mechanisms leading to the generation and growth of cysts has permitted the identification of new drug candidates for clinical trials. Among these, in this review, we will examine above all the role of metformin, hypothesized to be able to activate the AMP-activated protein kinase (AMPK) pathway and potentially modulate some mechanisms implicated in the onset and the growth of the cysts.

Nephrosclerosis impacts time trajectory of renal function and outcomes in elderly individuals with chronic kidney disease.

Despite hypertension ranks among the leading causes of chronic kidney disease (CKD), the impact of chronic hypertensive nephropathy, the so-called 'nephrosclerosis' (NS), on CKD progression is often unpredictable, particularly in elderly population. We have conducted a prospective, observational study to define renal function patterns and outcomes in elderly CKD individuals with or without NS. Three hundred four individuals with an already established CKD were categorized according to the etiology of CKD. NS was defined as the presence of CKD associated with long-term essential hypertension, hypertensive retinopathy, left ventricular hypertrophy and minimal proteinuria. Time trajectories in estimated glomerular filtration rate (eGFR) (CKD-Epi) were computed over a 4-year follow-up. In addition, we analyzed the occurrence of a composite outcome of doubling of serum creatinine levels, eGFR reduction ≥25% and/or the need of chronic renal replacement therapy. CKD was secondary to nephrosclerosis (CKD-NS) in 220 (72.3%). In the whole cohort, the average estimated annual GFR slope was 1.8 mL/min/1.73 m2 eGFR decline was slower in CKD-NS as compared with others (1.4 vs 3.4 mL/min/1.73 m2; p<0.001). The composite renal outcome during follow-up occurred less frequently among elderly with CKD-NS (16/204 vs 14/70; p=0.01, crude HR 0.43, 95% CI 0.22 to 0.85) and was associated at logistic analyses with the etiology of CKD, background cardiovascular disease, total and low density lipoproteins (LDL) cholesterol, and glycemia levels (p value was ranging from 0.01 to 0.05). Despite being highly prevalent in the elderly, NS is associated with a more favorable renal disease course as compared with other conditions.