Pathomechanisms of Immunological Disturbances in ß-Thalassemia.

Thalassemia, a chronic disease with chronic anemia, is caused by mutations in the ß-globin gene, leading to reduced levels or complete deficiency of ß-globin chain synthesis. Patients with ß-thalassemia display variable clinical severity which ranges from asymptomatic features to severe transfusion-dependent anemia and complications in multiple organs. They not only are at increased risk of blood-borne infections resulting from multiple transfusions, but they also show enhanced susceptibility to infections as a consequence of coexistent immune deficiency. Enhanced susceptibility to infections in ß-thalassemia patients is associated with the interplay of several complex biological processes. ß-thalassemia-related abnormalities of the innate immune system include decreased levels of complement, properdin, and lysozyme, reduced absorption and phagocytic ability of polymorphonuclear neutrophils, disturbed chemotaxis, and altered intracellular metabolism processes. According to available literature data, immunological abnormalities observed in patients with thalassemia can be caused by both the disease itself as well as therapies. The most important factors promoting such alterations involve iron overload, phenotypical and functional abnormalities of immune system cells resulting from chronic inflammation oxidative stress, multiple blood transfusion, iron chelation therapy, and splenectomy. Unravelling the mechanisms underlying immune deficiency in ß-thalassemia patients may enable the designing of appropriate therapies for this group of patients.

The Impact of CKD on Uremic Toxins and Gut Microbiota.

Numerous studies have indicated that the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD) is strictly associated with the accumulation of toxic metabolites in blood and other metabolic compartments. This accumulation was suggested to be related to enhanced generation of toxins from the dysbiotic microbiome accompanied by their reduced elimination by impaired kidneys. Intestinal microbiota play a key role in the accumulation of uremic toxins due to the fact that numerous uremic solutes are generated in the process of protein fermentation by colonic microbiota. Some disease states, including CKD, are associated with the presence of dysbiosis, which can be defined as an "imbalanced intestinal microbial community with quantitative and qualitative changes in the composition and metabolic activities of the gut microbiota". The results of studies have confirmed the altered composition and functions of gut microbial community in chronic kidney disease. In the course of CKD protein-bound uremic toxins, including indoxyl sulfate, p-cresyl glucuronide, p-cresyl sulfate and indole-3-acetic acid are progressively accumulated. The presence of chronic kidney disease may be accompanied by the development of intestinal inflammation and epithelial barrier impairment leading to hastened systemic translocation of bacterial-derived uremic toxins and consequent oxidative stress injury to the kidney, cardiovascular and endocrine systems. These findings offer new therapeutic possibilities for the management of uremia, inflammation and kidney disease progression and the prevention of adverse outcomes in CKD patients. It seems that dietary interventions comprising prebiotics, probiotics, and synbiotics could pose a promising strategy in the management of uremic toxins in CKD.

Embracing the polypill as a cardiovascular therapeutic: is this the best strategy?

INTRODUCTION: Cardiovascular disease (CVD) is an important cause of mortality and morbidity worldwide. CVD morbidity and mortality are associated with significant financial costs related to hospitalization, medication, and lost productivity. The concept of the 'polypill' for the reduction of cardiovascular risk was proposed in 2000. A polypill is a fixed combination of drugs in a single tablet or capsule. The initial polypill consisted of three different classes of antihypertensive drugs (each at half dose), in addition to aspirin, a statin, and folic acid. The challenge today is to produce polypills containing drugs with established efficacy and complementary actions. Areas covered: The authors provide their expert perspectives on the polypill and consider the randomized clinical trials that have evaluated the safety, efficacy, adherence, and cost-effectiveness of polypills. Expert opinion: The polypill makes prescribing easier by reducing the need for complex treatment algorithms and dose titration. It also appears to be cost-effective. However, there are several issues that need to be addressed before the polypill can be used routinely. A single polypill formulation may not be suitable for all patients. It may be necessary to develop several types of polypill to meet the needs of different patient groups.

