Vitamin D has important anti-inflammatory, anti-microbial properties and plays a central role in host immune response. Due to the crucial role of the kidneys in the metabolism of vitamin D, patients with chronic kidney disease (CKD), are prone to vitamin D deficiency. The resultant reduction in the production of calcitriol, the activated form of vitamin D in patients with CKD is responsible for exacerbating the existing renal impairment and periodontal inflammation. Recent evidence suggests a bidirectional, causal relationship between periodontitis and renal functional status. Both conditions have shared pathophysiologic mechanisms including oxidative stress, increases in the systemic inflammatory burden and impaired host response. This review explores the association between vitamin D, CKD and periodontitis. The review summarises the current evidence base for the classical and non-classical vitamin D metabolic pathways, the biological mechanisms linking vitamin D deficiency, CKD and periodontitis, as well as the bidirectional relationship between the two chronic inflammatory conditions. Finally, the paper explores the impact of vitamin D deficiency on CKD, periodontitis, and related co-morbidities.

Vitamin D (VD) is a pro-hormone essential for life in higher animals. It is present in few types of foods and is produced endogenously in the skin by a photochemical reaction. The final step of VD activation occurs in the kidneys involving a second hydroxylation reaction to generate the biologically active metabolite 1,25(OH)₂-VD. Extrarenal 1α-hydroxylation has also been described to have an important role in autocrine and paracrine signaling. Vitamin D deficiency (VDD) has been in the spotlight as a major public health-care issue with an estimated prevalence of more than a billion people worldwide. Among individuals with chronic kidney disease (CKD), VDD prevalence has been reported to be as high as 80%. Classically VD plays a pivotal role in calcium and phosphorus homeostasis. Nevertheless, there is a growing body of evidence supporting the importance of VD in many vital nonskeletal biological processes such as endothelial function, renin-angiotensin-aldosterone system modulation, redox balance and innate and adaptive immunity. In individuals with CKD, VDD has been associated with albuminuria, faster progression of kidney disease and increased all-cause mortality. Recent guidelines support VD supplementation in CKD based on extrapolation from cohorts conducted in the general population. In this review, we discuss new insights on the multifactorial pathophysiology of VDD in CKD as well as how it may negatively modulate different organs and systems. We also critically review the latest evidence and controversies of VD monitoring and supplementation in CKD patients.

Chronic kidney disease (CKD) is a major non-communicable disease associated with high rates of premature morbidity and mortality. The prevalence of hypovitaminosis D (deficiency of 25(OH)D or 25D) is greater in racial/ethnic minorities and in patients with CKD than the general population. Low 25D is associated with bone and mineral disorders as well as immune, cardiometabolic and cardiovascular (CV) diseases. Thus, it has been suggested low 25D contributes to the poor outcomes in patients with CKD. The prevalence of hypovitaminosis D rises progressively with advancing severity of kidney disease with over 30% of patients with CKD stage 3 and 70% patients with CKD stage 5 estimated to have low levels of 25D. This report describes several of the abnormal physiologic and counter-regulatory actions related to low 25D in CKD such as those in oxidative stress and inflammatory systems, and some of the preclinical and clinical evidence or lack of thereof of normalizing serum 25D levels to improve outcomes in patients with CKD, and especially for the high risk subset of racial/ethnic minorities who suffer from higher rates of advanced CKD and hypovitaminosis D.

Cadmium (Cd) is a metal with no nutritional or physiological value, but is found in most people because it is a contaminant in nearly all food types. The intestinal absorption rate determines the body burden of Cd because humans lack a physiologic mechanism for excretion of the metal. Most acquired Cd accumulates in the kidneys, in which the Cd content increases through age 50 but falls thereafter. The decline from maximal kidney content is probably due to release of Cd from injured tubular cells into urine and replacement of destroyed nephrons by scar tissue. Chronic kidney disease is diagnosed when the estimated glomerular filtration rate (eGFR) falls below 60 mL/min/1.73 m2, or when albuminuria is present. Albuminuria is defined as an albumin-to-creatinine ratio ≥ 30 mg/g creatinine in women or ≥ 20 mg/g creatinine in men that persists for at least 3 months. Generally, Cd-induced reductions in eGFR are not reversible, and Cd nephropathy may progress to end-stage kidney disease. There is no evidence that elimination of current environmental exposure can reverse Cd nephropathy, and no theoretical reason to believe that such a reversal is possible. This review provides an update of knowledge concerning CKD in population environmentally exposed to Cd. Special attention is devoted to mechanisms of Cd-induced albuminuria concurrently with eGFR reductions, and the difficult challenge of exposure guidelines sufficient to eliminate the risk of Cd-induced CKD is addressed.

Chronic kidney disease (CKD) and cardiovascular disease (CVD) are highly prevalent conditions, each significantly contributing to the global burden of morbidity and mortality. CVD and CKD share a great number of common risk factor, such as hypertension, diabetes, obesity, and smoking among others. Their relationship extends beyond these factors, encompassing intricate interplay between the two systems. Within this complex network of pathophysiological processes, vitamin D has emerged as a potential linchpin, exerting influence over diverse physiological pathways implicated in both CKD and CVD. In recent years, scientific exploration has unveiled a close connection between these two prevalent conditions and vitamin D, a crucial hormone traditionally recognized for its role in bone health. This article aims to provide an extensive review of vitamin D's multifaceted and expanding actions concerning its involvement in CKD and CVD.

The association between angiotensin-converting enzyme insertion/deletion (ACE I/D) polymorphisms and plasma ACE levels may allow for the optimization of a preventive intervention to reduce cardiovascular morbidity and mortality in the chronic kidney disease (CKD) population. In this study, we aimed to analyze the association between ACE I/D polymorphism and cardiovascular mortality risk among non-hemodialyzed chronic kidney disease patients. This cross-sectional study examined 70 patients of Javanese ethnic origin with stable CKD who did not receive hemodialysis. ACE I/D polymorphisms, plasma ACE levels, atherosclerotic cardiovascular disease (ASCVD) risk, and cardiovascular mortality risk were investigated. As per our findings, the I allele was found to be more frequent (78.6) than the D allele (21.4), and the DD genotype was less frequent than the II genotype (4.3 vs. 61.4). The ACE I/D polymorphism had a significant direct positive effect on plasma ACE levels (path coefficient = 0.302, p = 0.021). Similarly, plasma ACE levels had a direct and significant positive effect on the risk of atherosclerotic cardiovascular disease (path coefficient = 0.410, p = 0.000). Moreover, atherosclerotic cardiovascular disease risk had a significant positive effect on cardiovascular mortality risk (path coefficient = 0.918, p = 0.000). The ACE I/D polymorphism had no direct effect on ASCVD and cardiovascular mortality risk. However, our findings show that the indirect effects of high plasma ACE levels may be a factor in the increased risk of ASCVD and cardiovascular mortality in Javanese CKD patients.

This article provides a thorough overview of biomarkers, pathophysiology, and molecular pathways involved in the transition from acute kidney injury (AKI), acute kidney disease (AKD) to chronic kidney disease (CKD). It categorizes the biomarkers of AKI into stress, damage, and functional markers, highlighting their importance in early detection, prognosis, and clinical application. The pathophysiological mechanisms underlying AKI, AKD, including renal hypoperfusion, sepsis, nephrotoxicity, and immune responses, with the impact on renal injury. In addition, various molecules play pivotal roles in inflammation and hypoxia, triggering maladaptive repair, mitochondrial dysfunction, immune system reactions, and cellular senescence of renal cell. Key signaling pathways, such as Wnt/β-Catenin, TGF-β/SMAD, and Hippo/YAP/TAZ, promote fibrosis and impact renal function. The Renin-Angiotensin-Aldosterone System (RAAS) triggers a cascade leading to renal fibrosis, with aldosterone exacerbating oxidative stress and cellular changes that promote fibrosis. Clinical evidence suggests RAS inhibitors may protect against CKD progression, especially post-AKI, though more extensive trials are needed to confirm their full impact.

Statistical data extracted from national databases demonstrate a continuous growth in the incidence and prevalence of chronic kidney disease (CKD) and the ineffectiveness of current policies and strategies based on individual risk factors to reduce them, as well as their mortality and costs. Some innovative programs, telemedicine and government interest in the prevention of CKD, did not facilitate timely access to care, continuing the increased demand for dialysis and transplants, high morbidity and long-term disability. In contrast, new forms of kidney disease of unknown etiology affected populations in developing countries and underrepresented minorities, who face socioeconomic and cultural disadvantages. With this background, we analyze in the existing literature the effects of social determinants in CKD, concluding that it is necessary to strengthen current kidney health strategies, designing in a transdisciplinary way, a model that considers demographic characteristics integrated into individual risk factors and risk factors population, incorporating the population health perspective in public health policies to improve results in kidney health care, since CKD continues to be an important and growing contributor to chronic diseases.

Vascular calcification (VC), is a common complication in patients with chronic kidney disease and increases mortality. Although oxidative stress is involved in the onset and progression of this disorder, the specific role of some main redox regulators such as catalase, the main scavenger of H2O2, remains unclear. In the present study, epigastric arteries of kidney transplant recipients, an in vivo model of VC and an in vitro model of VC exhibiting catalase overexpression (Cts) were analyzed. Peri-calcification areas of human epigastric arteries have increased levels of catalase and cytoplasmic rather than nuclear RUNX2. In the in vivo model, advanced aortic VC concurs with lower levels of the H2O2 scavenger, glutathione peroxidase 3 compared to controls. In an early model of calcification using vascular smooth muscle cells (VSMCs), Cts VSMCs showed the expected increase in RUNX2 total levels. However, Cts VMSC also exhibited lower percentage of the nucleus stained for RUNX2 in response to calcifying media. At this early model of VC we did not observe dysregulation of mitochondrial redox state, an increase in general redox state was observed in the cytoplasm. These in vivo and in vitro results highlight the complex role of antioxidant enzymes as catalase in the process of VC by regulation of RUNX2 location.

The different cell subsets of the immune system express vitamin D receptor (VDR). Through VDR, vitamin D exerts different functions which influences on immune responses, as previously shown in different preclinical models. Based on this background, retrospective studies have explored the impact of vitamin D levels on the outcome of patients undergoing allogeneic hematopoietic stem cell transplantation, showing that vitamin D deficiency is related to an increased risk of complications, especially graft-versus-host disease. These results have been confirmed in a prospective cohorts trial, although further studies are required to confirm this data. In addition, the role of vitamin D on the treatment of hematologic malignancies has also been explored. Considering this dual effect both on the immune system as well as on tumor cells in patients with hematologic malignancies, vitamin D might be useful in this setting both to decrease graft-versus-host disease and relapse rates.

Beyond plasma glucose-lowering in patients with type 2 diabetes, sodium- glucose cotransporter 2 inhibitors (SGLT2i) significantly reduced the hospitalization for heart failure (HF) and retarded the progression of chronic kidney disease (CKD). Endothelial dysfunction is not only involved in the development and progression of cardiovascular disease (CVD), and is also associated with the progression of CKD. In patients with type 2 diabetes, hyperglycemia, insulin resistance, hyperinsulinemia and dyslipidemia induce the development of endothelial dysfunction. SGLT2i have shown an improvement in endothelial dysfunction, as assessed by flow-mediated vasodila-tion, in individuals at high risk for CVD. Along with an improvement of endothelial dysfunction, SGLT2i showed improvements in oxidative stress, inflammation, mitochondrial dysfunction, glucotoxicity such as advanced glycation end products signaling and nitric oxide bioavailability. The improvements in endothelial dysfunc-tion and such endothelium-derived factors may play an important role in preventing the development of coronary artery disease, coronary microvascular dysfunction and diabetic cardiomyopathy which cause HF and in retarding CKD. The suppression of the development of HF and the progression of CKD achieved by SGLT2i might have been largely induced by the improvement of vascular endothelial function by SGLT2i.

Background: Acute kidney disease (AKD) is a known risk factor for increased mortality and evolution towards chronic kidney disease (CKD) in adults. The data regarding children are scarce. The purpose of our study is to explore the risk factor for AKD and impact of AKD following an acute kidney injury (AKI) episode in children on mortality and new-onset CKD. Methods: We retrospectively evaluated 736 children with ages between 2 and 18 years old with AKI admitted in a tertiary care hospital from the west Romania over a 9 years period. Results: AKD incidence following AKI was 17%. Patients that developed AKD were older, with higher baseline serum creatinine values, urea, C reactive protein and lower proteins, haemoglobin and sodium. They were more often exposed to sepsis, critical illness and nephrotoxic medications and presented certain susceptibilities like CKD, neoplasia, anemia, heart failure, arterial hypertension, stem cell transplant and female gender. AKI causes that increased the risk of AKD were intrinsic ones. AKD increased the overall mortality by three times. The factors that independently increased the risk of evolution towards CKD were AKD, acute tubular necrosis and higher baseline serum creatinine values. Conclusions: AKD is an independent risk factor for mortality and new-onset CKD in children.

Background: Overall survival is the most important outcome for treatment response in feline chronic kidney disease (CKD). Beraprost has been shown to reduce the kidney function decline in cats with International Renal Interest Society (IRIS) stage 2 and 3 CKD. However, association with prolonged survival has not yet been examined. Objective: To assess the relationship between beraprost and overall survival in cats with CKD in real clinical practice. Animals: Client-owned cats with IRIS stage 3 CKD (n = 134), evaluated between 2017 and 2020. Methods: Retrospective cohort study based on data from electronic medical records of one hospital. Results: Multivariable Cox regression models on all treatment effects showed that beraprost only was related to better survival (P = 0.028). The cohort was divided into “beraprost therapy” and “no beraprost therapy” groups, and survival analyses revealed that overall survival was significantly longer in the beraprost therapy group, using Kaplan-Meier curves (P = 0.004). However, baseline phosphate is known to be an important prognostic indicator and was not well balanced between the two groups. Therefore, a subcohort of 97 cats was selected (those having baseline phosphate < 6.0 mg/dL) that allowed for this parameter to be balanced between groups. The survival data in this subcohort was consistent with that of the overall study cohort. Conclusions: In feline patients with CKD, beraprost therapy was associated with better overall survival.

Diabetes mellitus (DM) and chronic kidney disease (CKD) are common in middle aged and elderly individuals. DM may accelerate the aging process, and the age-related declines in the estimated Glomerular Filtration Rate (eGFR), can pose a challenge to diagnose diabetic kidney disease (DKD) using standard diagnostic criteria especially with absence of severe albuminuria among the elderly. In the presence of CKD and DM, elderly patients may need multidisciplinary care due to susceptibility to various health issues e.g., cognitive decline, auditory or visual impairment, various comorbidities, complex medical regimens, and increased sensitivity to medication adverse effects. As a result, it can be challenging to apply recent therapeutic advancements for the general population to the elderly. We review the evidence that the benefits from these newer therapies apply equally to elderly and non-elderly patients and propose a framework for the management of DKD by discussing the nonpharmacological measures and pharmacological management with renin angiotensin system inhibitors (RASi), Sodium Glucose Co-Transporter two inhibitors (SGLT2i), non-steroidal mineralocorticoids receptor antagonists (MRAs), and Glucagon Like Peptide 1 Receptor Agonists (GLP1-RAs).

