Anemia of Chronic Kidney Disease-A Narrative Review of Its Pathophysiology, Diagnosis, and Management.

Anemia is one of the most common chronic kidney disease (CKD) complications. It negatively affects patients' quality of life and clinical outcomes. The pathophysiology of anemia in CKD involves the interplay of various factors such as erythropoietin (EPO) deficiency, iron dysregulation, chronic inflammation, bone marrow dysfunction, and nutritional deficiencies. Despite recent advances in understanding this condition, anemia still remains a serious clinical challenge in population of patients with CKD. Several guidelines have been published with the aim to systematize the diagnostic approach and treatment of anemia; however, due to emerging data, many recommendations vary between publications. Recent studies indicate a potential of novel biomarkers to evaluate anemia and related conditions such as iron deficiency, which is often present in CKD patients. Our article aims to summarize the pathophysiology of anemia in CKD, as well as the diagnosis and management of this condition, including novel therapeutic approaches such as hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHI). Understanding these complex subjects is crucial for a targeted approach to diagnose and treat patients with anemia in CKD effectively.

Influence of Metabolic Dysregulation in the Management of Depressive Disorder-Narrative Review.

Depressive disorders are heterogeneous in nature, and their global reach makes them the cause of suffering for a million individuals worldwide. Standard treatment does not work for one in three people, and side effects can significantly reduce the quality of life. A multidisciplinary approach allows for a broader insight into the nature of the disease, given its complex etiology. One of its elements is the hypothesis of inflammation, which also accompanies obesity-related disease. Obesity and depression interact, causing many researchers to develop new non-pharmacological treatment methods for both diseases. One suggestion is physical exercises that have great potential to be used in clinical practice. They can exert changes on the central nervous system and thus modulate mood. Another is diet, which concentrates on active molecules that also affect the central nervous system (CNS). There is an urgent need to create appropriate criteria and recommendations that systematize existing knowledge and allow it to be used in practice. There is an urgent need to create appropriate criteria and recommendations that systematize existing knowledge and allow it to be used in practice.

Exploring the Significance of Gut Microbiota in Diabetes Pathogenesis and Management-A Narrative Review.

Type 2 diabetes is a disease with significant health consequences for the individual. Currently, new mechanisms and therapeutic approaches that may affect this disease are being sought. One of them is the association of type 2 diabetes with microbiota. Through the enteric nervous system and the gut-microbiota axis, the microbiota affects the functioning of the body. It has been proven to have a real impact on influencing glucose and lipid metabolism and insulin sensitivity. With dysbiosis, there is increased bacterial translocation through the disrupted intestinal barrier and increased inflammation in the body. In diabetes, the microbiota's composition is altered with, for example, a more abundant class of Betaproteobacteria. The consequences of these disorders are linked to mechanisms involving short-chain fatty acids, branched-chain amino acids, and bacterial lipopolysaccharide, among others. Interventions focusing on the gut microbiota are gaining traction as a promising approach to diabetes management. Studies are currently being conducted on the effects of the supply of probiotics and prebiotics, as well as fecal microbiota transplantation, on the course of diabetes. Further research will allow us to fully develop our knowledge on the subject and possibly best treat and prevent type 2 diabetes.

Selenium as a Modulator of Redox Reactions in the Prevention and Treatment of Cardiovascular Diseases.

Cardiovascular diseases stand as the predominant global cause of mortality, exerting a profound impact on both life expectancy and its quality. Given their immense public health burden, extensive efforts have been dedicated to comprehending the underlying mechanisms and developing strategies for prevention and treatment. Selenium, a crucial participant in redox reactions, emerges as a notable factor in maintaining myocardial cell homeostasis and influencing the progression of cardiovascular disorders. Some disorders, such as Keshan disease, are directly linked with its environmental deficiency. Nevertheless, the precise extent of its impact on the cardiovascular system remains unclear, marked by contradictory findings in the existing literature. High selenium levels have been associated with an increased risk of developing hypertension, while lower concentrations have been linked to heart failure and atrial fibrillation. Although some trials have shown its potential effectiveness in specific groups of patients, large cohort supplementation attempts have generally yielded unsatisfactory outcomes. Consequently, there persists a significant need for further research aimed at delineating specific patient cohorts and groups of diseases that would benefit from selenium supplementation.

Role of Uremic Toxins, Oxidative Stress, and Renal Fibrosis in Chronic Kidney Disease.