Impact of Vitamin D on the Cardiovascular System in Advanced Chronic Kidney Disease (CKD) and Dialysis Patients.

In patients suffering from chronic kidney disease (CKD), the prevalence of cardiovascular disease is much more common than in the general population. The role of vitamin D deficiency had been underestimated until a significant association was found between vitamin D therapy and survival benefit in haemodialysis patients. Vitamin D deficiency is present even in the early stages of chronic kidney disease. The results of experimental studies have revealed the relationship between vitamin D deficiency and impairment of cardiac contractile function, higher cardiac mass and increased myocardial collagen content. Experimental models propose that intermediate end points for the relationship between vitamin D deficiency and higher risk of cardiovascular disease comprise diminished left ventricular hypertrophy (LVH), enhanced left ventricular diastolic function, and decreased frequency of heart failure. Multiple observational studies have demonstrated an association between the use of active vitamin D therapy in patients on dialysis and with CKD and improved survival. However, there are also many studies indicating important adverse effects of such treatment. Therefore, large randomized trials are required to analyze whether supplementation of vitamin D may affect outcomes and whether it is safe to be used in CKD patients.

Hypertension - Current Natural Strategies to Lower Blood Pressure.

The prevalence of hypertension (HTN) worldwide is high and is constantly rising. HTN is considered to be a silent killer since often there are no obvious symptoms but long-term, HTN significantly increases the risk of coronary heart disease and cerebrovascular diseases. Those with diagnosed HTN or at high risk of its development, should start blood pressure (BP) lowering therapy based on natural methods including: lifestyle, regular physical activity, respiratory training, reducing body mass, lowering sodium intake with food, potassium supplementation, balanced diet enriched with herbs, reducing caffeine and alcohol intake, smoking cessation, stress avoidance and regular monitoring of the BP. This review focuses on several most common methods of natural BP lowering since it is not possible to consider all of them.

Combination drug versus monotherapy for the treatment of autosomal dominant polycystic kidney disease.

INTRODUCTION: Despite progress in the understanding of pathogenetic mechanisms of organ cyst formation in autosomal dominant polycystic kidney disease, current treatment methods are insufficient. Experimental studies and clinical trials target at inhibition of cysts development and to slowing CKD progression. AREAS COVERED: The purpose of this analysis is to overview available literature regarding treatment of ADPKD. The most important recent events concerning ADPKD treatment are: the results of TEMPO 3/4 study and the registration of tolvaptan in the treatment of patients with CKD stage I-III and rapidly progressive ADPKD by EMA. ERA-EDTA recommendations for use of tolvaptan in ADPKD of 2016 will be useful for the identification of patients with rapid progression of disease who will benefit most from treatment. Clinical trials concerning inhibitors of mTOR and SSAs have not delivered convincing evidence of their effectiveness. Usefulness of statins in ADPKD require confirmation in adults. The HALT-PKD study confirmed that inhibition of RAA system slows progression of ADPKD. EXPERT OPINION: Current treatment of ADPKD involves: the optimization of life style and combined pharmacological treatment with ACE inhibitors or angiotensin receptor blockers, statins (patients with lipid disorders and cardiovascular disease) and tolvaptan (patients with stage I-III CKD and rapidly progressive ADPKD).

Lipid-modifying effects of nutraceuticals: An evidence-based approach.

The present review provides an up-to-date summary of the findings on the lipid-lowering effects of the most important nutraceuticals and functional foods. Based on current knowledge, nutraceuticals might exert significant lipid-lowering, and their use has several advantages: A number of important questions remain to be addressed, including whether longer durations of therapy would result in a better response and the exact safety profile of nutraceuticals, especially at doses higher than those consumed in an average diet. Additionally, data regarding the effects of nutraceutical supplementation on the incidence of cardiovascular outcomes are lacking, and it is not clear whether additional lipid lowering by nutraceuticals can modify the residual cardiovascular risk that remains after statin therapy.