Hepatitis C virus (HCV) is a major public health threat associated with serious clinical consequences worldwide. The WHO reports an estimated 58 million people globally living with chronic hepatitis C virus (HCV) infection, with 1.5 million new cases and over 350,000 deaths annually due to HCV-related diseases. Despite the existence of multiple diagnostic methods, the accessibility of diagnosis and treatment is often hindered across the continent by limited resources, insufficient healthcare infrastructure, and low public awareness of Hepatitis C virus Hepatitis C virus infection is a major public health concern in African countries, which have the highest prevalence rates of HCV in the world (1–26%). Egypt, African country which had the highest prevalence of Hepatitis C virus infection in the world. Its national hepatitis C elimination initiative emerges as an exemplary case of success an having screened over 60 million individuals, and treated more than 4 million, thereby markedly diminishing both the prevalence and incidence of the disease. The strategies employed by Egypt offer critical insights and adaptable frameworks for other African Countries facing analogous challenges. The Aim of this Review is to highlight the triumphs and hurdles of Egypt's approach, while also providing strategic guidance for African Countries to accelerate the journey towards the eradication of hepatitis C.

Background: Cell-free plasma DNA (cfDNA) is composed of circulating extracellular DNA originating from apoptosis or cell necrosis. It is generally present in healthy individuals, but its levels increase in different clinical conditions, such as kidney disease, sepsis, myocardial infarction, trauma and cancer. Caspase-3 plays a central role in apoptosis, a mechanism of programmed cell death involved in the pathogenesis of chronic kidney disease (CKD). Methods: We compared cfDNA and caspase-3 levels in 25 CKD patients and in 10 healthy subjects, evaluating the modification of their concentrations according to CKD stage. We also analyzed the correlation between cfDNA and caspase-3 levels in CKD patients and the correlation between cfDNA and caspase-3 levels and creatinine and urea. Results: CfDNA and caspase-3 levels were higher in CKD patients compared to healthy subjects, in particular in patients with advanced renal disease. A positive correlation between cfDNA and caspase-3 levels and between cfDNA and caspase-3 and creatinine and urea was also observed. Conclusion: Patients with chronic kidney disease present higher levels of cfDNA and caspase-3 levels compared with healthy subjects. The worsening of renal damage and the increase in uremic toxin concentration are associated to higher levels of cfDNA and caspase-3 levels, thus reflecting a central role of apoptosis in the pathogenesis of CKD.

Renal uric acid (UA) reabsorption is mainly mediated by urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9). Dotinurad selectively inhibits URAT1 and do not inhibit other UA transporters such as GLUT9, ATP-binding cassette transporter G2 (ABCG2) and organic anion transporter1/3 (OAT1/3). We discovered that dotinurad improved metabolic parameters and renal function in hyperuricemic patients. We consider a significance of high selectivity in inhibiting URAT1 by dotinurad for metabolic syndrome, chronic kidney disease (CKD), and cardiovascular disease (CVD). Dotinurad inhibits selectively URAT1 and increases UA in the proximal tubules, and UA may compete with glucose for GLUT9, reducing glucose reabsorption. The inhibition of UA entry via URAT1 to liver and adipose tissues by dotinurad increased energy expenditure and decrease lipid synthesis and inflammation in rats. The inhibition of URAT1 in kidney, liver and adipose tissues improve metabolic parameters. CKD patients accumulate uremic toxins such as indoxyl sulfate (IS) in the body. ABCG2 regulates renal and intestinal excretion of IS which strongly affects CKD. OAT1/3 inhibitors suppress IS uptake into kidney, increasing plasma IS, which produces oxidative stress, inducing vascular endothelial dysfunction in CKD patients. The high-selective inhibition of URAT1 by dotinurad may be beneficial for metabolic syndrome, CKD and CVD.

Chronic Kidney Disease is a medical condition that causes the decrease in the kidney function and can eventually derive in a total cessation of the work of the organ. It currently affects >10% of the global population, and the number is expected to grow within the next few years, since the correlated diabetes condition is escalating too. Diagnosing the disease on its early stages is crucial to improve life quality, and to increase the chances of survival. The traditional diagnostic methods, which include a biopsy, are invasive, expensive and dangerous. With the use of machine learning algorithms like neural networks, random forest and genetic algorithms, this paper seeks to discover an algorithm with high accuracy, whose selected attributes will be the most optimal combination aiming to reduce the cost, level of invasiveness, and easiness to obtain.

Intense alterations of mineral and bone metabolism are prevalent in chronic kidney disease (CKD) and represent an important cause of morbidity and decreased quality of life. These disor-ders have traditionally been defined as renal osteodystrophy and classified based on bone biop-sy, but due to a lack of bone biopsy data and validated radiological methods to evaluate bone morphology in children, it has been difficult to adequately evaluate renal osteodystrophy in pe-diatric CKD. This has led to suboptimal management of bone disorders in children. CKD-mineral and bone disorder (CKD-MBD) is a new term used to describe a systemic disorder of mineral and bone metabolism as a result of CKD. CKD-MBD is a triad of biochemical imbalances of cal-cium, phosphate, parathyroid hormone and vitamin D, bone abnormalities and soft tissue calci-fication. This literature review aims to explore the pathogenesis, diagnostic approach, and treat-ment of CKD-MBD in children and the specific consequences of renal osteodystrophy on growing skeleton, with a specific focus on the biological basis of this peculiar condition.

Hashimoto's thyroiditis (HT) is essentially featured by self-tissue destruction by means of the adaptive immune responses that evade immune regulation. Vitamin D carries out an immunomodulatory role that appears to promote immune tolerance. The aim of this study is to elaborate a narrative review about the relationship between vitamin D status and HT and the role of vitamin D supplementation to reduce HT risk by modulating the immune system. There is an extensive literature confirming that vitamin D levels are significantly lower in HT patients compared to healthy people. On the other hand, after the supplementation with cholecalciferol in patients with HT and vitamin D deficiency, thyroid autoantibody titer decreased significantly, However, there are no conclusive results on the effect of vitamin D supplementation on the thyroid function. The confirmation of the beneficial effects of vitamin D in the prevention and treatment of autoimmune thyroid diseases require additional randomized, double-blind, placebo-controlled trials with longer follow-up.

Vitamin D is a nutrient with anti-inflammatory properties whose role is currently being evaluated in COVID-19. Although studies are conflicting, they seem to suggest a role for vitamin D in reducing disease susceptibility but not in improving clinical outcome. In order to understand why vitamin D does not seem to have much effect on decreasing disease severity, it is essential to appreciate pulmonary vitamin D metabolism. To reach the pulmonary compartment, vascular endothelial cells would need to take up vitamin D from the blood stream, but they lack vitamin D receptor (VDR) and the activating enzyme CYP27B1. Endothelialitis – an important disease manifestation of COVID-19 – is therefore not expected to be directly affected by vitamin D. Bronchial epithelial cells are usually among the first to be infected with SARS-CoV-2. They do express both VDR and CYP27B1, but circulating vitamin D may not reach bronchial epithelial cells without transportation from the blood stream through the blood vessel wall. Inhalation therapy with vitamin D has therefore been suggested as an alternative for oral administration to bypass endothelial cells and efficaciously target bronchial epithelium. In conclusion, based on the principles of pulmonary vitamin D metabolism, it is not expected that vitamin D administration has a significant effect on COVID-19 severity. Vitamin D is more likely to reduce SARS-CoV-2 susceptibility, but reaching the airways with oral supplementation will be difficult and vitamin D inhalation therapy should be considered.

Patients with chronic kidney disease (CKD), particularly those with end-stage kidney disease (ESKD) undergoing dialysis or kidney transplantation, face ongoing challenges in relation to the risk of COVID-19. In addition to their underlying condition, factors such as immune-evasive variants, immunosuppressive therapies, and the need for dialysis contribute to poor COVID-19 outcomes in this population. Severe COVID-19 can lead to the deterioration of CKD/ESKD, resulting in acute kidney injury, septic shock, and respiratory failure. Moreover, patients with CKD/ESKD have shown impaired response to COVID-19 vaccination, with seroconversion failures associated with the burden of immunosuppressive treatments, further heightening their vulnerability to severe disease. Despite the current endemic, it is crucial to acknowledge the ongoing significance of COVID-19 as a serious threat to patients burdened with chronic diseases like CKD and ESRD. Understanding the impact of COVID-19 on these patients is essential, as they remain at risk of severe disease progression. This paper presents the results of a literature review to enhance our understanding of COVID-19-related risks in patients with CKD/ESKD. Expert insights and illustrative scenarios provide practical perspectives and highlight the importance of risk stratification based on clinical factors for guiding targeted measures and treatments to mitigate COVID-19 risks in these vulnerable patients.

CKD in HF patients is very common condition, their dysfunction is closely linked and influence each other, so their management required multidisciplinary and personalized approaches. The diagnosis of HF and CDK relies on signs and symptoms. Several tools, such as blood-based biomarkers and echography help us to clarify and discriminate the main characteristics of these patients. Evidence in improving survival due to new drug-employment in HF, has increasingly challenged physicians to manage patients with multiple diseases, especially in patients with CKD. The difficulty is in the safe administration of these drugs in patients with HF and CKD. Knowing up to which values ​​of creatinine or renal clearance any drug can be administered is fundamental. We wanted to summarize, on this sizable and complex topic, the experiences of various prior study to get clearer ideas and a more precise reference about the assessment and management of HF and CKD.

OPMDs (Oral Potentially Malignant Disorders) are a group of disorders affecting the oral mucosa that are characterized by aberrant cell proliferation and a higher risk of malignant transformation. Vitamin D (VitD) and its receptor (VDR) have been extensively studied for their potential contributions to the prevention and therapeutic management of a range of diseases and neoplastic conditions, including oral cancer. Observational studies suggest correlations between VitD deficiency and higher cancer risk, worse prognosis, and increased mortality rates. Interestingly, emerging data also reveals a link between VitD insufficiency and the onset or progression of OPMDs. Understanding the role of the VitD-VDR axis not only in established oral tumors but also in OPMDs might thus enable early detection and prevention of malignant transformation. With this article, we want to provide an overview of current knowledge about OPMDs and VitD, and investigate their potential association and ramifications for clinical management of OPMDs.

Background: Studies have demonstrated the link between vitamin D-related genetic variations and non-skeletal outcomes. We aimed to identify all available data on the association of vitamin D-related genetic variations with non-alcoholic fatty liver disease (NAFLD). Methods: Potentially eligible studies were identified from Embase and Medline databases from inception to June 2022 using search strategy that comprised terms for “Vitamin D” and “NAFLD”. Eligible study must report the association between vitamin D-related genetic variations and presence, severity or response to treatment of NAFLD. Data were extracted from each eligible study. Results: A total of 3,495 articles were identified. After systematic review, twelve studies were in-cluded. A total of 26 genetic variations were identified. Presence of NAFLD was associated with variations of GC (rs222054, rs222020, rs10011000, rs7041), VDR (rs2228570, rs11168287, rs10783219, rs4752), CYP24A1 (rs3787557, rs6068816, rs2296241, rs2248359) and CYP27B1 (rs4646536). Severity of NAFLD was associated with variations of GC (rs4588), VDR (rs2228570, rs4334089), CYP2R1 (rs10741657), DHCR7 (rs1544410, rs3829251, rs12785878) and CYP24A1 (rs3787557, rs6068816, rs6097809, rs6127119, rs2248359, rs3787554, rs4809960, rs6022999). Response to calcitriol treatment was associated with variation of VDR (rs10735810). Conclusions: Multiple vitamin D-related genetic variations were associated with NAFLD, indi-cating the role of vitamin D in the pathogenesis of NAFLD.

Osteitis fibrosa cystica (OFC) and Brown Tumour are two related but distinct types of bone lesions that result from overactivity of osteoclasts most often associated with chronic kidney disease (CKD). Despite their potential consequences, these conditions are poorly understood because of their rare prevalence and variability in their clinical manifestation. Canonically, OFC and Brown Tumours are caused by secondary hyperparathyroidism in CKD. Recent literature showed that multiple factors such as hyperactivation of the renin-angiotensin-aldosterone system and chronic inflammation may also contribute to the occurrence of these diseases through osteoclast activation. Moreover, hotspot KRAS mutations were identified in these lesions placing them in the spectrum of RAS-MAPK-driven neoplasms, while until recently thought to be reactive lesions. Some risk factors contributed to the occurrence of OFC and Brown Tumour such as age, gender, comorbidities, and certain medications. The diagnosis of OFC and Brown Tumour includes clinical symptoms involving chronic bone pain and laboratory finding of hyperparathyroidism. In radiological imaging, the X-ray and Computed tomography (CT) scan could show lytic or multi-lobular cystic alterations. Histologically both lesions are characterized by clustered osteoclast in a fibrotic hemorrhagic background. Based on the latest understanding of the mechanism of OFC, this review elaborates on the manifestation, diagnosis, and available therapies that can be leveraged to prevent the occurrence of OFC and Brown Tumour.

Cardiovascular diseases (CVDs) and chronic kidney disease (CKD) are frequently interconnected and their association leads to an exponential increase in the risk of both fatal and non-fatal events. In addition, the burden of arrhythmias in CKD patients is increased. On the other hand, the presence of CKD is an important factor that influences the decision to pursue cardiac device therapy. Data on CKD patients with device therapy is scarce and mostly derives from observational studies and case reports. Cardiac resynchronization therapy (CRT) is associated with decreased mortality, reduced heart failure symptoms and improved renal function in early stages of CKD. Implantable cardioverter defibrillators (ICDs) are associated with a significant reduction in the mortality of CKD patients only for the secondary prevention of sudden cardiac death. Cardiac resynchronization therapy defibrillator (CRT-D) is preferred in patients that meet the established criteria. The need for cardiac pacing is 3-fold higher in dialysis patients. CKD is an independent risk factor for infections associated with cardiac devices.

Chronic Kidney Disease (CKD) is a major public health concern with an increasing proportion of sufferers progressing to renal replacement therapy (RRT). Early identification of those at risk of disease progression could be key in improving outcomes. We hypothesise that urinary liver-type fatty acid binding protein (uL-FABP) may be a suitable biomarker for CKD progression and can add value to currently established biomarkers such as urinary protein to creatinine ratio (uPCR) 583 participants with CKD 1-5 (not receiving renal replacement therapy) entered a 2-yr prospective longitudinal study. UPCR and uL-FABP were measured at baseline and CKD progression was defined as either i) a decline in eGFR of >5ml/min/1.73m2 or an increase in serum creatinine by 10% at 1-yr or ii) a decline in eGFR of >6 ml/min/1.73m2, or an increase in serum creatinine by 20% at 2-yrs or iii) the initiation of RRT. A combined outcome of initiating RRT or death was also included. Approximately 40% of participants showed CKD progression. UL-FABP predicted CKD progression at both years 1 and 2 (OR 1.01, p<0.01). Sensitivity and specificity were comparable to those of uPCR (AUC 0.623 v 0.706) and heat map analysis suggested that uL-FABP in the absence of significant proteinuria can predict an increase in serum creatinine of 10% at 1yr and 20% at 2yr. The risk of the combined outcome of initiating RRT or death was 23% higher in those with high uL-FABP (p<0.01) independent of uPCR. UL-FABP appears to be a highly sensitive and specific biomarker of CKD progression. The use of this biomarker could enhance the risk stratification of CKD and its progression and should be assessed further.

