91 research outputs found
Stroke from A Large Left Atrial Myxoma
A 36-year-old male involved in a car accident was found to have an embolic stroke due to a left atrial myxoma. Open heart surgery was delayed 4 weeks to decrease the risk of neurologic complications from the anticoagulation required for cardiopulmonary bypass. After resection of the myxoma, intraoperative transesophageal echocardiography found severe mitral regurgitation, which was repaired
Biatrial myxoma and multiple organ infarctions combined with Leriche syndrome in a female patient
Complement C5a induces renal injury in diabetic kidney disease by disrupting mitochondrial metabolic agility
The sequelae of diabetes include microvascular complications such as diabetic kidney disease (DKD), which involves glucose-mediated renal injury associated with a disruption in mitochondrial metabolic agility, inflammation, and fibrosis. We explored the role of the innate immune complement component C5a, a potent mediator of inflammation, in the pathogenesis of DKD in clinical and experimental diabetes. Marked systemic elevation in C5a activity was demonstrated in patients with diabetes; conventional renoprotective agents did not therapeutically target this elevation. C5a and its receptor (C5aR1) were upregulated early in the disease process and prior to manifest kidney injury in several diverse rodent models of diabetes. Genetic deletion of C5aR1 in mice conferred protection against diabetes-induced renal injury. Transcriptomic profiling of kidney revealed diabetes-induced downregulation of pathways involved in mitochondrial fatty acid metabolism. Interrogation of the lipidomics signature revealed abnormal cardiolipin remodeling in diabetic kidneys, a cardinal sign of disrupted mitochondrial architecture and bioenergetics. In vivo delivery of an orally active inhibitor of C5aR1 (PMX53) reversed the phenotypic changes and normalized the renal mitochondrial fatty acid profile, cardiolipin remodeling, and citric acid cycle intermediates. In vitro exposure of human renal proximal tubular epithelial cells to C5a led to altered mitochondrial respiratory function and reactive oxygen species generation. These experiments provide evidence for a pivotal role of the C5a/C5aR1 axis in propagating renal injury in the development of DKD by disrupting mitochondrial agility, thereby establishing a new immunometabolic signaling pathway in DKD
Standardization of medium composition and agricultural waste in the production of p-hydroxybenzoic acid by Paecilomyces variotii
Higher dietary salt intake is associated with microalbuminuria, but not with retinopathy in individuals with type 1 diabetes: the EURODIAB Prospective Complications Study
Effects of glycaemic management on diabetic kidney disease
Hyperglycaemia contributes to the onset and progression of diabetic kidney disease (DKD). Observational studies have not consistently demonstrated a glucose threshold, in terms of HbA1c levels, for the onset of DKD. Tight glucose control has clearly been shown to reduce the incidence of micro- or macroalbuminuria. However, evidence is now also emerging to suggest that intensive glucose control can slow glomerular filtration rate loss and possibly progression to end stage kidney disease. Achieving tight glucose control needs to be balanced against the increasing appreciation that glucose targets for the prevention of diabetes related complications need be individualised for each patient. Recently, empagliflozin which is an oral glucose lowering agent of the sodium glucose cotransporter-2 inhibitor class has been shown to have renal protective effects. However, the magnitude of empagliflozin's reno-protective properties are over and above that expected from its glucose lowering effects and most likely largely result from mechanisms involving alterations in intra-renal haemodynamics. Liraglutide and semaglutide, both injectable glucose lowering agents which are analogues of human glucagon like peptide-1 have also been shown to reduce progression to macroalbuminuria through mechanisms that remain to be fully elucidated. Here we review the evidence from observational and interventional studies that link good glucose control with improved renal outcomes. We also briefly review the potential reno-protective effects of newer glucose lowering agents
The importance of glycaemic control in slowing the progression of diabetic kidney disease
Cardio-renal protection with empagliflozin
Cardiovascular (CV) and kidney disease are common and significant complications in people with type 2 diabetes (T2DM). CV disease is the leading cause of death, morbidly and hospitalisations for people with T2DM. Furthermore, diabetic kidney disease is a major risk factor for CV disease and is the main reason why patients need renal replacement therapy. In this perspective, we highlight the results of the recent landmark EMPA-REG OUTCOME trial which has shown that empagliflozin, a member of the sodium-glucose co-transporter 2 (SGLT-2) inhibitor class of glucose lowering medications, reduces death from CV causes, hospitalisation for heart failure and progression to end stage kidney disease in patients with T2DM and established CV disease. The SGLT2 receptor mediates high-capacity glucose uptake in the early proximal tubule, and SGLT2 inhibitors, via their ability to promote glycosuria, have been developed as glucose lowering medications. As well as having a glucose lowering effect, SGLT-2 inhibitors also reduce blood pressure, promote weight loss and reduce uric acid levels. Potential side-effects or concerns related to the use of SGLT-2 inhibitors include increased rates of urinary tract infections, genital tract infections, postural hypotension, diabetic ketoacidosis, acute kidney injury and possible increased rates of fractures. The exact mechanisms that result in empagliflozin’s dramatic CV and renal protective effects, with a very favourable safety/tolerability profile, in the EMPA-REG study remain to be fully defined. However, they are most likely distinct from the glucose lowering effects of empagliflozin. CV safety trials involving dapagliflozin and canagliflozin, members of the SGLT-2 class, are under way and the results from these studies will help to answer the question as to whether the cardio-renal benefits of empagliflozin are a class-effect or not. Without doubt, trials to investigate whether SGLT-2 inhibitors have cardio-renal protective effects in patients without diabetes will start soon
Exploration of the shared pathophysiological mechanisms of gestational diabetes and large for gestational age offspring
Gestational diabetes mellitus (GDM) and large for gestational age (LGA) offspring are two common pregnancy complications. Connections also exist between the two conditions, including mutual maternal risk factors for the conditions and an increased prevalence of LGA offspring amongst pregnancies affected by GDM. Thus, it is important to elucidate potential shared underlying mechanisms of both LGA and GDM. One potential mechanistic link relates to macronutrient metabolism. Indeed, derangement of carbohydrate and lipid metabolism is present in GDM, and maternal biomarkers of glucose and lipid control are associated with LGA neonates in such pregnancies. The aim of this paper is therefore to reflect on the existing nutritional guidelines for GDM in light of our understanding of the pathophysiological mechanisms of GDM and LGA offspring. Lifestyle modification is first line treatment for GDM, and while there is some promise that nutritional interventions may favourably impact outcomes, there is a lack of definitive evidence that changing the macronutrient composition of the diet reduces the incidence of either GDM or LGA offspring. The quality of the available evidence is a major issue, and rigorous trials are needed to inform evidence-based treatment guidelines
Potential for novel biomarkers in diabetes-associated chronic kidney disease: Epigenome, metabolome, and gut microbiome
Diabetes-associated chronic kidney disease is a pandemic issue. Despite the global increase in the number of individuals with this chronic condition together with increasing morbidity and mortality, there are currently only limited therapeutic options to slow disease progression. One of the reasons for this is that the current-day “gold standard” biomarkers lack adequate sensitivity and specificity to detect early diabetic chronic kidney disease (CKD). This review focuses on the rapidly evolving areas of epigenetics, metabolomics, and the gut microbiome as potential sources of novel biomarkers in diabetes-associated CKD and discusses their relevance to clinical practice. However, it also highlights the problems associated with many studies within these three areas—namely, the lack of adequately powered longitudinal studies, and the lack of reproducibility of results which impede biomarker development and clinical validation in this complex and susceptible population.</jats:p
- …