A journey from microenvironment to macroenvironment: The role of metaflammation and epigenetic changes in cardiorenal disease

Chronic non-communicable diseases have become a pandemic public problem in the 21st century, causing enormous burden on the economy, health and quality of life of societies. The role of a chronic inflammatory state in the pathogenesis of chronic disease has been more comprehensively recognized by recent findings. The new paradigm 'metaflammation' focuses on metabolism-induced (high fat or fructose-based diet or excessive calorie intake) chronic inflammation. There is a close correlation between the increased incidence of chronic kidney disease (CKD) and chronic heart failure with both increased inflammatory marker levels and western-type diet. In this review we describe the concept of metaflammation, its role in the development of CKD and chronic heart disease, the molecular and signalling pathways involved and the therapeutic consequencesResearch by A.O. was funded by FIS ISCIII FEDER funds PI16/02057, ISCIII-RETIC REDinREN RD16/0009, EUTOX, Comunidad de Madrid en Biomedicina B2017/BMD-3686 CIFRA2-C

Evaluation of repeat distal transradial access in the anatomic snuffbox

PurposeThere is increasing interest in the distal radial artery in the anatomic snuffbox as an alternative arterial access point, but the durability of the distal radial artery to support repetitive accesses over multiple procedures is not well established. The purpose of this study was therefore to evaluate success rates for repeated left-sided distal transradial access (ldTRA) in the anatomic snuffbox.MethodsIn this single institution retrospective study, all patients undergoing radioembolization treatments from January 1st, 2019 to May 1st, 2020 were prospectively evaluated for ldTRA. ldTRA was performed by 15 different operators. Exclusion criteria were a left radiocephalic hemodialysis fistula, inability to properly position the arm, Barbeau D waveform, or failed prior ldTRA due to tortuosity. Barbeau patterns, arterial sizes, and success rates at the first, second, and third ldTRA were compared.ResultsFifty patients were evaluated for ldTRA and 44, 39, and 10 underwent one, two, and three ldTRA attempts for a total of 93 procedures. There was no significant change in Barbeau patterns between the first and second (p = 0.13) or first and third (p = 1.0) ldTRA. There was no significant change in artery size between the first (mean, 2.3 mm; range, 1.5–3.4 mm) and second (mean, 2.3 mm; range, 1.6–3.3 mm) (p = 0.59) and first and third (mean, 2.4 mm; range, 1.9–3.3) (p = 0.45) ldTRA. The success rate was not significantly different between the first (93%, 41/44, 95% CI 81%–99%), second (95%, 37/39, 95% CI 83%–99%), and third (100%, 10/10, 95% CI 69%–100%) procedure (p = 1.0). The asymptomatic occlusion rate was 4.1% (2/49, 95% CI 0%–14%), and subsequent ldTRA was successfully completed in both patients with occlusions. There were no hemorrhagic or ischemic complications.ConclusionSuccess rates are indistinguishable among first, second, and third time ldTRA suggesting that this is a durable access point

Future of kidney imaging: Functional magnetic resonance imaging and kidney disease progression

INTRODUCTION: Chronic kidney disease (CKD) which is a common cause of death has an increasing trend, but there is no established approach for predicting CKD progression yet. Functional magnetic resonance imaging (fMRI) studies such as blood oxygenation level-dependent MRI (BOLD-MRI), diffusion-weighted MRI (DWI-MRI), diffusion-tensor MRI (DTI-MRI) and arterial spin labelling MRI (ASL-MRI) are rising methods for the assessment of kidney functions in native and transplanted kidneys as well as the estimation of CKD progression. METHODS: Systematic literature review was performed through the Embase (Elsevier), Cochrane Central Register of Controlled Trials (Wiley), PubMed/Medline and Web of Science databases, and studies investigating the role of fMRI methods assessing kidney functions in native and transplanted kidneys, as well as the value of fMRI methods to predict CKD progression, were included. Working mechanisms, advantages and limitations of the fMRI modalities were reviewed, and three studies investigating the role of fMRI studies in kidney functions were analysed. RESULTS AND CONCLUSION: BOLD-MRI signal was found to be inversely correlated with annual eGFR change, and DWI/ADC (apparent diffusion coefficient map) values were shown to be correlated with annual eGFR decline. fMRI methods which are currently used for other systems can be utilized to provide more detailed information about kidney functions, and doctors should be ready to interpret kidney MRIs

Fatty Kidney: A Possible Future for Chronic Kidney Disease Research.

BACKGROUND: Metabolic syndrome is a growing twenty-first century pandemic associated with multiple clinical comorbidities ranging from cardiovascular diseases, non-alcoholic fatty liver disease and polycystic ovary syndrome to kidney dysfunction. A novel area of research investigates the concept of fatty kidney in the pathogenesis of chronic kidney disease, especially in patients with diabetes mellitus or metabolic syndrome. AIM: To review the most updated literature on fatty kidney and provide future research, diagnostic and therapeutic perspectives on a disease increasingly affecting the contemporary world. MATERIALS AND METHOD: We performed an extensive literature search through three databases including Embase (Elsevier) and the Cochrane Central Register of Controlled Trials (Wiley) and PubMed/Medline Web of Science in November 2021 by using the following terms and their combinations: \u27fatty kidney\u27, \u27ectopic fat\u27, \u27chronic kidney disease\u27, \u27cardiovascular event\u27, \u27cardio-metabolic risk\u27, \u27albuminuria\u27 and \u27metabolic syndrome\u27. Each study has been individually assessed by the authors. RESULTS: Oxidative stress and inflammation, Klotho deficiency, endoplasmic reticulum stress, mitochondrial dysfunction and disruption of cellular energy balance appear to be the main pathophysiological mechanisms leading to tissue damage following fat accumulation. Despite the lack of large-scale comprehensive studies in this novel field of research, current clinical trials demonstrate fatty kidney as an independent risk factor for the development of chronic kidney disease and cardiovascular events. CONCLUSION: The requirement for future studies investigating the pathophysiology, clinical outcomes and therapeutics of fatty kidney is clear