Introduction: Elevated albuminuria is an important outcome of diabetic complications and metabolic syndrome (MetS), the complex metabolic abnormalities manifested as glucose intolerance, hypertension, and dyslipidemia and enlarged waist circumference. These coexisting cardio-metabolic abnormalities are also associated with oxidative stress and low grade inflammation. Vitamin C (vitC) has long been recognized as hydrophilic antioxidant and blocker of oxidative stress which also has a protective role of MetS and kidney disease. Objective: The aim of this study was to identify the predictive effect of vitC deficiency on kidney disease among patients who developed metabolic syndrome. Method and procedures: To meet this objective, the National Health and Nutrition Examination Survey (NHANES) 2007-2008 data were used. NHANES represents the civilian, non-institutionalized US population data implemented for continuous system of monitoring health, nutritional status and well-being in the US. The predictive power of MetS on AU and vitC deficiency (vitC < 0.25 mg/dl) as effect modifier was assessed with binary logistic regression. Age, gender, race and BMI were used as covariates. Results: Among the respondents, 1.9% of the US population had risk of kidney damage, whereas 14.5 % of respondents had MetS. MetS was significantly positively correlated with AU (p < 0.01). Higher elevation of albuminuria creatinine ratio (ACR) was found in participants with VCD. The regression models developed in this study showed that the severity of kidney disease measured by ACR was increased among individuals who developed both VCD and MetS compared with individuals who developed MetS only (AOR=5.53; 95% CI: 2.73, 11.21). Increasing age and being African-American in race were independently associated with elevated AU. Conclusion: Specific considerations tailored to metabolic syndrome, vitamin C and kidney diseases measured by ACR screening and monitoring mechanisms at the community level is critical to tackle further medical complications. Moreover, the role of VitC fortified foods on prevention of kidney diseases among patients with MetS warrant further investigation.

Introduction: Elevated albuminuria is an important outcome of diabetic complications and metabolic syndrome (MetS), the complex metabolic abnormalities manifested as glucose intolerance, hypertension, and dyslipidemia and enlarged waist circumference. These coexisting cardio-metabolic abnormalities are also associated with oxidative stress and low grade inflammation. Vitamin C (vitC) has long been recognized as hydrophilic antioxidant and blocker of oxidative stress which also has a protective role of MetS and kidney disease. Objective: The aim of this study was to identify the predictive effect of vitC deficiency on kidney disease among patients who developed metabolic syndrome. Method and procedures: To meet this objective, the National Health and Nutrition Examination Survey (NHANES) 2007-2008 data were used. NHANES represents the civilian, non-institutionalized US population data implemented for continuous system of monitoring health, nutritional status and well-being in the US. The predictive power of MetS on AU and vitC deficiency (vitC < 0.25 mg/dl) as effect modifier was assessed with binary logistic regression. Age, gender, race and BMI were used as covariates. Results: Among the respondents, 1.9% of the US population had risk of kidney damage, whereas 14.5 % of respondents had MetS. MetS was significantly positively correlated with AU (p < 0.01). Higher elevation of albuminuria creatinine ratio (ACR) was found in participants with VCD. The regression models developed in this study showed that the severity of kidney disease measured by ACR was increased among individuals who developed both VCD and MetS compared with individuals who developed MetS only (AOR=5.53; 95% CI: 2.73, 11.21). Increasing age and being African-American in race were independently associated with elevated AU. Conclusion: Specific considerations tailored to metabolic syndrome, vitamin C and kidney diseases measured by ACR screening and monitoring mechanisms at the community level is critical to tackle further medical complications. Moreover, the role of VitC fortified foods on prevention of kidney diseases among patients with MetS warrant further investigation.

Background Sarcopenia is a state with progressive and generalized loss of skeletal muscle mass and strength. It is a serious complication occurring in chronic kidney disease (CKD) patients which increases morbidity and mortality rate. Sarcopenia is diagnosed when loss of both compartments - muscle strength and skeletal muscle quality or quantity are present. However, there are still numerous patients, also with CKD, diagnosed as pre-sarcopenic individuals with low muscle strength and normal skeletal muscle quality or quantity and conversely, with correct muscle strength and decreased skeletal muscle mass, who are prone to develop sarcopenia in future life. It is crucial to examine numerous variables possibly associated with changes of skeletal muscle mass and muscle strength in terms of preventing the development of sarcopenia. The aim of the study was to investigate anthropometric and clinical correlates and sources of variation in both skeletal muscle mass and muscle strength in advanced stages of CKD. Methods The study sample consisted of 84 non-dialysis dependent patients of both sexes (including 45.2% of women) with eGFR < 45 ml/min/1.73m2: 26.2% with eGFR 30-44 mL/min/1.73 m2, 65.5% with eGFR 15-29 mL/min/1.73 m2 and 8.3% with eGFR < 15 mL/min/1.73 m2. Muscle strength was estimated by measuring hand grip strength (HGS) with the use of handheld hydraulic dynamometer. Muscle quantity was measured by bioimpedance spectroscopy using Body Composition Monitor. Appendicular skeletal muscle mass (ASM) was calculated according to Lin’s formula. Serum creatinine, urea, uric acid and albumin were measured. Results In bivariate analysis we found that ASM significantly and positively correlated with anthropometric variables such as body mass (r=0.903, p

There is a pressing need for more precise biomarkers of chronic kidney disease (CKD). Plasma samples from 820 subjects [231 with CKD, 325 with end-stage kidney disease (ESKD) and 264 controls] were analyzed by LC-MS/MS to determine a metabolic profile of 28 aminoacids (AA) and biogenic amines to test their value as markers of CKD risk and progression. The Kynurenine/Tryptophan ratio showed the strongest correlation with estimated glomerular filtration rate values (coefficient=-0.731, P&lt;0.0001). Models created with Orthogonal Partial Least Squares-Discriminant Analysis (OPLS-DA) containing the metabolic signature showed high goodness of fit and predictability for controls/CKD (R2X:0.73;R2Y:0.92;Q2:0.92) and lower for CDK/ESKD (R2X:0.56;R2Y:0.59;Q2:0.55). Based on generated VIP scores, the most relevant markers for segregating samples into control/CKD or CKD/ESKD groups were citrulline (1.67) and tryptophan (1.59), respectively. ROC analysis showed that the addition of the metabolic profile to a model including CKD classic risk factors improved AUC from 86.7% (83.6-89.9) to 100% (100-100) for CKD risk (P&lt;0.0001), and from 63.0% (58.2-67.8) to 96.5% (95.3-97.8) for the risk of progression from CKD to ESKD (P&lt;0.0001). Plasma concentrations of AA and related amines may be useful as diagnostic biomarkers of kidney disease, both for CKD risk and for progression of CKD patients to ESKD.

Chronic kidney disease is a critical health crisis in the US, affecting about 37 million adults. Known as "the silent killer" because it is often undiagnosed until it has reached a stage of progression. Renal dysfunction causes many adverse effects to the body's biological mechanisms, such as fluid electrolyte and pH balance, blood pressure regulation, excretion of toxins and waste, vitamin D metabolism, and hormonal regulation. Many CKD patients experience hyperkalemia, hyperphosphatemia, chronic metabolic acidosis, bone deterioration, blood pressure abnormalities, and edema. Symptoms experienced may be minimized, and the disease's progression may be slowed through an appropriate diet, which is why medical nutrition therapy is a critical aspect of the medical intervention for CKD. The current KDOQI recommendations are proposed as well as the physiological mechanisms behind the recommendations. Current biological explanations of the effects of a whole foods plant-based diet are included for possible contrast with the current renal diet. Strong evidence continues to support the importance of proper nutrition in the prevention and progression of kidney disease.

Renal angiogram is a promising tool for diagnosing renal vasculature and structural alterations in renal diseases. In renal diseases, the vascular changes were observed earlier than the structural and other changes. However, the literature on angiograms in kidney diseases was limited. Six client-owned dogs with chronic kidney diseases with International Renal Interest Society (IRIS) stage II and III were selected for this study. Under general anesthesia, the femoral arterial catheterization was performed. With a Cobra (C2) catheter, Iohexol saline (50:50) was administered to evaluate the vascular changes of Renal failure, using selective and non-selective angiograms. The procedures were completed successfully with minimal complications. Serum biochemistry and urine protein creatinine ratio were estimated sequentially and quality of life was monitored. Due to contrast agent complications, a dog died within 14 days and necropsy was conducted. Though the renal angiogram has complications, it is a reliable tool for the diagnosis of vasculature changes associated with kidney diseases, in veterinary medicine.

Chronic kidney disease (CKD) affects >10% of the adult population. Each year approximately 120,000 Americans develop end-stage kideny disease and initiate dialysis, which is costly and associated with functional impairments, worse health-related quality of life, and high early-mortality rates exceeding 20% in the first year. Recent declarations by the World Kidney Day and the U.S. Government Executive Order seek to implement strategies that reduce the burden of kidney failure by slowing CKD progression and controlling uremia without dialysis. Pragmatic dietary interventions may have a role in improving CKD outcomes and preventing or delaying dialysis initiation. Evidence suggests that a patient-centered plant-dominant low-protein diet (PLADO) of 0.6-0.8 g/kg/day comprised of >50% plant-based sources, administered by dietitians trained in non-dialysis CKD care, can be promising. The scientific premise of the PLADO is based on the observations that high protein diets with high meat intake are not only associated with higher cardiovascular disease risk but also higher CKD incidence and faster CKD progression due to increased intraglomerular pressure and glomerular hyperfiltration. Meat intake increases production of nitrogenous end-products, worsens uremia, and may increase the risk of hyperkalemia, given constipation from the typical low fiber intake. Plant-dominant, fiber-rich, low-protein diet may lead to favorable alterations in the gut microbiome, which can modulate uremic toxin generation and slow CKD progression, along with reducing cardiovascular risk in CKD patients. PLADO is a heart-healthy, safe, flexible, and feasible diet that could be the centerpiece of a conservative and preservative CKD-management strategy that challenges the prevailing dialysis-centered paradigm.

Recent studies have demonstrated a relationship between poor vitamin D status and respiratory infections and diarrhea among young children. Acute lower respiratory infections (ALRI) and diarrhea are among the two most important causes of death in under-5 children. In this analysis, we examine the extent to which vitamin-D deficiency (<10 ng/ml) predicts these outcomes using data from a randomized controlled trial (RCT) of daily folic acid and/ or vitamin B12 supplementation for six months in 6 to 30 months old children conducted in Delhi, India. Of the 960 subjects who had vitamin-D concentrations measured, 331(34.5%) were vitamin-D deficient. We found, after controlling for relevant potential confounders (age, sex, breastfeeding status, wasting, stunting, underweight, anemia status at base line and season), the risk of ALRI was significantly higher among vitamin-D deficient (OR 1.26; 95% CI: 1.03 to 1.55) compared to vitamin-D-replete children in the six months follow-up period. Vitamin-D status was not significantly associated with episodes of diarrhea and clinical pneumonia. The extent of causal relationship of vitamin-D status and ALRI needs to be explored in further studies.

Automated medical diagnosis is one of the important machine learning applications in the domain of healthcare. In this regard, most of the approaches primarily focus on optimizing the accuracy of classification models. In this research, we argue that unlike general-purpose classification problems, medical applications, such as chronic kidney disease (CKD) diagnosis, require special treatment. In the case of CKD, apart from model performance, other factors such as the cost of data acquisition may also be taken into account to enhance the applicability of the automated diagnosis system. In this research, we have proposed two techniques for cost-sensitive feature ranking. An ensemble of decision tree models is employed in both the techniques for computing the worth of a feature in the CKD dataset. An automatic threshold selection heuristic is also introduced which is based on the intersection of features’ worth and their accumulated cost. A set of experiments are conducted to evaluate the efficacy of the proposed techniques on both tree-based and non-tree based classification models. The proposed approaches are also evaluated against several comparative techniques. Furthermore, it is demonstrated that the proposed techniques select around 1/4^th of the original CKD features while reducing the cost by a factor of 7.42 of the original feature set. Based on the extensive experimentation it is concluded that the proposed techniques employing feature-cost interaction heuristic tend to select feature subsets that are both useful and cost-effective.

.Cellular senescence has emerged as an important driver of aging and age-related disease in the kidney. The activity of β-galactosidase at pH 6 (SA-β-Gal) is a classic maker of senescence in cellular biology. However the predictive role of kidney tissue SA-β-Gal on eGFR loss in chronic kidney disease (CKD) is still not understood. We retrospectively studied the expression of SA-β-Gal in kidney biopsies obtained in a cohort [n=29] of incident patients who were followed up for 3 years as for standard of care. SA-β-Gal staining was approximately 4-fold higher in the tubular compartment of patients with CKD vs. controls [26.0 ± 9 vs. 7.4 ± 6% positive tubuli in patients vs. controls; p < 0.025]. Tubular expressions of SA-β-Gal, but not proteinuria at the time of biopsy correlated with eGFR loss at follow-up; moreover, SA-β-Gal expression in more than 30% of kidney tubules was associated with fast progressive kidney disease. In summary, our study shows that SA-β-Gal is upregulated in the kidney tubular compartment of adult patients affected by CKD, and suggests that tubular SA-β-Gal is associated with accelerated loss of renal function.

Microbiota-based strategies are a novel auxiliary therapeutic and preventative way of moderating chronic kidney disease. Lactobacillus mixture (Lm) was previously demonstrated to exert a renal-protective function in the CKD mice model. The efficacy of probiotics in pet foods is a relatively new area of study, and thus verifying the potential health benefits is necessary. This study evaluated the efficacy of Lm treats in feline CKD and elucidated the mechanisms underlying host-microbe interactions. CKD cats (2 and 3 stages) were administrated probiotic pet treats daily (10 g) for 8 weeks. The results demonstrated that during the eight weeks of Lm administration, creatinine was reduced or maintained in all cats with CKD. Similarly, gut-derived uremic toxins (GDUT), IS, and TMAO were significantly downregulated in the serum (confidence intervals = 90%). The life quality of the cats also improved. Feline gut microbiome data, KEGG pathway, and renal function indicator analyses revealed the possible mechanisms involved in modulating CKD feline microbial composition. Further regulation of the microbial functions in amino acid metabolism after Lm administration contributed to downregulating deleterious IS, PCS, and TMAO. The current study provides potential adjuvant therapeutic insights into probiotic pet foods or treats for pets with CKD.

In March 2013, a novel avian influenza A H7N9 virus was emerged in China, which cause rapidly progressive pneumonia and with a high fatality rate. Serologic studies to evaluate neutralizing antibodies of infected patients and birds are invaluable tools for immunogenicity research of H7N9 and epidemiological investigation. Conventional neutralization assays are laborious and time-consuming which also hampered by biosafety requirement. In this study, We construct and produce pseudovirus bearing the full-length hemagglutinin (HA) of H7N9 virus in the Env-defective, luciferase-expressing HIV-1 backbone. The production of lentiviral pseudovirus was analysed by HA gene specific real-time reverse-transcription PCR, transmission electron microscopy (TEM), and Western Blot assay to prove the nucleic acid replication, the morphology of virus, and the expression of HA protein in pseudovirus. After that pseudovirus based inhibition assay was established to detect neutralizing antibodies of a panel of serum samples. Our results demonstrated that H7N9 pseudovirus which had single-cycle infection was generated. By comparing the neutralization antibody titers, pseudovirus based neutralization test could be recognized as an alternative of conventional microneutralization (MN). Hence, we conclude that it is possible to use pseudovirus inhibition assay to screen sera samples, as well as evaluate vaccine-induced neutralizing antibodies against H7N9 virus.

