Metabolic acidosis is a severe complication of chronic kidney disease (CKD) which is associated with nefarious impairments such as bone demineralization, muscle wasting, and hormonal alterations, for example, insulin resistance. Whilst it is possible to control this condition with alkali treatment, consisting in the oral administration of sodium citrate or sodium bicarbonate, this type of intervention is not free from side effects. On the contrary, opting for the implementation of a targeted dietetic-nutritional treatment for the control of CKD metabolic acidosis also comes with a range of additional benefits such as lipid profile control, increased vitamins, and antioxidants intake. In our review, we evaluated the main dietary-nutritional regimens useful to counteract metabolic acidosis, such as the Mediterranean diet, the alkaline diet, the low-protein diet, and the vegan low-protein diet, analyzing the potentialities and limits of every dietary-nutritional treatment. Literature data suggest that the Mediterranean and alkaline diets represent a valid nutritional approach in the prevention and correction of metabolic acidosis in CKD early stages, while the low-protein diet and the vegan low-protein diet are more effective in CKD advanced stages. In conclusion, we propose that tailored nutritional approaches should represent a valid therapeutic alternative to counteract metabolic acidosis.
Diabetes mellitus (DM) is a glucose metabolism disorder characterized by chronic hyperglycemia resulting from a deficit of insulin production and/or action. DM affects more than 1 in 10 adults, and it is associated with an increased risk of cardiovascular morbidity and mortality. Cardiovascular disease (CVD) accounts for two thirds of the overall deaths in diabetic patients, with coronary artery disease (CAD) and ischemic cardiomyopathy as the main contributors. Hyperglycemic damage on vascular endothelial cells leading to endothelial dysfunction represents the main initiating factor in the pathogenesis of diabetic vascular complications; however, the underlying pathophysiological mechanisms are still not entirely understood. This review addresses the current knowledge on the pathophysiological links between DM and CAD with a focus on the role of epigenetic modifications, including DNA methylation, histone modifications and noncoding RNA control. Increased knowledge of epigenetic mechanisms has contributed to the development of new pharmacological treatments (“epidrugs”) with epigenetic targets, although these approaches present several challenges. Specific epigenetic biomarkers may also be used to predict or detect the development and progression of diabetes complications. Further studies on diabetes and CAD epigenetics are needed in order to identify possible new therapeutic targets and advance personalized medicine with the prediction of individual drug responses and minimization of adverse effects.
Primary prevention is crucial for coronary heart disease (CAD) and the identification of new reliable biomarkers might help risk stratification or predict adverse coronary events. Alternative splicing (AS) is a less investigated genetic factors implicated in CAD etiology. We performed an RNA-seq study on PBMCs from CAD patients and control subjects (CTR) and observed 113 differentially regulated AS events (24 up and 89 downregulated) in 86 genes. The RECK (Reversion-inducing-cysteine-rich protein with Kazal motifs) gene was further analyzed in a larger case study (24 CTR subjects, 72 CAD and 32 AMI patients) for its Splicing-Index FC (FC = −2.64; p = 0.0217), the AS event involving an exon (exon 18), and its role in vascular inflammation and remodeling. We observed a significant downregulation of Long RECK splice variant (containing exon 18) in PBMCs of AMI compared to CTR subjects (FC = −3.3; p < 0.005). Interestingly, the Short RECK splice variant (lacking exon 18) was under-expressed in AMI compared to both CTR (FC = −4.5; p < 0.0001) and CAD patients (FC = −4.2; p < 0.0001). A ROC curve, constructed combining Long and Short RECK expression data, shows an AUC = 0.81 (p < 0.001) to distinguish AMI from stable CAD patients. A significant negative correlation between Long RECK and triglycerides in CTR group and a positive correlation in the AMI group was found. The combined evaluation of Long and Short RECK expression levels is a potential genomic biomarker for the discrimination of AMI from CAD patients. Our results underline the relevance of deeper studies on the expression of these two splice variants to elucidate their functional role in CAD development and progression.
Chronic kidney disease (CKD) represents a public health problem because it is characterized by several comorbidities, including uremic sarcopenia (US), and a poor quality of life. Currently, there are no standardized treatments available to counteract the onset of US but only some possible therapeutic approaches to slow its progression. The aim of this pilot study is to collect descriptive data in order to design a clinical trial based on the power analysis and simple size. The purpose of this pilot study was to evaluate the possible beneficial action induced by the functional anti-inflammatory and antioxidant bars in combination with the adapted physical activity (APA), on the onset and progression of US and other related-CKD comorbidities. We enrolled 21 CKD patients under conservative therapy, divided into four groups: (A) the physical exercise program (PEP), three times a week, in combination with the daily consumption of the two functional bars group; (B) the PEP group; (C) the daily consumption of the two functional bars group; (D) the control group. The duration of the study protocol was 12 weeks. We observed an improvement trend of body composition, blood pressure levels, lipid metabolism, and functional test in A and B groups. These preliminary data would seem to confirm the effectiveness of APA and to demonstrate the additive role of the natural bioactive compound’s assumption in countering US and other CKD comorbidities.