Affecting millions of people worldwide, chronic kidney disease is a serious medical problem. It results in a decrease in glomerular filtration rate below 60 mL/min/1.73 m, albuminuria, abnormalities in urine sediment and pathologies detected by imaging studies lasting a minimum of 3 months. Patients with CKD develop uremia, and as a result of the accumulation of uremic toxins in the body, patients can be expected to suffer from a number of medical consequences such as progression of CKD with renal fibrosis, development of atherosclerosis or increased incidence of cardiovascular events. Another key element in the pathogenesis of CKD is oxidative stress, resulting from an imbalance between the production of antioxidants and the production of reactive oxygen species. Oxidative stress contributes to damage to cellular proteins, lipids and DNA and increases inflammation, perpetuating kidney dysfunction. Additionally, renal fibrogenesis involving the accumulation of fibrous tissue in the kidneys occurs. In our review, we also included examples of forms of therapy for CKD. To improve the condition of CKD patients, pharmacotherapy can be used, as described in our review. Among the drugs that improve the prognosis of patients with CKD, we can include: GLP-1 analogues, SGLT2 inhibitors, Finerenone monoclonal antibody-Canakinumab and Sacubitril/Valsartan.

Unveiling Selected Influences on Chronic Kidney Disease Development and Progression.

Currently, more and more people are suffering from chronic kidney disease (CKD). It is estimated that CKD affects over 10% of the population worldwide. This is a significant issue, as the kidneys largely contribute to maintaining homeostasis by, among other things, regulating blood pressure, the pH of blood, and the water-electrolyte balance and by eliminating unnecessary metabolic waste products from blood. What is more, this disease does not show any specific symptoms at the beginning. The development of CKD is predisposed by certain conditions, such as diabetes mellitus or hypertension. However, these disorders are not the only factors promoting the onset and progression of CKD. The primary purpose of this review is to examine renin-angiotensin-aldosterone system (RAAS) activity, transforming growth factor-ß1 (TGF-ß1), vascular calcification (VC), uremic toxins, and hypertension in the context of their impact on the occurrence and the course of CKD. We firmly believe that a deeper comprehension of the cellular and molecular mechanisms underlying CKD can lead to an enhanced understanding of the disease. In the future, this may result in the development of medications targeting specific mechanisms involved in the decline of kidney function. Our paper unveils the selected processes responsible for the deterioration of renal filtration abilities.

Broader Perspective on Atherosclerosis-Selected Risk Factors, Biomarkers, and Therapeutic Approach.

Atherosclerotic cardiovascular disease (ASCVD) stands as the leading cause of mortality worldwide. At its core lies a progressive process of atherosclerosis, influenced by multiple factors. Among them, lifestyle-related factors are highlighted, with inadequate diet being one of the foremost, alongside factors such as cigarette smoking, low physical activity, and sleep deprivation. Another substantial group of risk factors comprises comorbidities. Amongst others, conditions such as hypertension, diabetes mellitus (DM), chronic kidney disease (CKD), or familial hypercholesterolemia (FH) are included here. Extremely significant in the context of halting progression is counteracting the mentioned risk factors, including through treatment of the underlying disease. What is more, in recent years, there has been increasing attention paid to perceiving atherosclerosis as an inflammation-related disease. Consequently, efforts are directed towards exploring new anti-inflammatory medications to limit ASCVD progression. Simultaneously, research is underway to identify biomarkers capable of providing insights into the ongoing process of atherosclerotic plaque formation. The aim of this study is to provide a broader perspective on ASCVD, particularly focusing on its characteristics, traditional and novel treatment methods, and biomarkers that can facilitate its early detection.

SGLT2 Inhibitors in Kidney Diseases-A Narrative Review.

Some of the most common conditions affecting people are kidney diseases. Among them, we distinguish chronic kidney disease and acute kidney injury. Both entities pose serious health risks, so new drugs are still being sought to treat and prevent them. In recent years, such a role has begun to be assigned to sodium-glucose cotransporter-2 (SGLT2) inhibitors. They increase the amount of glucose excreted in the urine. For this reason, they are currently used as a first-line drug in type 2 diabetes mellitus. Due to their demonstrated cardioprotective effect, they are also used in heart failure treatment. As for the renal effects of SGLT2 inhibitors, they reduce intraglomerular pressure and decrease albuminuria. This results in a slower decline in glomelular filtration rate (GFR) in patients with kidney disease. In addition, these drugs have anti-inflammatory and antifibrotic effects. In the following article, we review the evidence for the effectiveness of this group of drugs in kidney disease and their nephroprotective effect. Further research is still needed, but meta-analyses indicate SGLT2 inhibitors' efficacy in kidney disease, especially the one caused by diabetes. Development of new drugs and clinical trials on specific patient subgroups will further refine their nephroprotective effects.