Introduction: Increased oxidative stress, including elevated homocysteine (Hcy) plasma levels, and lowered levels of antioxidants participate in the pathophysiology and progression of chronic kidney disease (CKD). Paraoxonase (PON)1 activity and folic acid are antioxidants which play a role in Hcy metabolism. However, there are no data whether, in CKD, treatment with folic acid improves glomerular filtration rate (GFR) through effects on PON1 activity and Hcy concentrations. Methods: In the current study, we determined PON1 genotypes and activity, Hcy and estimated GFR (eGFR) both before and after treatment with folic acid (5 mg/d) versus no treatment during three consecutive months in 113 outpatients with CKD classified into stages 4, 3b and 3a. Results: PON1 CMPAase and AREase activities were significantly lower in patients allocated to CKD stage 4 as compared with stages 3b and 3a. Treatment with folic acid significantly improved eGFR and increased levels of CMPAase and AREase in patients allocated to classes 4 and 3b, but not 3a. The improvement of eGFR was associated with increased CMPAase and AREase activities, while the latter were associated with increased levels of folic acid. Treatment with folic acid significantly reduced plasma Hcy levels and the Hcy/PON1 activity ratio. The effects of folic acid increasing PON1 activities were not mediated by changes in Hcy. Discussion: Treatment of CKD patients in early/intermediate stages of CKD patients improves oxidative stress by rebalancing the prooxidant (Hcy) / antioxidant (PON1 activities) ratio. Treatment with folic acid significantly improves eGFR and these effects are mediated via increased PON1 activities. Treatment with folic acid in phase G3b and G4 may reduce renal disease progression by enhancing antioxidant defenses.

Vitamin D status may impact acute affective symptomatology and the severity of symptoms in patients with bipolar disorder (BD). Therefore, this cross-sectional study analyzed 25(OH)D, 24,25(OH)2D, and the vitamin D metabolite ratio (VMR) in BD and correlated the results with clinical affective symptomatology and functionality. The inactive precursor 25(OH)D and its principal catabolite 24,25(OH)2D were measured simultaneously with a validated liquid chromatography tandem mass-spectrometry method in 170 BD outpatients and 138 healthy controls. VMR was calculated as follows: VMR=100*(24,25(OH)2D/25(OH)D). The psychometric assessment enclosed: Beck Depression Inventory-II, Hamilton Depression Rating Scale, Young Mania Rating Scale, Global Assessment of Functioning, and number of suicide attempts. We did not find a significant difference between patients and controls in the concentrations of 25(OH)D and 24,25(OH)2D. Additionally, the VMR was comparable in both groups. The calculations for the clinical parameters showed a negative correlation between the Young Mania Rating Scale and 24,25(OH)2D (r = -.154, p = .040). Based on the small effect size and the predominantly euthymic sample, further exploitation in individuals with manic symptoms would be needed to confirm this association. In addition, long-term clinical markers, and an assessment in different phases of the disease may provide available additional insights.

Obesity has become a global epidemic, contributing to the development of numerous chronic diseases, including diabetes, chronic kidney disease (CKD) and cardiovascular disorders. MicroRNAs (miRNAs) have emerged as key regulators in various biological processes, including metabolism, inflammation, and tissue remodeling, making them pivotal players in obesity-related pathologies. This review aims to provide comprehensive insights into the roles of miRNAs in obesity, with a particular emphasis on their involvement in the pathogenesis of CKD and cardiovascular disorders. We highlight the involvement of specific miRNAs in adipose tissue development, energy homeostasis, inflammation, and insulin resistance, contributing to the pathogenesis of obesity. Moreover, we explore the impact of miRNAs on renal fibrosis, and inflammation, giving clues on their roles in the development and progression of CKD. Additionally, we discuss the influence of miRNAs on endothelial dysfunction, atherosclerosis, and cardiac remodeling, emphasizing their contribution to obesity-related cardiovascular disorders. Understanding the regulatory functions of miRNAs in these interconnected conditions holds promise for improved diagnosis, prognosis, and therapeutic interventions. Indeed, miRNAs are potential diagnostic biomarkers for obesity-related diseases although challenges remain to be elucidated before their clinical translation. Furthermore, we highlight the emerging strategies that target miRNAs as therapeutic interventions to mitigate the detrimental effects of obesity on kidney and cardiovascular health.

Background: Biomarker development, improvement, and clinical implementation in the context of kidney disease has been a central focus of biomedical research for decades. To this point, only serum creatinine and urinary albumin excretion are well accepted biomarkers in kidney disease. With their known blind spot in early stages of kidney impairment and diagnostic limitations there is a need for better and more specific biomarkers. With the rise of large-scale analysis of thousands of peptides in serum or urine samples using mass spectrometry techniques hopes for biomarker development were high. Advances in proteomic research have led to the discovery of an increasing amount of potential proteomic biomarkers and identification of candidate biomarkers for clinical implementation in the context of kidney disease management. In this review we focus on urinary peptide and especially peptidomic biomarkers emerging from recent research and underline the role of those with the highest potential for clinical implementation. Methods: The Web of Science database (all databases) was searched on October 17th, 2020, using the search terms “marker*” OR biomarker* AND “renal disease” OR “kidney disease” AND “proteome*” OR “peptid*” AND “urin*”. English, full-text original articles on humans published within the last 5 years were included which were cited at least 5 times per year. Studies based on animal models, renal transplant studies, metabolite studies, studies on miRNA and studies on exosomal vesicles were excluded focusing on urinary peptide biomarkers. Results: The described search led to the identification of 3668 articles and application of inclusion and exclusion criteria as well as abstract and consecutive full-text analysis of 3 independent authors to a final number of 62 studies for this manuscript. The 62 manuscripts encompassed 8 established single peptide biomarkers and several proteomic classifiers including CKD273 and IgAN237. Discussion: This review provides a summary of recent evidence on single peptide urinary biomarkers in CKD while emphasizing the increasing role of proteomic biomarker research with new research on established and new proteomic biomarkers. Lessons learned from the last 5 years in this review might encourage future studies hopefully resulting in routine clinical applicability of new biomarkers.

In our country, the aging society is rapidly progressing, with an increase in patients with chronic kidney disease (CKD) and those undergoing dialysis, coupled with the aging of the population. As a result, the number of individuals with cognitive impairment (CI) is rising, and addressing this issue has become an urgent problem. One characteristic of dementia in CKD patients is the high frequency of vascular dementia, making the prevention through the management of classical risk factors such as hypertension, diabetes mellitus, dyslipidemia, smoking, etc., associated with atherosclerosis and arteriosclerosis. Other effective measures, including the use of renin-angiotensin system inhibitors, addressing anemia, exercise therapy, and lifestyle improvements, have been reported. Incidence and progression of CI may also be influenced by the type of dialysis or kidney replacement therapy, with reports suggesting that long-duration dialysis, low-temperature hemodialysis, peritoneal dialysis, and kidney transplantation (KTx) can have a possible preferable effect on preserving cognitive function.

Body composition measurement plays an important auxiliary role in the nutritional assessment of diseases, nutritional diagnosis and the evaluation of the effect of nutritional therapy. There are many techniques and methods available for the measurement of body composition. Bioelectrical impedance analysis (BIA ) of body composition has been widely used and explored in many diseases in the past 30 years. Its main advantages are its non-invasiveness, non-radiation, economy, convenience and feasibility. With the development of bioelectrical impedance technology, bioelectrical impedance analysis has gradually developed from single-frequency BIA (SF-BIA) to dual-frequency BIA (DF-BIA). now devices are available that measure at multiple fixed frequencies (multi-frequency BIA, MF-BIA) and over a range of frequencies (bioimpedance spectroscopy, BIS). The clinical significance of nutrition management in chronic kidney disease has gradually become prominent. Bioelectrical impedance analysis of body composition is favored by nephrologists and nutritionists as an auxiliary method for nutrition diagnosis, treatment and monitoring. In the past 20 years, there have been many studies on body composition measurement by bioelectrical impedance analysis in the nutritional management of CKD patients. This article will summarize the recent research results of BIA of body composition method in the nutrition management of CKD patients in pre-dialysis, hemodialysis, peritoneal dialysis and kidney transplantation, in order to provide reference for the application and research of BIA method in the nutrition management of chronic kidney disease in the future.

Diabetes and chronic kidney disease (CKD) are a major public health burden in low-and-middle-income countries. This study aimed to explore factors associated with CKD in patients with type 2 diabetes (T2D) in Bangladesh. A cross-sectional study was conducted among 315 adults with T2D presenting at the outpatient department of Bangladesh Institute of Health Sciences (BIHS) hospital between July 2013 to December 2013. CKD was diagnosed based on estimated Glomerular Filtration Rate using the ‘Modification of Diet in Renal Disease’ equations and presence of albuminuria estimated by the albumin-to-creatinine ratio. Multivariate logistic regression analysis was used to determine the factors associated with CKD. The overall prevalence of CKD among patients with T2D was 21.3%. In the unadjusted model Factors associated with CKD were: aged 40-49 years (OR: 5.7, 95% CI: 1.3-25.4), age 50-59 years (7.0, 1.6-39), age ≥60 years (7.6, 1.7-34); being female (2.2, 1.2-3.8), hypertensive (1.9, 1.1-3.5) and household income between 128.2-256.4 US$ (2.9, 1.0-8.2) compared with income ≤128.2$. However, after adjustment of other covariates, only duration of hypertension and household income (128.2-256.4 US$) remained statistically significant. There is a need to implement policies and programs for early detection and management of hypertension and CKD in T2D patients in Bangladesh.

Background: We investigated ion channels at the skin, including peripheral nerve endings, which serve as output machines and molecular integrators of many pruritic inputs mainly received by multiple G protein-coupled receptors (GPCRs). Methods: Based on the level of chronic kidney disease–associated pruritus (CKD-aP), subjects were divided into two groups: non-CKD-aP (no or slight pruritus; n=12) and CKD-aP (mild, moderate, or severe pruritus; n=11). Skin samples were obtained from the forearm or elbow during operations on arteriovenous fistulas. We measured ion channels expressed at the skin, including peripheral nerve endings by RT-PCR: Nav1.8, Kv1.4, Cav2.2, Cav3.2, BKCa, Anoctamin1, TRPV1, TRPA1, and ASIC. Results: Expression of Cav3.2, BKCa, and anoctamin1 was significantly elevated in patients with CKD-aP. On the other hand, expression of TRPV1 was significantly reduced in these patients. We observed no significant difference in the levels of Cav2.2 or ASIC between subjects with and without CKD-aP. TRPA1, Nav1.8，and Kv1.4 were not expressed. Conclusions: It was concluded that this greater difference in expression of ion channels at the skin tissue including specific for cutaneous peripheral nerve endings in CKD patients with CKD-aP may increase generator potential related to itching.

Study Objectives: The aim of this study is to explore the association between serum 25-hydroxyvitamin D [25(OH)D] levels, a marker of Vitamin D status, and excessive daytime sleepiness (EDS), expressed as increased scores of Epworth Sleepiness Scale (ESS), in a group of prospectively enrolled patients with obstructive sleep apnea (OSA). Methods: Newly diagnosed patients with OSA, divided into two groups, those with EDS (ESS>10) and those without EDS (ESS

Despite the successful introduction of oral cholera vaccines, Zambia continues to experience multiple, sporadic, and protracted cholera outbreaks in various parts of the country. While vaccines have been useful in staying the cholera outbreaks, the ideal window for re-vaccinating individual’s resident in cholera hotspot areas remains unclear. Using a prospective cohort study design, 225 individuals were enrolled, re-vaccinated with two doses of Shanchol™ regardless of previous vaccination and followed-up for 90 days. Bloods collected at baseline before re-vaccination, at day 14 prior to second dosing and subsequently on days 28, 60, and 90. Vibriocidal assay was performed on samples collected at all five time points. Our results showed that anti-LPS and vibriocidal antibody titers increased at day 14 after re-vaccination and decreased gradually at 28, 60 and 90 across all the groups. Seroconversion rates were generally comparable in all treatment arms. We therefore conclude that vibriocidal antibody titers generated in response to re-vaccination still wane quickly irrespective of previous vaccination status. However, despite the observed decline, the levels of vibriocidal antibodies remained elevated over baseline values across all groups, an important aspect for Zambia where there is no empirical evidence as to the ideal time for re-vaccination.

The study investigated the relationships between sarcopenia, frailty, and related factors in hemodialysis patients with chronic kidney disease. A prospective cross-sectional study with convenience sampling was conducted between August 2021 and February 2022 at a hospital-affiliated hemodialysis center. Ninety-six hemodialysis patients participated in the study. Quantitative data were collected with structured interviews. Sarcopenia was determined with a rapid screening tool. Frailty was determined with the Rockwood clinical frailty score. Descriptive analysis, Person Correlations, and Linear regression analysis were used to evaluate the associations between frailty, sarcopenia, and health-related factors in hemodialysis patients. The mean age of the participants was 65.4 11.5 years, with an average of 95.0 77.5 months of hemodialysis. The most common comorbidity was hypertension (72.9%), followed by diabetes mellitus (39.6%) and cardiovascular health problems (35.4%). A significant difference in frailty between sarcopenia patients and a healthy population (X2 =9.51, p &lt;.001) was identified. There was a strong negative correlation (r= −.853, p&lt;.001) between sarcopenia and frailty, while moderate correlations between sarcopenia and frailty in sarcopenia patients (r= −.66, p&lt;.001) and a healthy population (r= −.58, p&lt;.001) were observed. Age, body weight before dialysis, and hand grip strength were found to be potential predictors of sarcopenia and frailty. Left calf circumference was significantly associated with sarcopenia (ß= −.128, p = .049). Age, body weight before dialysis, and hand grip strength are potential predictors of sarcopenia and frailty in hemodialysis patients with chronic kidney disease. Comorbidities, which may be preventable, are common in this population.

Chronic kidney disease (CKD) bears a heavy burden on patients and the health care system as whole. The incidence of CKD has been increasing in the Arab world over the years due to increases in Diabetes and hypertension which are the most prominent causes of CKD. Syrians are at higher risk for diabetes and hypertension due to the crisis that the country has been going through. 297 patients’ charts were examined in the kidney surgical hospital in Damascus Syria to determine risk factors for CKD, prevalence of diabetes among them and its associating demographic factors along with changes in serum creatinine, urea, fasting blood glucose levels and MDRD score among diabetic CKD patients. 64.6% of patients were above 50, 61.6% were males and 35.4% were diabetic. Patients with diabetes had lower creatinine levels upon admission than non-diabetics. The correlation between fasting blood glucose level and serum creatinine, urea and MDRD was not statistically significant. This paper shows that the prevalence of diabetes among CKD patients is similar in Syrians to the rest of the world despite the increase of diabetes incidence.