Serum glycated albumin predicts all-cause mortality in dialysis patients with diabetes mellitus: meta-analysis and systematic review of a predictive biomarker

Background and Aim: HbA1c, the traditional and current gold standard biomarker guiding diabetic management, has been scrutinized for low predictive value for patients with chronic kidney disease due to variables affecting erythrocyte number and turnover. Glycated albumin, the precursor to advanced glycation end products, reflects glycemic status over the preceding 2–3 week period and already outperforms HbA1c for glycemic monitoring. Our aim was to establish whether serum GA can be further used to predict mortality risk in dialysis patients with diabetes mellitus (DM) Methods: We did systematic review of the literature in PubMed/Medline, Web of Science, Embase (Elsevier) and the Cochrane Central Register of Controlled Trials (Wiley) up to and including February 2020. Results: This meta-analysis included 25,932 dialysis patients across 12 studies with maximum follow-up of 11 years. Higher GA levels were associated with the risk of all-cause mortality in dialysis patients with DM (HR 1.02, 95% CI 1.01 to 1.03, P < 0.001) irrespective of the type of dialysis, whereas higher GA was not associated with cardiovascular mortality (HR 1.03, 95% CI 0.99 to 1.06, P = 0.15) and cardiovascular events (both fatal and non-fatal) (HR 1.03, 95% CI 0.97 to 1.09, P = 0.31) in dialysis patients with DM. Conclusion: Serum glycated albumin predicts all-cause mortality risk in dialysis patients with DM. The endpoints of cardiovascular mortality and cardiovascular events trended similarly, but did not reach significance at the current sample size

The Effect of Urine pH and Urinary Uric Acid Levels on the Development of Contrast Nephropathy

Background: Hyperuricemia may cause acute kidney injury by activating inflammatory, pro-oxidative and vasoconstrictive pathways. In addition, radiocontrast causes an acute uricosuria, potentially leading to crystal formation. We therefore aimed to investigate the effect of urine acidity and urine uric acid level on the development of contrast-induced nephropathy (CIN) in patients undergoing elective coronary angiography. Methods: We enrolled 175 patients who underwent elective coronary angiography. CIN was defined as a >25% increase in the serum creatinine levels relative to basal values 48–72 h after contrast use. Prior to coronary angiography and 48–72 h later, serum uric acid, urea, creatinine, bicarbonate levels, and spot uric acid to creatinine ratio (UACR) were measured. Results: Of the 175 subjects included, 29 (16.6%) developed CIN. Those who developed CIN had a higher prevalence of diabetes, higher UACR (0.60 vs. 0.44, p = 0.014), higher contrast volume, and lower serum sodium level. With univariate analysis of a logistic regression model, the risk of CIN was found to be associated with diabetes (p = 0.0016, OR = 3.8 [95% CI: 1.7–8.7]), urine UACR (p = 0.0027, OR = 9.6 [95% CI: 2.2–42.2]), serum sodium (p = 0.0079, OR = 0.8 [95% CI: 0.77–0.96]), and contrast volume (p = 0.0385, OR = 1.8 [95% CI: 1.03–3.09]). In a multiple logistic regression model with stepwise method of selection, diabetes (p = 0.0120, OR = 3.2 [95% CI: 1.3–8.1]) and UACR (p = 0.0163, OR = 6.9 [95% CI: 1.4–33.4]) were the 2 risk factors finally identified. Conclusions: We have demonstrated that higher urine UACR is associated with the development of CIN in patients undergoing elective coronary angiography

Polymer-assisted intratumoral delivery of ethanol: Preclinical investigation of safety and efficacy in a murine breast cancer model.

Focal tumor ablation with ethanol could provide benefits in low-resource settings because of its low overall cost, minimal imaging technology requirements, and acceptable clinical outcomes. Unfortunately, ethanol ablation is not commonly utilized because of a lack of predictability of the ablation zone, caused by inefficient retention of ethanol at the injection site. To create a predictable zone of ablation, we have developed a polymer-assisted ablation method using ethyl cellulose (EC) mixed with ethanol. EC is ethanol-soluble and water-insoluble, allowing for EC-ethanol to be injected as a liquid and precipitate into a solid, occluding the leakage of ethanol upon contact with tissue. The aims of this study were to compare the 1) safety, 2) release kinetics, 3) spatial distribution, 4) necrotic volume, and 5) overall survival of EC-ethanol to conventional ethanol ablation in a murine breast tumor model. Non-target tissue damage was monitored through localized adverse events recording, ethanol release kinetics with Raman spectroscopy, injectate distribution with in vivo imaging, target-tissue necrosis with NADH-diaphorase staining, and overall survival by proxy of tumor growth. EC-ethanol exhibited decreased localized adverse events, a slowing of the release rate of ethanol, more compact injection zones, 5-fold increase in target-tissue necrosis, and longer overall survival rates compared to the same volume of pure ethanol. A single 150 μL dose of 6% EC-ethanol achieved a similar survival probability rates to six daily 50 μL doses of pure ethanol used to simulate a slow-release of ethanol over 6 days. Taken together, these results demonstrate that EC-ethanol is safer and more effective than ethanol alone for ablating tumors