Diabetic Cardiomyopathy-From Basics through Diagnosis to Treatment.

Diabetic cardiomyopathy (DCM) is the development of myocardial dysfunction in patients with diabetes despite the absence of comorbidities such as hypertension, atherosclerosis or valvular defect. The cardiovascular complications of poorly controlled diabetes are very well illustrated by the U.K. Prospective Diabetes Study (UKPDS), which showed a clear association between increasing levels of glycated hemoglobin and the development of heart failure (HF). The incidence of HF in patients with diabetes is projected to increase significantly, which is why its proper diagnosis and treatment is so important. Providing appropriate therapy focusing on antidiabetic and hypolipemic treatment with the consideration of pharmacotherapy for heart failure reduces the risk of CMD and reduces the incidence of cardiovascular complications. Health-promoting changes made by patients such as a low-carbohydrate diet, regular exercise and weight reduction also appear to be important in achieving appropriate outcomes. New hope for the development of therapies for DCM is offered by novel methods using stem cells and miRNA, which, however, require more thorough research to confirm their efficacy.

Primary Electrical Heart Disease-Principles of Pathophysiology and Genetics.

Primary electrical heart diseases, often considered channelopathies, are inherited genetic abnormalities of cardiomyocyte electrical behavior carrying the risk of malignant arrhythmias leading to sudden cardiac death (SCD). Approximately 54% of sudden, unexpected deaths in individuals under the age of 35 do not exhibit signs of structural heart disease during autopsy, suggesting the potential significance of channelopathies in this group of age. Channelopathies constitute a highly heterogenous group comprising various diseases such as long QT syndrome (LQTS), short QT syndrome (SQTS), idiopathic ventricular fibrillation (IVF), Brugada syndrome (BrS), catecholaminergic polymorphic ventricular tachycardia (CPVT), and early repolarization syndromes (ERS). Although new advances in the diagnostic process of channelopathies have been made, the link between a disease and sudden cardiac death remains not fully explained. Evolving data in electrophysiology and genetic testing suggest previously described diseases as complex with multiple underlying genes and a high variety of factors associated with SCD in channelopathies. This review summarizes available, well-established information about channelopathy pathogenesis, genetic basics, and molecular aspects relative to principles of the pathophysiology of arrhythmia. In addition, general information about diagnostic approaches and management is presented. Analyzing principles of channelopathies and their underlying causes improves the understanding of genetic and molecular basics that may assist general research and improve SCD prevention.

Mechanosensitive Cation Channel Piezo1 Is Involved in Renal Fibrosis Induction.

Renal fibrosis, the result of different pathological processes, impairs kidney function and architecture, and usually leads to renal failure development. Piezo1 is a mechanosensitive cation channel highly expressed in kidneys. Activation of Piezo1 by mechanical stimuli increases cations influx into the cell with slight preference of calcium ions. Two different models of Piezo1 activation are considered: force through lipid and force through filament. Expression of Piezo1 on mRNA and protein levels was confirmed within the kidney. Their capacity is increased in the fibrotic kidney. The pharmacological tools for Piezo1 research comprise selective activators of the channels (Yoda1 and Jedi1/2) as well as non-selective inhibitors (spider peptide toxin) GsMTx4. Piezo1 is hypothesized to be the upstream element responsible for the activation of integrin. This pathway (calcium/calpain2/integrin beta1) is suggested to participate in profibrotic response induced by mechanical stimuli. Administration of the Piezo1 unspecific inhibitor or activators to unilateral ureter obstruction (UUO) mice or animals with folic acid-induced fibrosis modulates extracellular matrix deposition and influences kidney function. All in all, according to the recent data Piezo1 plays an important role in kidney fibrosis development. This channel has been selected as the target for pharmacotherapy of renal fibrosis.

Associations of Dietary and Lifestyle Components with Atrial Fibrillation.

Atrial fibrillation (AF) is a prevalent cardiac arrhythmia that still remains a significant health concern, especially due to its consequences, including stroke and heart failure. This review explores the intricate interplay between AF, lifestyle choices, and dietary habits. It is particularly focused on findings from diverse studies about non-pharmacological methods of managing AF. Moreover, its purpose is to elucidate the implementation of lifestyle changes such as physical activity or proper diet choices in the integrated treatment strategy of patients with AF.