Background: According to newly published studies, patients with Coronavirus Disease 2019 (COVID-19) have significantly lower serum 25-hydroxyvitamin D 25(OH)D levels than those without the SARS-CoV-2 infection. Vitamin D insufficiency may be a predictor of poor prognosis in COVID-19 patients. Vitamin D supplementation is related to improved clinical outcomes in terms of intensive care unit (ICU) admission and death, particularly in individuals with moderate-to-severe forms of COVID-19 requiring hospitalization. Materials and methods: This placebo-controlled five-day study was performed on 100 hospitalized COVID-19 patients with vitamin D insufficiency randomized into two groups. Vitamin D in the form of a sublingual sprayable microemulsion (LYL love your life® sunD3 LYLmicro™) was given three times daily after breakfast, lunch, and dinner (daily dose 12,000 IU) to 52 patients with blood vitamin D levels below 30 ng/ml. 48 patients in the control group received a placebo spray in the same daily regiment. Results: We observed a statistically significant increase by 8.6 ng/ml in median vitamin D level after five days of high-dose vitamin D3 spray therapy. 90.2% of subjects reached normal serum levels of vitamin D. There was a strong correlation between changes in vitamin D and C-reactive protein (CRP) levels in individuals with moderately severe disease (p<0.05), while mild and severe cases showed no statistical significance comparing case and control groups. There were no statistically significant changes in ferritin and interleukin-6 (IL-6) levels. Conclusions: In this study, we demonstrated the possibility to rapidly increase circulating levels of vitamin D just in 5 days of high-dose intervention and found a statistically significant decrease of CRP levels in patients with moderately severe COVID-19. We were not able to detect statistically significant changes in ferritin and IL-6 levels during the 5-day vitamin D intervention.

Vitamin D, unlike the micronutrients, vitamins A, E and K, is largely obtained, not from food, but by the action of solar UV light on its precursor, 7-dehydrocholesterol, in skin. With the decline in UV light intensity in winter, most skin production of vitamin D occurs in summer. Because no defined storage organ or tissue has been found for vitamin D, it has been assumed that adequate vitamin D status in winter can only be maintained by oral supplementation. Skeletal muscle cells have now been shown to incorporate the vitamin D-binding protein (DBP) from blood into the cell cytoplasm where it binds to cytoplasmic actin. This intracellular DBP provides an array of specific binding sites for 25-hydroxyvitamin D (25(OH)D) which diffuses into the cell from the extracellular fluid. When intracellular DBP undergoes proteolytic breakdown, the bound 25(OH)D is then released and diffuses back into blood. This uptake and release of 25(OH)D by muscle, accounts for the very long half-life of this metabolite in the circulation. As 25(OH)D concentration in blood declines in winter, its cycling in and out of muscle cells appears to be upregulated. Parathyroid hormone is the most likely factor enhancing the repeated cycling of 25(OH)D between skeletal muscle and blood. This mechanism appears to have evolved to maintain adequate vitamin D status in winter.

Vitamin D, unlike the micronutrients, vitamins A, E and K, is largely obtained, not from food, but by the action of solar UV light on its precursor, 7-dehydrocholesterol, in skin. With the decline in UV light intensity in winter, most skin production of vitamin D occurs in summer. Because no defined storage organ or tissue has been found for vitamin D, it has been assumed that adequate vitamin D status in winter can only be maintained by oral supplementation. Skeletal muscle cells have now been shown to incorporate the vitamin D-binding protein (DBP) from blood into the cell cytoplasm where it binds to cytoplasmic actin. This intracellular DBP provides an array of specific binding sites for 25-hydroxyvitamin D (25(OH)D) which diffuses into the cell from the extracellular fluid. When intracellular DBP undergoes proteolytic breakdown, the bound 25(OH)D is then released and diffuses back into blood. This uptake and release of 25(OH)D by muscle, accounts for the very long half-life of this metabolite in the circulation. As 25(OH)D concentration in blood declines in winter, its cycling in and out of muscle cells appears to be upregulated. Parathyroid hormone is the most likely factor enhancing the repeated cycling of 25(OH)D between skeletal muscle and blood. This mechanism appears to have evolved to maintain adequate vitamin D status in winter.

Background: Patients with severe chronic kidney disease (CKD G4-G5) often have chronically elevated high-sensitivity cardiac troponin T (hs-cTnT) values above the 99th percentile of the upper reference limit. In these patients, optimal cutoff levels for diagnosing non-ST-elevation acute cor-onary syndrome (NSTE-ACS) requiring revascularization remain undefined. Methods: Of 11,912 patients undergoing coronary angiography from 2012 to 2017 for suspected NSTE-ACS, 325 (3%) had severe CKD. Of these, 290 with available serial hs-cTnT measurements were included and 300 matched patients with normal renal function were selected as a control cohort. Results: Diagnostic performance for patients with severe CKD was high at presentation and similar to that of the control population (AUC, 95% CI: 0.81, 0.75-0.87 versus 0.85, 0.80-0.89, p=0.68) and the ROC-derived cutoff value at presentation was 4 times higher compared to the conventional 99th percentile. Combining the ROC-derived cutoff levels for hs-cTnT at presentation and absolute 3-hour changes, sensitivity increased to 98%, PPV and NPV improved up to 93% and 86%, re-spectively. (4) Conclusions: In patients with severe CKD and suspected ACS the diagnostic accu-racy of hs-cTnT for the diagnosis of NSTE-ACS requiring revascularization is improved by using higher assay specific cutoff levels combined with early absolute changes.

Background: This study aimed to identify the association between occupational stress and depression-well-being by proposing a comprehensive and flexible job burden-capital model with its corresponding hypotheses. Methods: For this research, 1618 valid samples were gathered from the electronic manufacturing service industry in Hunan Province, China; self-rated questionnaires were administered to participants for data collection after obtaining their written consent. The proposed model was fitted and tested through structural equation model analysis. Results: Single-factor correlation analysis results indicated that coefficients between all items and dimensions had statistical significance. The final model demonstrated satisfactory global goodness of fit (CMIN/DF=5.37, AGFI=0.915, NNFI=0.945, IFI=0.952, RMSEA=0.052). Both the measurement and structural models showed acceptable path loadings. Job burden and capital were directly associated with depression and well-being or indirectly related to them through personality. Multi-group structural equation model analyses indicated general applicability of the proposed model to basic features of such a population. Gender, marriage and education led to differences in the relation between occupational stress and health outcomes. Conclusions: The job burden-capital model of occupational stress-depression and well-being was found to be more systematic and comprehensive than previous models.

Breath volatile organic compound analysis is a non-invasive tool for assessing health status; the compositional profile of these compounds in the breath of patients with chronic kidney disease is believed to change with decreasing renal function. We aimed to identify breath volatile organic compounds for recognizing patients with chronic kidney disease. Using thermal desorption-gas chromatography-mass spectrometry, untargeted analysis of breath markers was performed using breath samples of healthy controls (n=18) versus non-dialysis (n=21) and hemodialysis (n=12) patients with chronic kidney disease in this cross-sectional study. A total of 303 volatile organic compounds alongside 12 clinical variables were used to determine the breath volatile organic compound profile. Metabolomic analysis revealed that age, systolic blood pressure, and fifty-eight breath volatile organic compounds differed significantly between the chronic kidney disease group (non-dialysis + hemodialysis) and healthy controls. Thirty-six volatile organic compounds and two clinical variables that showed significant associations with chronic kidney disease in the univariate analysis were further analyzed. Different spectras of breath volatile organic compounds between the control and chronic kidney disease groups were obtained. Multivariate model incorporating age, 2-methyl-pentane, and cyclohexanone showed high performance (accuracy, 86%) in identifying patients with chronic kidney disease, with odds ratios (95% confidence interval) P-values of 0.18 (0.07-2.49) 0.013; 2.10 (0.94-2.24) 0.025; and 2.31 (0.88–2.64) 0.008, respectively. Hence, renal dysfunction-associated characteristic profiles of breath volatile organic substances can be used as non-invasive markers to screen for chronic kidney disease.

Vitamin D plays an important role in maintaining healthy mineralized skeleton. It is also consid-ered an immunomodulatory agent that regulate the innate and adaptive immune systems. Multi-ple observational studies have demonstrated the association between low level of serum 25-hydroxyvitamin D [25(OH)D] and presence and severity of several rheumatic diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), spondyloarthropathies and oste-oarthritis (OA). Nevertheless, the specific benefits of vitamin D supplement for treatment and prevention of rheumatic diseases are less accepted as the results from randomized clinical trials are inconsistent, although some conceivable benefits of vitamin D for improvement of disease ac-tivity of RA, SLE and OA have been demonstrated in meta-analyses. It is also possible that some individuals might benefit from vitamin D differently from others since inter-individual difference in responsiveness to vitamin D supplementation has been observed in genomic studies. Although the optimal level of serum 25(OH)D is still debatable, it is advisable it is advisable that patients with rheumatic diseases should maintain serum 25(OH)D level at least 30 ng/mL (75 nmol/L) to prevent osteomalacia, secondary osteoporosis and fracture, and possibly 40 – 60 ng/mL (100 – 150 nmol/L) to achieve maximal benefit from vitamin D for immune health and overall health.

Apis mellifera, especially weak ones, are highly vulnerable to Carpoglyphus lactis mites, which can rapidly infest and consume stored pollen, leading to weakened colonies and potentially colony collapse. This study aimed to ascertain and investigate the prevalence of this mite in honeybee colonies across 9 provinces in the Republic of Korea (ROK). A total of 615 honeybee colonies were collected, from 66 apiaries during the spring and 58 apiaries during the summer of 2023. A 1,242 bp segment of the the Cytochrome c oxidase subunit 1 (COI) gene was amplified using the polymerase chain reaction method. The detection levels of C. lactis in the honeybees were compared between winter and summer. Based on the COI sequence analysis, the nucleotide sequence similarity of C. lactis mites isolated in the ROK with those from China (NC048990.1) was found to be 99.5%, and with those from the United Kingdom (KY922482.1) was 99.3%. This study is the first report of C. lactis in Korean apiaries. The findings in this study demonstrate a significantly higher detection rate in winter, which is 4.1 times greater than that in summer (p &lt; 0.001). Furthermore, the results underscore the usefulness of molecular diagnostic techniques for detecting C. lactis mites.

Gut microbiota dysfunction is a key factor affecting chronic kidney disease (CKD) susceptibility. Puerariae Lobatae Radix (PLR), a traditional Chinese medicine and food homologous herb, is known to promote gut microbiota homeostasis, however, its role in renoprotection remains unknown. This study aimed to investigate the efficacy and potential mechanism of PLR to alleviate CKD. An 8-week 2% NaCl-feeding murine model was applied to induce CKD and evaluate the therapeutic effect of PLR supplementary. After gavage for 8 weeks, PLR significantly alleviated CKD-associated creatinine, urine protein increasement and nephritic histopathological injury. Moreover, PLR protected kidney from fibrosis by reducing inflammatory response and down-regulating the canonical Wnt / β-catenin pathway. Further, PLR rescued gut microbiota dysbiosis and protected high salt-induced gut barrier dysfunction. We found enrichment of Akkermansia and Bifidobacterium after PLR intervention, the relative abundance of which were in positive correlation with normal maintenance of renal histology and function. Next, fecal microbiota transplantation experiment verified that the positive effect of PLR on CKD was at least partially exerted through gut microbiota reestablishment and down-regulation of the Wnt / β-catenin pathway. Our study provides evidence for new function of PLR on kidney protection and put forward a potential therapeutic strategy target for CKD.

Background: Initial phases of molecular and cellular maladaptive bone response at early CKD remain mostly unknown. Methods: We induced mild CKD in SHRs by either arterial hypertension lasting six months (sham-operated rats, SO6) or in its’ combination with 3/4 nephrectomy lasting two and six months (Nx2 and Nx6, correspondently). Sham operated SHRs (SO2) and Wistar Kyoto rats (WKY2) with two-month follow-up served as controls. Animals were fed standard chow containing 0.6% phosphate. We measured creatinine clearance, urine albumin-to-creatinine ratio, renal interstitial fibrosis, inorganic phosphate (Pi) exchange, intact PTH and FGF23, Klotho, dickkopf-1, sclerostin. And assessed bone response by static histomorphometric indices and gene expression profiles. Results: Mild CKD groups had no increase in renal Pi excretion, FGF23 and PTH levels. Serum Pi, dickkopf-1, and sclerostin were higher in Nx6. Decrease in trabecular bone area and osteocyte number was obvious in SO6. Nx2 and Nx6 had additionally lower osteoblast number. The decline in eroded perimeter was only apparent in Nx6. Significant downregulation of genes related to Pi transport, MAPK, WNT, and BMP signaling accompanied histological alterations in Nx2 and Nx6. Conclusions: We found an association of mild CKD with histological and molecular features suggesting lower bone turnover, which occurred at normal levels of systemic Pi-regulating factors.

In the last decade, an increasing awareness was directed to the role of Vitamin D in non-skeletal and preventive roles for chronic diseases. Vitamin D is a key hormone involved in the regulation of calcium/phosphorous balance and it has been implicated in the pathogenesis of inflammation, insulin resistance and obesity. Cholecalciferol (Vitamin D3) and Ergocalciferol (Vitamin D2) are the main form of vitamin D: the active form (1,25-dihydroxyvitamin D) is the result of two hydroxylations that take place in liver, kidney, pancreas and immune cells. Some anti-inflammatory cytokines are produced at higher levels by vitamin D, while some pro-inflammatory cytokines are released at lower levels. Toll-Like Receptor (TLR) expression is increased and a pro-inflammatory state is also linked to low levels of vitamin D. Regardless of how it affects inflammation, various pathways suggest that vitamin D directly improves insulin sensitivity and secretion. The level of vitamin D in the body may change the ratio of pro- to anti-inflammatory cytokines, which would impact insulin action, lipid metabolism, and the development and function of adipose tissue. Many studies have demonstrated an inverse relationship between vitamin D concentrations and pro-inflammatory markers, insulin resistance, glucose intolerance, metabolic syndrome, obesity and cardiovascular disease. It's interesting to note that several long-term studies also revealed an inverse correlation between vitamin D level and the occurrence of diabetes mellitus. Vitamin D supplementation in people has controversial effects, in fact while some studies demonstrated improvements in insulin sensitivity, glucose and lipid metabolism, others revealed no significant effect on glycemic control and inflammation. The aim of this review is to provide insight into the molecular basis of the relationship between vitamin D, insulin-resistance, metabolic syndrome, type 1 and 2 diabetes, gestational diabetes, and cardiovascular diseases.

This study was to investigate and assess salivary biomarkers as a means of diagnosing periodontitis. A total of 121 subjects were included: 28 periodontally healthy subjects, 24 with stage I, 24 with stage II, 23 with stage III, and 22 with stage IV periodontitis. Salivary proteins including active matrix metalloproteinase-8 (MMP-8), pro-MMP-8, total MMP-8, C-reactive protein, secretory immunoglobulin A and planktonic bacteria including Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Fusobacterium nucleatum, Prevotella intermedia, Porphyromonas nigrescens, Parvimonas micra, Campylobacter rectus, Eubacterium nodatum, Eikenella corrodens, Streptococcus mitis, Streptococcus mutans, Staphylococcus aureus, Enterococcus faecalis, and Actinomyces viscosus were measured from salivary samples. The performance of the diagnostic models was assessed by receiver operating characteristics (ROC) and area under the ROC curve (AUC) analysis. The diagnostic models were constructed based on the subjects’ proteins and/or microbial profiles, resulting in two potential diagnosis models, which achieved better diagnostic powers with an AUC value &gt; 0.750 for the diagnosis of stage II, III, and IV periodontitis (Model PC-I; AUC: 0.796, sensitivity: 0.754, specificity: 0.712) and for the diagnosis of stage III and IV periodontitis (Model PC-II; AUC: 0.796, sensitivity: 0.756, specificity: 0.868). This study can contribute to screening for periodontitis based on salivary biomarkers.