Among the chronic non-communicable degenerative diseases (CDNCDs), chronic kidney disease (CKD) represents a global public health problem. Recent studies demonstrate a mutual cause–effect relationship between CKD and oral diseases, in which the presence of one induces the onset and faster progression of the other. In particular, the oral cavity alterations more frequent in CKD patients are: chronic periodontitis diseases, bone lesions, oral infections, and oral cancer lesions. Currently, a standardized therapy for the treatment of oral diseases is lacking. For this reason, natural bioactive compounds (NBCs), characterized by several health effects, such as antioxidant, antimicrobial, anti-inflammatory and anti-cancer actions, represent a new possible adjuvant therapy in the management of these pathological conditions. Among NBCs, polyphenols play a leading role due to positive modulation of oral microbiota, preventing and correcting oral dysbiosis. Moreover, these compounds exert anti-inflammatory effects, such as inhibiting the production of pro-inflammatory cytokines and the expression of cycloxigenase-2. In this light, the formulation of a new mouthwash/gel/gingival paste, with a high content of polyphenols in association with NBCs characterized by antimicrobial action, could represent a future therapy of oral disease in CKD patients.
Several studies highlighted a correlation between exhaled air volatile organic compounds (VOCs) and some pathological conditions, such as chronic kidney disease (CKD), chronic liver disease, etc. In fact, in literature has been reported that CKD is characterized by an increased concentration of ammonia, trimethylamine (TMA) and isoprene compared to healthy subjects. Currently, there is not a validate and standardized method to detect VOCs. For this purpose, we examined the utility of selected ion flow tube-mass spectrometry (SIFT-MS) to measure VOCs in CKD patients and we evaluated the possible correlation between VOCs and the presence of CKD and its stage. We enrolled 68 CKD patients under conservative therapy and 54 healthy subjects. The analysis of the VOCs of the exhaled air of the enrolled subjects was performed by SIFT-MS. Among all the VOCs analyzed, the most relevant results by ROC curves were observed for TMA, acetone, ammonia and dimethyl sulfide. We found that a breath TMA concentration superior to 26 ppbv characterizes a 6.11 times greater risk of CKD, compared to subjects with lower levels. Moreover, we detected an increased concentration of acetone and ammonia in CKD patients compared to healthy subjects. We highlight the potential utility of SIFT-MS in CKD clinical management.Clinical trial registry: R.S. 15.19 of 6 February 2019.
Coronary artery anomalies and variants are relatively uncommon congenital disorders of the coronary artery anatomy and constitute the second most common cause of sudden cardiac death in young competitive athletes. Normally there are two main coronary arteries, which stem from the sinuses of Valsalva and descend towards the cardiac apex. The most frequent anomalous origin of the coronary arteries associated with sudden cardiac death is the anomalous origin of a coronary artery from the contralateral sinus, particularly if the anomalous coronary artery has a course between the aorta and the pulmonary artery. The diagnosis of a coronary artery anomaly is insidious since patients are usually asymptomatic. Indeed, in most of the cases, coronary anomalies are discovered incidentally during coronary angiography or on autopsy following sudden cardiac death. However, in some cases, symptoms like angina, syncope, heart failure, and myocardial infarction may occur. We want to describe the case of a 54 years old man who went to another hospital of our district with chest pain. The EKG showed an infero-lateral STEMI. The patient underwent systemic thrombolysis complicated by arrhythmic storm, treated with effective DC shock, then he was urgently transferred to our Hospital to perform a PCI rescue. The coronary angiography showed a critical stenosis of the right coronary artery, treated with the implantation of a zotarolimus-eluting coronary stent system. Surprisingly, an abnormal origin of the anterior interventricular artery and circumflex artery from seperated hosts in the right coronary sinus was detected. A computed tomography showed the separated origin of the right coronary artery and the left main from the right coronary sinus; moreover, the left main presented a retroaortic course between the bulb and the left atrium; the left anterior intraventricular artery run anterior to the aortic root. During hospitalization, a diagnosis of diabetes was made with consequent setting of adequate hypoglycemic therapy. Serial echocardiograms showed an improval in the ejection fraction (from 35–40% to 50%). The patient was discharged in well clinical conditions and 1 month later at the follow-up, during an outpatient visit, he was fully asymptomatic. The dynamic EKG according to Holter showed rare isolated ventricular beats; laboratory tests were normal. The anomalous origin of a coronary ostium from the contralateral sinus is the most frequently anomaly which is associated with sudden cardiac death, in particular when the left coronary artery origins from the right sinus. The rapid advancement of the imaging techniques, including CT, CMR, intravascular ultrasound, and optical coherence tomography, have provided us with a wealth of new information on this subject. Coronary artery CT offers the best performance in terms of spatial resolution, acquisition time, and image contrast but the use is limited due the dose of ionizing radiation and the use of contrast agents, in particular taking into account that most patients are young. CMR is capable of visualizing the origin of the coronary arteries non-invasively, without use of ionizing radiation and contrast agents. Currently however, due to spatial resolution, the capability of CMR to visualize smaller coronary branches is still a limiting factor preventing full assessment of coronary arteries using this modality. Developments and more widespread access to advanced cardiac imaging will undoubtedly lead to earlier diagnoses. The taxonomies of the anomalous origin of coronary arteries are inconsistent and complex and so we want to make our contribution to the register of cases of abnormal origin of coronary arteries for the risk of sudden cardiac death and ischaemic events related to.
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