Unveiling Familial Hypercholesterolemia-Review, Cardiovascular Complications, Lipid-Lowering Treatment and Its Efficacy.

Familial hypercholesterolemia (FH) is a genetic disorder primarily transmitted in an autosomal-dominant manner. We distinguish two main forms of FH, which differ in the severity of the disease, namely homozygous familial hypercholesterolemia (HoFH) and heterozygous familial hypercholesterolemia (HeFH). The characteristic feature of this disease is a high concentration of low-density lipoprotein cholesterol (LDL-C) in the blood. However, the level may significantly vary between the two mentioned types of FH, and it is decidedly higher in HoFH. A chronically elevated concentration of LDL-C in the plasma leads to the occurrence of certain abnormalities, such as xanthomas in the tendons and skin, as well as corneal arcus. Nevertheless, a significantly more severe phenomenon is leading to the premature onset of cardiovascular disease (CVD) and its clinical implications, such as cardiac events, stroke or vascular dementia, even at a relatively young age. Due to the danger posed by this medical condition, we have investigated how both non-pharmacological and selected pharmacological treatment impact the course of FH, thereby reducing or postponing the risk of clinical manifestations of CVD. The primary objective of this review is to provide a comprehensive summary of the current understanding of FH, the effectiveness of lipid-lowering therapy in FH and to explain the anatomopathological correlation between FH and premature CVD development, with its complications.

The Role of Intestinal Microbiota and Diet as Modulating Factors in the Course of Alzheimer's and Parkinson's Diseases.

Many researchers propose manipulating microbiota to prevent and treat related diseases. The brain-gut axis is an object that remains the target of modern research, and it is not without reason that many researchers enrich it with microbiota and diet in its name. Numerous connections and mutual correlations have become the basis for seeking answers to many questions related to pathology as well as human physiology. Disorders of this homeostasis as well as dysbiosis itself accompany neurodegenerative diseases such as Alzheimer's and Parkinson's. Heavily dependent on external factors, modulation of the gut microbiome represents an opportunity to advance the treatment of neurodegenerative diseases. Probiotic interventions, synbiotic interventions, or fecal transplantation can undoubtedly support the biotherapeutic process. A special role is played by diet, which provides metabolites that directly affect the body and the microbiota. A holistic view of the human organism is therefore essential.

Liquid Biopsy: A New Avenue for the Diagnosis of Kidney Disease: Diabetic Kidney Disease, Renal Cancer, and IgA Nephropathy.

Kidney diseases are some of the most common healthcare problems. As the population of elderly individuals with concurrent health conditions continues to rise, there will be a heightened occurrence of these diseases. Due to the renal condition being one of the longevity predictors, early diagnosis of kidney dysfunction plays a crucial role. Currently, prevalent diagnostic tools include laboratory tests and kidney tissue biopsies. New technologies, particularly liquid biopsy and new detection biomarkers, hold promise for diagnosing kidney disorders. The aim of this review is to present modern diagnostic methods for kidney diseases. The paper focuses on the advances in diagnosing three common renal disorders: diabetic kidney disease, renal cancer, and immunoglobulin A nephropathy. We highlight the significance of liquid biopsy and epigenetic changes, such as DNA methylation, microRNA, piRNAs, and lncRNAs expression, or single-cell transcriptome sequencing in the assessment of kidney diseases. This review underscores the importance of early diagnosis for the effective management of kidney diseases and investigates liquid biopsy as a promising approach.

New Insights into Cardiovascular Diseases Treatment Based on Molecular Targets.

Cardiovascular diseases (CVDs) which consist of ischemic heart disease, stroke, heart failure, peripheral arterial disease, and several other cardiac and vascular conditions are one of the most common causes of death worldwide and often co-occur with diabetes mellitus and lipid disorders which worsens the prognosis and becomes a therapeutic challenge. Due to the increasing number of patients with CVDs, we need to search for new risk factors and pathophysiological changes to create new strategies for preventing, diagnosing, and treating not only CVDs but also comorbidities like diabetes mellitus and lipid disorders. As increasing amount of patients suffering from CVDs, there are many therapies which focus on new molecular targets like proprotein convertase subtilisin/kexin type 9 (PCSK9), angiopoietin-like protein 3, ATP-citrate lyase, or new technologies such as siRNA in treatment of dyslipidemia or sodium-glucose co-transporter-2 and glucagon-like peptide-1 in treatment of diabetes mellitus. Both SGLT-2 inhibitors and GLP-1 receptor agonists are used in the treatment of diabetes, however, they proved to have a beneficial effect in CVDs as well. Moreover, a significant amount of evidence has shown that exosomes seem to be associated with myocardial ischaemia and that exosome levels correlate with the severity of myocardial injury. In our work, we would like to focus on the above mechanisms. The knowledge of them allows for the appearance of new strategies of treatment among patients with CVDs.