Healthy life style is associated with decreased risk of chronic kidney disease (CKD) and mortality in the general population. However, there is no definitive evidence on the benefits of physical activity and other health-related behaviors in the early-stage CKD. This study aimed to explore the association between health-related behaviors and end-stage renal disease (ESRD) and mortality in the early stages of CKD. The National Health Insurance Service (NHIS) database from January 1st, 2009 to December 31st, 2016 was used to screen 83,470 subjects with early stage CKD. Cox proportional hazard regression analysis was used to evaluate the association between health-related behaviors and ESRD and death. Kaplan-Meier curves for mortality and ESRD were plotted according to the physical activity, smoking status and alcohol consumption pattern. Risk of death decreased significantly in subjects who engaged in sufficient physical activity (adjusted Hazard Ratio (HR) 0.73; 95% CI: 0.64-0.83; p < 0.001). Risk of ESRD and death increased significantly in the current smoker with adjusted HR of 1.44 (95% CI: 1.06-1.95; p < 0.02) and 1.61 (95% CI: 1.44-1.80; p < 0.001) respectively. Therefore, systematic interventions to encourage physical activity and smoking cessation need to be actively considered in the early stages of CKD.

Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal0 tract (GIT), including Crohn’s disease (CD) and ulcerative colitis (UC), which differ in the location and lesion extensions. Both diseases are associated with microbiota dysbiosis, with a reduced population of butyrate-producing species, abnormal inflammatory response, and micronutrient deficiency (e. g. vitamin D hypovitaminosis). Vitamin D (VitD) is involved in immune cell differentiation, gut microbiota modulation, gene transcription, and barrier integrity. Vitamin D receptor (VDR) regulates the biological actions of the active VitD (1α, 25-dihydroxyvitamin D3), and is involved in the genetic, environmental, immune, and microbial aspects of IBD. VitD deficiency is correlated with disease activity and its administration targeting a concentration of 30 ng/mL may have the potential to reduce disease activity. Moreover, VDR regulates functions of T cells and Paneth cells and modulates release of antimicrobial peptides in gut microbiota-host interactions. Meanwhile, beneficial microbial metabolites, e.g. butyrate, upregulate the VDR signaling. In this review, we summarize the clinical progress and mechanism studies on VitD /VDR related to gut microbiota modulation in IBD. We also discuss epigenetics in IBD and the probiotic regulation of VDR. Furthermore, we discuss the existing challenges and future directions. There is a lack of well-designed clinical trials exploring the appropriate dose and the influence of gender, age, ethnicity, genetics, microbiome, and metabolic disorders in IBD subtypes. To move forward, we need well-designed therapeutic studies to examine whether enhanced vitamin D will restore functions of VDR and microbiome in inhibiting chronic inflammation.

Anemia is a well-developed discipline where the concepts of precision medicine have, in part and being studied extensively. This review discusses the treatment of EPO-deficient anemia and resistance in Chronic Kidney Disease (CKD). Traditionally, erythropoietin-stimulating agents (ESA) and iron supplementation have been used to manage anemia in CKD. However, these treatments have potential risks, including cardiovascular and thromboembolic events. Newer treatments have emerged to address these risks, such as slow-release and low-dosage intravenous iron, oral iron, and erythropoietin-iron combination therapy. Another novel approach is using hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHI). This review highlights the need for precision medicine targeting genetic components of EPO-deficient anemia in CKD and discusses individual variability of genes such as the erythropoietin gene (EPO), Interleukin-β gene (IL-β), and hypoxia-inducible factor gene (HIF). Pharmacogenomics testing aims to provide targeted therapies and interventions that are tailored to the specific characteristics of an individual, optimizing treatment outcomes and minimizing resistance and adverse effects. The article concludes by suggesting the potential of receptor modification to revolutionize treatment outcome of erythropoietin deficiency anemia through integration of the mentioned approach.

The post-hoc analysis presented here aimed to address the influence of endogenous vitamin D in the immunological mechanism underlying effective mite allergoid-immunotherapy (AIT). Previously, we have shown that one subpopulation of T regulatory cells results in phenotypically identifiable as functionally potentiated and memory cells in allergic children after 12 months of this immunoactive treatment. Indeed, AIT is the only known treatment able to reshape the detrimental immune response against the allergen into a not noxious one. Besides, VD is widely considered an immunoregulatory molecule endogenously produced and exogenously provided with foods and supplements that might interact with AIT mechanism and affect its outcome. Therefore, a post-hoc analysis of the clinical and immunological data of three different cohorts of allergic patients was performed. One cohort (N=70) was on standard symptoms-controlling pharmacological treatment while the other two (N=60 and N=35, respectively) were treated with AIT for 12 months. Among the first were observed a lower mean endogenous VD level (&lt;22 ng/ml) along with worse symptoms and higher use of medications. Remarkably, the comparison between two sub-cohorts of patients with serum VD above (N=32) or below (N=28) a cut-off value set at mean value (27 ng/ml) revealed that optimal improvement of all clinical and immune parameters was achieved (as expected by effective AIT), irrespective of the VD level. Notably, the third analysis, carried out on one cohort of AIT patients also taking concomitantly VD3 as food supplement (N=19), was distinguished by uppermost overall treatment outcome (amelioration of symptoms, lowest medications requirement, and reduction of total and allergen-specific IgE) as well as the increase of allergen-specific tolerogenic memory T regulatory cells. These findings suggest that endogenous VD level affects allergy severity and allergen immunotherapy effectiveness. Also, VD3 might be investigated as an add-on supplement to get the best out of immunotherapy in VD deficient/insufficient allergic patients. The immunogenic but low-allergenic mite allergoid used as bioactive agent might have contributed to minimize allergic and highlight immunological effects described here.

Background: To determine vitamin D supplementation frequency among infants, factors that influence adherence, and reasons for discontinuation of initiated vitamin D. Methods: This cross-sectional study was conducted using a questionnaire administered to the mothers via a face-to-face interview on 560 infants aged from 1 to 24 months admitted to outpatient clinics from June to December 2017. Results: A total of 351 infants were administered vitamin D, and the rate of supplementation in the first year of life was 83%, while it was only 28% between 13 and 24 months. The rate of vitamin D supplementation was higher among infants who were exclusively formula-fed (p<.05). When the data were analyzed using logistic regression analysis, only visit family physicians seems to be a statistically significant independent variable in increasing supplementation (p<.05). Compared with family refusal, the rate of discontinuation of vitamin D by the healthcare providers was higher after the first year of life (p<.05). The rates of vitamin D discontinuation by healthcare providers, especially by nurses who considered the duration of supplementation adequate, were statistically significantly higher when compared with the fontanel closure and other reasons (p<0.05). Conclusions: The rate of vitamin D supplementation was higher among families who visited family physicians, which suggests the importance of well-baby visits. Since vitamin D supplementation was less common among exclusively breastfed infants, mothers should be educated. Healthcare professionals need further education about the importance of vitamin D supplementation and indications for discontinuation.

Background: A Few preclinical studies have shown that Knee osteoarthritis (KOA) is linked to gut microbiome dysbiosis and chronic inflammation. This pilot study was designed to look at the gut microbiome composition in KOA patients and normal individuals with or without vitamin D deficiency (VDD, serum vitamin D <30 ng/ml). Methods: This pilot study was conducted prospectively in 24 participants. The faecal samples of all the participants were taken for DNA extraction. The V3-V4 region of 16s rRNA was amplified and the library was prepared and sequenced on the Illumina Miseq platform. Results: The mean (±SD) age was 45.5 (±10.2) years with no defined co-morbidities. Of 447 total Operational Taxonomic Units (OTUs), a differential abundance of 16 nominally significant OTUs between the groups were observed. Linear discriminate analysis (LEfSe) revealed a significant difference in bacteria among the study groups. Pseudobutyrivibrio and Odoribacter were specific for VDD while Parabacteroides, Butyricimonas, and Gordonibacter were abundant in the KOA_VDD group and Peptococcus, Intestimonas, Delftia, and Oribacterium were abundant in the KOA group. About 80% of bacterial species were common among different groups and hence labeled as core bacterial species. However, the core microbiome of KOA and VDD groups were not seen in the KOA_VDD group, suggesting that these bacterial groups were affected by the interaction of the KOA and VDD factors. Conclusion: Parabacteroides, Butyricimonas, Pseudobutyrivibrio, Odoribacter, and Gordonibacter are the predominant bacteria in vitamin D deficient patients with or without KOA. Together these results indicate an association between the gut microbiome, vitamin D, and knee osteoarthritis.

The world is in the grips of the COVID-19 pandemic. Public health measures that can reduce the risk of infection and death in addition to quarantines are desperately needed. This article reviews the roles of vitamin D in reducing risk of respiratory tract infections, knowledge about the epidemiology of influenza and COVID-19, and how vitamin D supplementation might be a useful measure to reduce risk. Through several mechanisms, vitamin D can reduce risk of infections. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increase concentrations of anti-inflammatory cytokines. Several observational studies and clinical trials reported that vitamin D supplementation reduced risk of influenza, whereas others did not. Evidence supporting the role of vitamin D in reducing risk of COVID-19 includes that the outbreak occurred in winter, a time when 25-hydroxyvitamin D [25(OH)D] concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome, and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration. To reduce risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D₃ for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40–60 ng/ml (100–150 nmol/l). For treatment of people who become infected with COVID-19, higher vitamin D₃ doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.

A U.S. government health agency conducted epidemiological studies to evaluate whether exposures to drinking water contaminated with volatile organic compounds at U.S. Marine Corps Base Camp Lejeune, North Carolina, were associated with increased health risks to children and adults. These health studies required knowledge of contaminant concentrations in drinking water—at monthly intervals—delivered to family housing, barracks, and other facilities within the study area. Because concentration data were limited or unavailable during much of the period of contamination (1950s–1985), the historical reconstruction process was used to quantify estimates of monthly mean contaminant-specific concentrations. This paper integrates many efforts, reports, and papers into a synthesis of the overall approach to, and results from, a drinking-water historical reconstruction study. Results show that at the Tarawa Terrace water treatment plant (WTP) reconstructed (simulated) tetrachloroethylene (PCE) concentrations reached a maximum monthly average value of 183 micrograms per liter (ug/L) compared to a one-time maximum measured value of 215 ug/L and exceeded the U.S. Environmental Protection Agency’s current maximum contaminant level (MCL) of 5 ug/L during the period November 1957–February 1987. At the Hadnot Point WTP, reconstructed trichloroethylene (TCE) concentrations reached a maximum monthly average value of 783 ug/L compared to a one-time maximum measured value of 1,400 ug/L during the period August 1953–December 1984. The Hadnot Point WTP also provided contaminated drinking water to the Holcomb Boulevard housing area continuously prior to June 1972, when the Holcomb Boulevard WTP came on line (maximum reconstructed TCE concentration of 32 ug/L) and intermittently during the period June 1972–February 1985 (maximum reconstructed TCE concentration of 66 ug/L). Applying the historical reconstruction process to quantify contaminant-specific monthly drinking-water concentrations is advantageous for epidemiological studies when compared to using the classical exposed versus unexposed approach.

Background: Studies addressing diet quality and mental health have shown a strong association. There is limited evidence of specific vitamins essential for treating depression. This study aims to understand the impact of diet quality through supplementation of vitamins D, B6, and magnesium on depressive symptoms. Methods: Multiple datasets from the National Health and Nutrition Examination Survey 2017-March 2020 investigated the associations between vitamin D, B6, and magnesium on depression symptoms. A cross-sectional sample of adults over 20 was extracted (n=9,232). Chi-square tests and logistic regression analyses were used to investigate the associations. Results: Individuals with low doses of vitamin D were more likely to report symptoms of depression relative to those with low doses of vitamin B6 (χ²=3.9063, p=0.0481 vs. χ²=5.2071, p=0.0225). These results remained significant among those with high magnesium proportionate to high vitamin B6 (χ²=6.1272, p=0.0133 vs. χ²=5.2071, p=0.0225). Logistic regression results provided associations for all models except unadjusted vitamin D and adjusted vitamin D. Conclusions: Preventive measures could be addressed by identifying the risks of vitamin deficiencies. Further epidemiological research is needed for the individual effects of vitamin supplementation and depression symptoms.

Latest evidence revealed a possible association between Parkinson’s disease (PD) and periodontitis. We explored the causal relationship of this association through two-sample Mendelian randomization (MR) in European ancestry populations. To this end, we used openly accessible data of genome-wide association studies (GWAS) on PD and periodontitis. As instrumental variables for periodontitis, seventeen single-nucleotide polymorphisms (SNPs) from a GWAS of periodontitis (1817 periodontitis cases vs. 2215 controls) and forty-five SNPs from a GWAS of PD (20,184 cases and 397,324 controls). Eight non-overlapping SNPs of periodontitis from an additional GWAS assisted in the validation of association being studied. Multiple approaches of MR were carried-out. There was no evidence of genetic liability of periodontitis being associated with a higher risk of PD (B= -0.0003, Standard Error [SE] 0.0003, P = 0.26). The eight independent SNPs (B= -0.0000, SE 0.0001, P = 0.99) validated this outcome. We found no association of genetically primed PD towards periodontitis (B= -0.0001, SE 0.0001, P = 0.19). This MR study found no conclusive evidence to support a bidirectional causal genetic liability between PD and periodontitis. Further GWAS studies are needed to confirm the consistency of these results.

Recent studies supported a clinical association between Parkinson’s Disease (PD) and periodontitis. Hence, investigating possible protein interactions between these two conditions is of interest. In this study, we conducted a protein-protein network interaction analysis with recognized genes encoding proteins for PD and periodontitis. Genes of interest were collected via GWAS database. Then, we conducted a protein interaction analysis using STRING database, with a highest confidence cut-off of 0.9. Our protein network casted a comprehensive analysis of potential protein-protein interactions between PD and periodontitis. This analysis may underpin valuable information for new candidate molecular mechanisms between PD and periodontitis and may serve new potential targets for research purposes. These results should be carefully interpreted giving the limitations of this approach.

Background: The immunomodulatory role of 1,25-Dihydroxy vitamin D3 (1,25(OH)2D3) is exerted through its interaction with the Vitamin D receptor (VDR) present on pancreatic and immune cells. While a deficiency in Vitamin D has been linked to Type 1 Diabetes Mellitus (T1DM), the exact molecular mechanism driving this down-regulation in T1DM is yet to be fully understood. This study aimed to decipher differences in the expression of genes associated with Vitamin D metabolism in T1DM patients and to ascertain if there is a correlation between serum 1,25(OH)2D3 levels and the expression of these genes. We also sought to understand the influence of specific microRNAs (miRNAs) on the expression of Vitamin D metabolism genes in peripheral blood mononuclear cells (PBMCs) of T1DM patients. Furthermore, the study delved into the potential implications of altered Vitamin D metabolism genes and miRNAs on autoimmune processes. Methods: Utilizing real-time PCR, we assessed the expression profiles of genes encoding for 1-hydroxylases (CYP27B1) and 24-hydroxylases (CYP24A1), as well as related miRNAs, in PBMCs from 30 T1DM patients and 23 healthy controls. ELISA tests facilitated the measurement of 1,25(OH)2D3, GAD65, and IA-2 levels. Results: Our findings showcased down-regulated CYP27B1 mRNA levels, while CYP24A1 expression remained stable compared to healthy subjects (CYP27B1, p = 0.0005; CYP24A1, p = 0.205, respectively). In T1DM patients, the levels of has-miR-216b-5p were found to be increased, while the levels of has-miR-21-5p were decreased in comparison to the control group. Notably, no correlation was identified between the expression of CYP27B1 in T1DM patients and the levels of has-miR-216b-5p, has-miR-21-5p, and 1,25(OH)2D3. A significant negative correlation was identified between CYP27B1 mRNA levels in PBMCs of T1DM and IA2, but not with GAD65. Conclusions: The study highlights there were reduced levels of both CYP27B1 mRNA and has-miR-21-5p, along with elevated levels of has-miR-216b-5p in the PBMCs of T1DM. However, the absence of a correlation between the expression of CYP27B1, levels of has-miR-216b-5p, and the status of 1,25(OH)2D3 suggests the possible existence of other regulatory mechanisms. Additionally, the inverse relationship between IA2 autoantibodies and CYP27B1 expression in T1DM patients indicates a potential connection between this gene and the autoimmune processes inherent in T1DM.

The aim of this study was to develop a valid and reliable questionnaire to assess vitamin D-related knowledge, attitude and practice (KAP) in Iranian adults who may be at increased risk of vitamin D deficiency. This study was conducted on 527 subjects, aged ≥20 years from Public health care centers in Tehran, Iran. Based on results of literature review and in-depth interviews, the 38-item vitamin D-related KAP questionnaire with four subscale was developed: 1) general knowledge; 2) nutritional knowledge; 3) attitudes; 4) behaviors. Validity of the developed vitamin D-KAP questionnaire was assessed, utilizing face, content, and construct validity methods. Internal consistency was calculated to assess reliability of the current developed questionnaire. A total of 572 (54.1% female) adults, aged 30.2±7.9 years, participated in the study. All items were perceived as relevant and comprehendible by participants. Content validity was confirmed by the panel of experts. The internal consistency, as measured by Cronbach’s alpha coefficients, exceeded the minimum reliability standard of 0.60 for four subscales. The EFA suggested a four-factor construct and the results of the CFA indicated acceptable fit indices for the proposed model. No ceiling effects were observed except for general knowledge (1.2%). Floor effects detected were 0, 1.1, 2.4, and 8.7% for practice, attitude, general knowledge, and nutrition knowledge, respectively. General knowledge had the highest score (79.59±14.52) and nutrition knowledge, the lowest score (42.58±20.40) among the four sub-scales. Results confirm the initial validity and reliability of the vitamin D-related knowledge, attitude and practice questionnaire. Further investigations in different urban and rural population are recommended.

Background: This practice guideline was developed by the Chronic Kidney Disease (CKD) Task Force, which was composed of clinical and methodological experts. The Saudi Arabian Ministry of Health and its Health Holding Company commissioned this guideline project to support the realization of the Vision 2030's healthcare transformation pillar. Methods: The guideline synthesis was guided by the GRADE-ADOLOPMENT methodology. Results: The final adoloped guideline addressed 12 clinical questions on blood pressure management in patients with CKD through a set of recommendations and performance measures. The recommendations included antihypertensive agents in children, non-renin angiotensin system inhibition (Non-RASi) vs RASi in adults, intensive vs standard blood pressure targets, early vs late assessment for kidney replacement therapy (KRT), late vs early preparation strategy for KRT, CKD symptoms during assessment for KRT or conservative management, initiation of KRT in patients with deteriorating CKD, choice of KRT modality or conservative management in certain CKD patient groups, changing or discontinuing KRT modalities, review frequency for KRT or conservative management, and Information, education and support. Conclusions: These conditional recommendations were based on low to very low certainty of evidence that highlights the need for high-quality randomized trials comparing different antihypertensive agents in patients with CKD.

Thyroid hormones have a catabolic effect on bone homeostasis. Hence, this study aimed to evaluate serum vitamin D, calcium, and phosphate and bone marker levels and bone mineral density (BMD) among patients with different thyroid diseases. This cross-sectional study included patients with underlying thyroid diseases (n=64, hyperthyroid; n=53 euthyroid; and n=18, hypothyroid) and healthy controls (n=64). BMD was assessed using z-score and left hip and lumbar bone density (g/cm2). Results showed that the mean serum vitamin D Levels of all groups was low (<50 nmol/L). Thyroid patients had higher serum vitamin D levels than healthy controls. All groups had normal serum calcium and phosphate levels. The bone marker levels were significantly high in the hyperthyroid group and low in the hypothyroid group. The z-score for hip and spine did not significantly differ between thyroid patients and control groups. The hip bone density was remarkably low in the hyperthyroid group. In all groups, the serum vitamin D levels were below the cutoff value. However, thyroid patients had a higher serum vitamin D level than healthy controls. The carboxy terminal collagen crosslink and procollagen type I N-terminal propeptide levels were high in hyperthyroid patients and low in hypothyroid patients. Further, hyperthyroid patients had a low hip BMD.

One mechanism by which fructose could exert deleterious effect in metabolism and inflammation is via its potency vis-à-vis de Maillard reaction. We employed simulated stomach and duodenum digestion of ovalbumin to test the hypothesis that indeed AGEs are formed by fructose during simulated digestion of an ubiquitous food protein with intrinsic allergenic potential and under model physiological conditions. Methods: OVA was subjected to simulated gastric and intestinal digestion using standard models, in presence of fructose or glucose (0-100 mM). Peptide fractions were analyzed by fluorescence spectroscopy and intensity at Excitation: λ370 nm, Emission: λ 440nm. Results: AGE adducts form between fructose and OVA which can be found in peptide fractions (< 5 kDa) at times (30 min) and concentration ranges (10 mM) plausibly found in the intestines, whereas no reaction occurs with glucose. The reaction is inhibited by chlorogenic acid at concentrations compatible with those found in the gut. The reaction is inhibited by AG, a specific antiglycation agent. Conclusion: Our proof of principle study shows that fructose-AGE formation on an ubiquitous allergenic protein indeed occurs in one hour and thereby may pave the way for the study of yet another mechanism by which the excess fructose in our Western diets is contributing to disease: intestinal AGE formation, absorption and RAGE engagement.

Pulmonary hypertension (PH) is a progressive and potentially fatal complication of sickle cell disease (SCD) affecting 6-10% of adult SCD patients. Various mechanisms and theories have been evaluated to explain the pathophysiology of the disease. However, questions remain, particularly regarding the clinical heterogeneity of the disease in terms of symptoms, complications, and survival. Beyond the classical mechanisms that have been thoroughly investigated and include hemolysis, nitric oxide availability, endothelial disorders, thrombosis, and left heart failure, attention is focused nowadays on the potential role of the genes involved in such processes. Potential candidate genes are investigated through next-generation sequencing, with the TGF-β pathway being the initial target. This field of research may also provide novel targets for pharmacologic agents in the future as is already the case with idiopathic PH. The collection and processing of data and samples from multiple centers can yield safe results that will allow a better understanding of SCD-related PH as a part of the disease’s clinical spectrum. The following review attempts to capture the most recent findings of studies on gene polymorphisms that have been associated with PH in SCD patients.

Coronavirus disease (COVID-19) is an infectious disease caused by a new virus which causes respiratory illness. Older adults and people who have previous chronic medical conditions are at higher risk for more serious complications from COVID-19.Hypovitaminosis D is attributed to the increased risk of lung injury and acute respiratory distress syndrome (ARDS) as well as diabetes, Cardiovascular event and associated comorbidities, which are the main causes of severe clinical problem in COVID-19 patients. Considering the protective role of vitamin D through modulating the innate and adaptive immune system as well as inhibition of Renin Angiotensin System (RAS), vitamin D supplementation might boost the immune system of COVID-19 patients and reduce severity of the disease in vitamin D deficient individuals.

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder characterized by renal tubular cystic dilatations. The cysts can develop anywhere along the nephron and over time the cystic dilatation lead to kidney enlargement. On the other hand, the cysts begin to reduce the number of functional nephrons as a consequence of cystic expansion that further contributes to the decline in renal function over the years. The pressure exerted by the dilated cysts lead to compensatory mechanisms that further contribute to the decline in renal function. These structural changes are responsible of glomerular hyperfiltration states, albuminuria, proteinuria, and haematuria. However, the presentation of ADPKD varies in children from a completely asymptomatic child with incidental ultrasound detection of cysts to a rapidly progressive disease. There have been reports of early onset of ADPKD in children younger than 2 years that showed a more rapid decline in renal function. ADPKD is caused by mutation in PKD1 and PKD2 genes. Today, the PKD1 gene mutation seems to account for up to 85% of the cases worldwide, and it is associated with worse renal outcomes. Individuals with PKD2 gene mutation seem to present a milder form of the disease, with a more delayed onset of end stage kidney disease. The cardinal sign of ADPKD is the presence of renal cysts during renal ultrasound. The current guidelines provide the clinicians the recommendations for genetic testing in children with a positive family history. Given that the vast majority of children with ADPKD present with normal or supra normal kidney function we explored the glomerular filtration rates dynamics and the renal ultrasound adjusted percentiles. 14 out of 16 patients had kidney percentile over 90%. The gene mutations were equally distributed among our cohort. In addition, we compared the modified Schwartz formula to the quadratic equation after adjusting the serum creatinine measurements. It seems that even though children with ADPKD have enlarged kidneys, the renal function is more likely normal or near normal when the quadratic estimation of glomerular filtration rate is used (qGFR tended to be lower, 111.95 ± 12.43 ml/min/1.73m2 compared to Schwartz eGFR 126.28 ± 33.07ml/min/1.73m2, p=0.14). Also, when the quadratic equation was employed, not even a patient reached the glomerular hyperfiltration thresholds. The quadratic formula showed that glomerular filtration rates are linear or slightly decreasing after 1-year of follow-up (Quadratic ΔeGFR=0.32±5.78ml/min/1.73m2) as opposed to Schwartz formula that can falsely classify children in a hyperfiltration state ΔeGFR=7.51±19.46ml/min/1.73m2), p=0.019.

Treatment with calcitriol, the hormonal form of vitamin D, has shown beneficial effects in ex-perimental models of acute lung injury. In this study we aimed to analyze the associations be-tween calcitriol supplementation and the risk of SARS-CoV2 infection or COVID-19 mortality. Individuals ≥18 years old living in Catalonia and supplemented with calcitriol from April 2019 to February 2020 were compared with propensity score matched controls. Outcome variables were SARS-CoV2 infection, severe COVID-19 and COVID-19 mortality. Associations between calcitriol supplementation and outcome variables were analyzed using multivariable Cox proportional regression. A total of 8076 patients were identified as being on calcitriol treatment. Advanced chronic kidney disease and hypoparathyroidism were the most frequent reasons for calcitriol supplementation in our population. Calcitriol use was associated with reduced risk of SARS-CoV2 infection (HR 0.78 [CI 95% 0.64-0.94], p=0.010), reduced risk of severe COVID-19 and reduced COVID-19 mortality (HR 0.57 (CI 95% 0.41-0.80), p=0.001) in patients with advanced chronic kidney disease. In addition, an inverse association between mean daily calcitriol dose and COVID-19 severity or mortality was observed in treated patients, independently of renal function. Our findings point out that patients with advanced chronic kidney disease could benefit from calcitriol supplementation during the COVID-19 pandemic.

The main characteristic of polycystic kidney disease is the development of multiple fluid filled renal cysts. The discovery of mislocated Na,K-ATPase in the apical membrane of cyst lining epithelia alluded to a reversal of polarity as a possible explanation to the fluid secretion. The topic of apical Na,K-ATPase in cysts remains controversial. We investigated the localization of the Na,K-ATPase and assessed the apical-basolateral polarization of cyst lining epithelia by means of immunohistochemistry in kidney tissue from six polycystic kidney disease patients undergoing nephrectomy. The Na,K-ATPase α1 subunit was conventionally situated in the basolateral membrane of all immunoreactive cysts. Proteins of the Crumbs and partitioning defective (Par) complexes were localized to the apical membrane domain in cyst epithelial cells. The apical t-SNARE protein Syntaxin-3 also immunolocalized to the apical domain of cyst lining epithelial cells. Proteins of the basolateral Scribble complex immunolocalized to the basolateral domain of cysts. Furthermore, we confirmed that cysts can originate from virtually any tubular segment with preserved polarity. In conclusion, we find no evidence of a reversal in apical-basolateral polarity in cyst lining epithelia in polycystic kidney disease.

Most studies on vaccines of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have focused on antibody, but cellular immunities are also critical. We aimed to evaluate the immune reactions of hemodialysis (HD) patients after the administration of the booster dose from the perspective of both humoral and cellular immunities. Hemodialysis patients (HD group) and age- and sex-matched non-dialysis individuals (control group) receiving three doses of BNT162b2 vaccine were measured for anti-SARS-CoV-2 immunoglobulin (IgG) and T-SPOTⓇ.COVID test (T-SPOT) before, 3 weeks, and 3 months after the booster dose. The HD group had significantly higher SARS-CoV-2 IgG levels 3 weeks and 3 months after the booster dose than the control group, although both groups had no difference in SARS-CoV-2 IgG levels before the booster dose. Moreover, the HD group had significantly higher T-SPOT levels before and 3 weeks after the booster dose than the control group, but the difference was not significantly different 3 months after the booster dose. Furthermore, the incidence rates of local and systemic adverse reactions were significantly higher in the HD group than in the control group. HD patients obtained higher SARS-CoV-2 IgG levels and SARS-COV-2-specific T-cell responses after the booster dose than control.

The aim of this study of patients with chronic kidney disease (CKD) is to assess the safety of daily consumption of walnuts on the physiological levels of phosphorous, potassium, parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF23), and to assess the short-term benefits of this intervention on risk factors associated with cardiovascular events. This led us to perform a prospective, randomized, cross-over, pilot clinical trial examined 13 patients with chronic kidney disease (CKD). Subjects were randomly assigned to a diet of 30 g of walnuts per day or the control diet. After 30 days, each group was given a 30-day washout period, and then switched to the alternate diet for 30 days. Urinary and serum levels of phosphorous and potassium, multiple vascular risk factors, and urinary inositol phosphates (InsPs) were measured at baseline and at the end of the intervention period. Our results showed that the walnut dietary supplement led to reduced blood pressure, LDL cholesterol, and serum albumin, but had no effect on the physiological levels of phosphorous, potassium, PTH, and FGF23. This is the first report to show that daily consumption of walnuts by patients with CKD does not alter their physiological levels of phosphorous, potassium, PTH, and FGF23. Consequently, this dietary supplement may prevent cardiovascular events in patients with CKD.