Hepatorenal Syndrome-Novel Insights into Diagnostics and Treatment.

Hepatorenal syndrome (HRS) is a disorder associated with cirrhosis and renal impairment, with portal hypertension as its major underlying cause. Moreover, HRS is the third most common cause of acute kidney injury, thus creating a major public health concern. This review summarizes the available information on the pathophysiological implications of HRS. We discuss pathogenesis associated with HRS. Mechanisms such as dysfunction of the circulatory system, bacterial infection, inflammation, impaired renal autoregulation, circulatory, and others, which have been identified as critical pathways for development of HRS, have become easier to diagnose in recent years. Additionally, relatively recently, renal dysfunction biomarkers have been found indicating renal injury, which are involved in the pathophysiology of HRS. This review also summarizes the available information on the management of HRS, focusing on vasoconstrictive drugs, renal replacement therapy, and liver transplant together with currently being investigated novel therapies. Analyzing new discoveries for the underlying causes of this condition assists the general research to improve understanding of the mechanism of pathophysiology and thus prevention of HRS.

Molecular Processes Involved in the Shared Pathways between Cardiovascular Diseases and Diabetes.

Cardiovascular diseases and diabetes mellitus are currently among the diseases with the highest morbidity and mortality. The pathogenesis and development of these diseases remain strongly connected, along with inflammation playing a major role. Therefore, the treatment possibilities showing a positive impact on both of these diseases could be especially beneficial for patients. SGLT-2 inhibitors and GLP-1 receptor agonists present this dual effect. Moreover, the hostile composition of the gut microbiota could influence the progression of these conditions. In this review, the authors present the latest knowledge on and innovations in diabetes mellitus and CVD-with the focus on the molecular mechanisms and the role of the microbiota.

Novel Therapeutic Approaches in the Management of Chronic Kidney Disease.

Chronic kidney disease (CKD) is a progressive and incurable disease that impairs kidney function. Its prevalence is estimated to affect up to 800 million individuals within the general population, and patients with diabetes and hypertension are particularly at risk. This disorder disrupts the physiological mechanisms of the body, including water and electrolyte balance, blood pressure regulation, the excretion of toxins, and vitamin D metabolism. Consequently, patients are exposed to risks such as hyperkalemia, hyperphosphatemia, metabolic acidosis, and blood pressure abnormalities. These risks can be reduced by implementing appropriate diagnostic methods, followed by non-pharmacological (such as physical activity, dietary, and lifestyle adjustment) and pharmacological strategies after diagnosis. Selecting the appropriate diet and suitable pharmacological treatment is imperative in maintaining kidney function as long as possible. Drugs such as finerenone, canakinumab, and pentoxifylline hold promise for improved outcomes among CKD patients. When these interventions prove insufficient, renal replacement therapy becomes essential. This is particularly critical in preserving residual renal function while awaiting renal transplantation or for patients deemed ineligible for such a procedure. The aim of this study is to present the current state of knowledge and recent advances, providing novel insights into the treatment of chronic kidney disease.

Advances in Treatment of Dyslipidemia.

Dyslipidemias have emerged as prevalent disorders among patients, posing significant risks for the development and progression of cardiovascular diseases. These conditions are characterized by elevated levels of total cholesterol (TC), triglycerides (TGs), and low-density lipoprotein cholesterol (LDL-C). This review delves into the current treatment approach, focusing on equalizing these parameters while enhancing the overall quality of life for patients. Through an extensive analysis of clinical trials, we identify disorders that necessitate alternative treatment strategies, notably familial hypercholesterolemia. The primary objective of this review is to consolidate existing information concerning drugs with the potential to revolutionize dyslipidemia management significantly. Among these promising pharmaceuticals, we highlight alirocumab, bempedoic acid, antisense oligonucleotides, angiopoietin-like protein inhibitors, apolipoprotein C-III (APOC3) inhibitors, lomitapide, and cholesterol ester transfer protein (CETP) inhibitors. Our review demonstrates the pivotal roles played by each of these drugs in targeting specific parameters of lipid metabolism. We outline the future landscape of dyslipidemia treatment, envisaging a more tailored and effective therapeutic approach to address this widespread medical concern.