Background: Hypovitaminosis D is a public health problem due to its implications for various diseases. Vitamin D has numerous functions, such as modulating the metabolism of some cellular tissues, and is expressed through the VDR gene that may influence gene expression modulation, which plays an important role in vitamin D metabolism. Objective: To evaluate the effect of the genotypes of single nucleotide polymorphism (SNP) BsmI of the vitamin D receptor (VDR) gene on VDR, SOD2, and CYP24A1 gene expression in individuals with low serum vitamin D levels. Methods: This was a cross-sectional analytical study. Individuals were invited to participate and, after signing the informed consent form, answered a structured questionnaire with identification data. Blood was collected for biochemical analysis, and vitamin D was measured by chemiluminescence; BsmI polymorphism was determined using real-time polymerase chain reaction (PCR) assays with TaqMan allelic discrimination, and gene expression was conducted by qRT-PCR using QuantiFast SYBR® Green PCR Master Mix. Data were analyzed using the SPSS 20.0 software, and differences were considered significant at p&lt;0.05. Results: 98 individuals with vitamin D ≤20 ng/dL were evaluated, and the SNP BsmI of the VDR gene showed CYP24A1 overexpression and low SOD2 expression. Conclusion: SNP Bsm I of the VDR gene can modulate the expression of the genes evaluated without interfering with serum levels.

Vitamin D has previously been quantified in some plants and algae, particularly in leaves of the Solanaceae family. We measured the vitamin D content of Australian native food plants and Australian-grown edible seaweed. Using liquid chromatography with triple quadrupole mass spectrometry, 13 samples (including leaf, fruit and seed) were analysed in duplicate for vitamin D₂, vitamin D₃, 25-hydroxyvitamin D₂ and 25-hydroxyvitamin D₃. Five samples contained vitamin D₂: raw wattleseed (Acacia victoriae) (0.03 µg/100 g dry weight (DW)); fresh and dried lemon myrtle (Backhousia citriodora) leaves (0.03 and 0.24 µg/100 g DW, respectively); dried leaves and berries of Tasmanian mountain pepper (Tasmannia lanceolata) (0.67 and 0.05 µg/100 g DW, respectively). Fresh kombu (Lessonia corrugata) contained vitamin D₃ (0.01 µg/100 g DW). Detected amounts were low; however, it is possible that exposure to ultraviolet radiation may increase the vitamin D content of plants and algae if vitamin D precursors are present.

The Vitamin D Receptor (VDR) mediates the actions of vitamin D, which has important roles in bone homeostasis, growth/differentiation of cells, immune functions and reduction of inflammation. Emerging evidences suggest that epigenetic modifications of the VDR gene, particularly DNA methylation, may contribute to the onset and progression of many human disorders. This review aims to summarize the available information on the role of VDR methylation signatures in different pathological contexts, including autoimmune diseases, infectious diseases, cancer and others. The reversible nature of DNA methylation could enable the development of therapeutic strategies, offering new avenues for the management of these worldwide diseases.

It is widely known that vitamin D receptors have been found in neurons and glial cells and their highest expression is in the hippocampus, hypothalamus, thalamus and subcortical grey nuclei, and substantia nigra. The vitamin D helps the regulation of neurotrophin, neural differentiation and maturation, through the control operation of growing factors synthesis (ie NGF and GDNF), the trafficking of the septo-hyppocampal pathway, and the control of the synthesis process of different neuromodulators (such as Ach, DA, and GABA). Based on these assumptions, we have written this review in order to summarize the potential role of vitamin D in neurological pathologies. The work could be titanic, and might result very fuzzy and even incoherent, if we would not have conjectured to taper our first intentions and devoted our interests towards three mainstreams: demyelinating pathologies, vascular syndromes and neurodegeneration. Due to the lack of effective therapeutic options, a part from the disease modifying strategies, the role of different risk factors should be investigated in neurology, as far as their correction may lead to the improvement of the cerebral conditions. We have explored the relationships between the gene-environmental influence and long term vitamin D deficiency, as a risk factor for the development of different types of neurological disorders, along with the role and the rationale of therapeutic trials with vitamin D implementation.

D-type cyclins encode G1/S cell cycle checkpoint proteins, that play a crucial role in defining cell cycle exit and progression. Precise control of cell cycle exit is vital during embryonic development, with defects in the pathways regulating intracellular D-type cyclins resulting in abnormal initiation of stem cell differentiation in a variety of different organ systems. Furthermore, stabilisation of D-type cyclins is observed in a wide range of disorders characterised by cellular over-proliferation, including cancers and overgrowth disorders. In this review, we will summarise and compare the roles played by each D-type cyclin during development and provide examples of how their intracellular dysregulation can be an underlying cause of disease.

Background/Objectives: Vitamin B12 deficiency can cause variable symptoms, which may be irreversible if not diagnosed and treated in a timely manner. We aimed to develop a widely accepted expert consensus to guide the practice of diagnosing and treating B12 deficiency. Methods: We conducted a scoping review of the literature published in PubMed since January 2003. Data were used to design a two-round Delphi survey to study the level of consensus among 42 experts. Results: The panelists agreed on the need for educational and organizational changes in the current medical practices for diagnosing and treating B12 deficiency. Recognition of clinical symptoms should receive the highest priority in establishing the diagnosis. There is agreement that the serum B12 concentration is useful as a screening marker, whereas methylmalonic acid or homocysteine can support the diagnosis. Patient lifestyle, disease history and medications can provide clues to the cause of B12 deficiency. Regardless of the cause of the deficiency, initial treatment with parenteral B12 was regarded as the first choice for patients with acute and severe manifestations of B12 deficiency. The use of high-dose oral B12 at different frequencies may be considered for long-term treatment. Prophylactic B12 supplementation should be considered for specific high-risk groups. Conclusions: There is a consensus that clinical symptoms need to receive more attention in establishing a diagnosis. B12 laboratory markers can support the diagnosis. The severity of clinical symptoms, the causes of B12 deficiency and the treatment goals govern decisions regarding the route and dose of B12 therapy.

Expression levels of Cav3.2, BKCa, and anoctamin 1 were previously found to be significantly elevated in patients with chronic kidney disease–associated pruritus (CKD-aP). On the other hand, the expression of TRPV1 was significantly reduced. We further compared CKD patients with and without CKD-aP in terms of the expression levels of several ion channels in the skin, including in peripheral nerve endings。Based on CKD-aP severity, subjects were divided into two groups: non-CKD-aP (no or slight pruritus; n = 16) and CKD-aP (mild, moderate, or severe pruritus; n = 16). Skin samples were obtained from the forearm or elbow during arteriovenous fistula surgery. We used quantitative real-time polymerase chain reaction to measure the skin expression levels of the following ion channels in the skin: Nav1.7, Kv7.2, TREK1, HCN2, TrkA, and Piezo2.　RT-PCR analyses showed that CKD-aP patients had significantly higher levels of TREK1 and Piezo2 transcripts and significantly lower levels of HCN2 transcripts than non–CKD-aP patients. No significant differences were noted between groups in the expression of Nav1.7 or TrkA. Moreover, Kv7.2 transcripts were not detected in either group. In skin samples collected from CKD-aP patients, ion channel expression patterns were altered to enhance hyperpolarization of pruriceptive neurons.

Preventing the occurrence of secondary caries serves as one of the significant issues in dental clinic, thus make it indispensable to improving the properties of conventional composite resin (CR) by developing a novel CR. In present study, two groups of experimental CRs loaded with different contents of fluoride-doped nano-zirconia fillers (25 wt% and 50 wt%) were fabricated. The surface topography, mechanical performance, fluoride release, antibacterial effect, aging property and cytotoxicity of the experimental CRs were evaluated subsequently. A uniform distribution of the F-zirconia fillers over the whole surface of resin matrix could be observed. The experimental CRs showed continuous fluoride release within 28 days, which was positively correlated with the content of F-zirconia fillers. Moreover, the amount of fluoride release increased in the acidic buffer. Addition of F-zirconia fillers could improve the color stability, wear resistance and microhardness of the experimental CRs, without reducing the flexure strength. Furtherly, the fluoride ions released continuously from the experimental CRs resulted in effective contact and antibacterial properties, while they showed no cytotoxicity. As a consequence, considerations can be made to employ this new kind of composite resin loaded with fluoride-doped nano-zirconia fillers to meet clinical requirements when the antimicrobial benefits are desired.

Despite the recent launch of Tolvaptan, the search for safer polycystic kidney disease (PKD) drugs continues. Ciclopirox, as the free acid (CPX) and its olamine salt (CPX-O) , are contained in number of commercially available topical antifungal agents. CPX is reported in the literature to possess anticancer activity in number of solid tumor cancers and hematological malignancy by several proposed mechanisms of action including chelation of iron and inhibition of iron dependent enzymes. Here, we show that CPX-O inhibited in vitro cystogenesis of primary human cyst epithelial cells cultured in 3D collagen matrix. To determine if CPX-O inhibits PKD progression, we treated PKD mice with a low dose of 10 mg/kg CPX-O by daily intraperitoneal injections from day 21 to day 49 post- partum. CPX-O reduced the kidney to body weight ratio of the PKD mice. This was associated with decreased cell proliferation decrease cystic area and improved renal function. We found that ferritin levels were significantly elevated in cystic kidneys of PKD mice, and that CPX-O treatment reduced renal ferritin levels and increased ferritinophagy marker, NCOA4. Our data suggest that CPX-O dose dependently induces ferritin degradation via ferritinophagy which is associated with decreased cyst growth and disease progression in PKD mice. Most importantly these data indicate that CPX-O, a drug used to treat skin infections and currently in clinical trials for cancer, has the potential to treat ADPKD.

Severe infection from the SARS-CoV-2 virus is associated with various clinical findings, including hematological manifestations. Thrombotic events or a tendency to develop thrombotic events also characterize severe COVID-19 disease and may lead to death. Vitamin D is known to have immunomodulating properties and to enhance the body defense system against invading pathogens and to have immunostimulatory properties as far as the innate immune response is concerned. The aim was to measure 25(OH)D3 levels in patients hospitalized for severe COVID-19 infection, to explore the relationship between 25(OH)D3 and outcome and to investigate the relationship between 25(OH)D3 levels, CRP, ferritin, d-dimers and fibrinogen levels in this cohort. In a cohort of 88 patients hospitalized for severe infection from the SARS-CoV-2 virus and a control group matched for age and sex the levels of 25(OH)D3 were measured. In the same cohort CRP, ferritin, d-dimer and fibrinogen levels were also analyzed. Levels of 25(OH)D3 were 17.36±8.80 ng/ml (mean±SD) as compared with 24.34±10.34 ng/ml, in patients with severe SARS-CoV-2 infection and the control group, respectively, p<0.001 (Student’s t test). The levels of 25(OH)D3 were found to be significantly related to outcome, i.e. survival as opposed to non-survival, as more patients with 25(OH)D3 deficiency (0-10 ng/ml) and insufficiency (10-20 ng/ml) had a fatal outcome as compared with those with vitamin D sufficiency, p<0.001, chi-square test, p<0.001, Fischer’s exact test. Levels of 25(OH)D3 were inversely related to CRP, ferritin, d-dimer and fibrinogen levels, p<0.001, linear regression analysis, beta coefficient of variation, -0.176, -0,160, -0.178, -0.158, respectively. Vitamin D deficiency observed in severe SARS-CoV-2 infection was related to the disease outcome. Increased ferritin levels, and increased thrombotic markers, namely d-dimer and fibrinogen levels were observed in the patients and their concentration was also inversely related to vitamin D. We showed that vitamin D levels were low in hospitalized patients with severe SARS-CoV-2 infection and also inversely related to CRP, ferritin, d-dimer and fibrinogen concentration. It is proposed that vitamin D levels may be an index of severity in the context of SARS-CoV-2 infection.

Appropriate supplementation of vitamin D can affect infections, allergy, and mental and behavioral development. This study aimed to assess the effectiveness of monitored vitamin D supplementation in a population of preterm infants. 109 preterm infants (24 0/7–32 6/7 weeks of gestation) were randomized to receive 500 IU vitamin D standard therapy (n=55; approximately 800-1000 IU from combined sources) or monitored therapy (n=54; with an option of dose modification). 25(OH)D concentrations were measured at birth, 4 weeks of age, and 35, 40, and 52±2 weeks of post-conceptional age (PCA). Vitamin D supplementation was discontinued in 23% of infants subjected to standard treatment due to increased potentially toxic 25(OH)D concentrations (&gt;90 ng/mL) at 40 weeks of PCA. A significantly higher infants’ percentage in the monitored group had safe vitamin D levels (20–80 ng/mL) at 52 weeks of PCA (p=0.017). We observed increased vitamin D levels and abnormal ultrasound findings in five infants. Biochemical markers of vitamin D toxicity were observed in two patients at 52 weeks of PCA in the control group. Inadequate and excessive amounts of vitamin D can lead to serious health problems. Supplementation with 800–1000 IU of vitamin D prevents deficiency and should be monitored to avoid overdose.

The role of vitamin D in the prevention and treatment of non-skeletal health issues has received significant media and research attention in recent years. Costs associated with clinical management of low vitamin D (LVD) have increased exponentially. However, no clear evidence supports vitamin D screening to improve health outcomes. Authoritative bodies and professional societies recommend against population-wide vitamin D screening in community-dwelling adults who are asymptomatic or at low risk of LVD. In order to assess patterns of physician management of LVD in this conflicting environment, we conducted a scoping review of three electronic databases and gray literature. Thirty-eight records met inclusion criteria and were summarized in an evidence table. Results from seven countries showed a consistent increase in vitamin D lab tests and related costs. Many vitamin D testing patterns reflected screening rather than targeted testing for individuals at high risk of vitamin D deficiency or insufficiency. Interventions aimed at managing inappropriate clinical practices related to LVD were effective in the short term. Variability and controversy were pervasive in many aspects of vitamin D management, shining light on physician practices in the face of uncertainty. Future research is needed is needed to inform better clinical guidelines and to assess implementation practices that encourage evidence-based management of LVD in adult populations.

Background - Chronic kidney disease with unknown aetiology (CKDu) is a progressing disease which is affecting many Sri Lankans’ yearly, this disease is slow progressive, irreversible and asymptomatic disease. Patients suffering from CKDu over the past two decades have been evaluated using the estimated glomerular filtration rate (e-GFR). This is the standard test performed under WHO guidelines to investigate and grade the CKDu, and this creatinine clearance is measured in this in order to grade the patient. Backache has been a common symptom presented in most of the chronic kidney disease patients (CKD), patients with CKDu are liable to get backache due to the renal failure that takes place (Jayathilake et al., 2013; Redmon et al., 2016). Objective – To detect a correlation between serum creatinine values and level of backache presented in the patient. Method -Using an interview based questionnaire to assess patients’ body condition and the degree of backache is assessed, 59 patients were part of the study for a period of five months and had an average age of 60.3 years. The questionnaire answers are scaled into four main types of backache from the least to the most painful based on the pain scale adapted from Kapkia. Serum creatinine is measured using an automated analyzer which is measured using Jaffe’s reaction. Using Pearson R correlation, the relationship was determined between serum creatinine and backache (Kafkia et al., 2011). Results – The results were obtained for 58 patients (n=58), where the mean backache score was 2.30 and mean serum creatinine value 2.77. The Pearson R value obtained was 0.01 which is indicating almost no relationship between backache and serum creatinine. Patients with stage 3 kidney disease (n=14) had an average E-GFR of 38.0, stage 4 (n=38) with 22.3 and stage 5 (n=6) with 14.0. Conclusion – Backache can be used an indicator of CKDu since it is presented in most patients’ suffering from the disease but unable to be used to determine the stage of CKDu suffered by the patient due to the external causes that leads to backache. Several predisposing factors such as temperature, water source and agricultural activity can influence the backache.