Role of angiotensin-converting enzyme inhibitors in reducing cardiovascular and cerebral complications in chronic kidney disease: focus perindopril

In the development of renocardial relationships in chronic kidney disease, an important role is given to the activation of the renin-angiotensin-aldosterone system (RAAS), as the main component of the progression and development of cardiovascular complications..The presented review is devoted to the analysis of modern scientific data on the effect of high RAAS activity in chronic kidney disease on the course and prognosis of cardiovascular complications, as well as the protective capabilities of angiotensin-converting enzyme inhibitors, in particular perindopril. The results of scientific research on the role of the RAAS in the progression of chronic kidney disease are summarized. Data on chronic kidney disease as a risk factor for cardiovascular and cerebral complications are presented. Attention is focused on the possibilities of prolonging the pre-dialysis period of chronic kidney disease when using angiotensin-converting enzyme inhibitors. The role of perindopril as a lipophilic angiotensin-converting enzyme inhibitor with a high affinity for tissue RAAS was emphasized in reducing cardiovascular and cerebral risk in chronic kidney disease

ОЖИРЕНИЕ И МЕТАБОЛИЧЕСКИЙ СИНДРОМ: ПАТОФИЗИОЛОГИЧЕСКАЯ РОЛЬ КИШЕЧНОЙ МИКРОБИОТЫ И ПОТЕНЦИАЛЬНЫЕ ВОЗМОЖНОСТИ АЛЬТЕРНАТИВНОЙ ТЕРАПИИ

The review presents data describing the current state of knowledge about the link between gut microbiota, obesity and metabolic syndrome. Pathophysiological role of gut microbiota in the development of obesity and metabolic syndrome is discussed. Potential of alternative therapy in controlling energy consumption and reducing the prevalence of obesity and metabolic syndrome is considered.В обзоре представлены данные, характеризующие современное состояние знаний о связи между кишечной микробиотой, ожирением и метаболическим синдромом. Обсуждается патофизиологическая роль кишечной микробиоты в развитии ожирения и метаболического синдрома. Рассматриваются потенциальные возможности альтернативной терапии для контроля потребления энергии и снижения распространённости ожирения и метаболического синдрома

Coronavirus disease 2019 (COVID-19): NETosis-associated mechanisms of progression and prospects for therapy regulating the formation of neutrophil extracellular traps (NETs)

Infectious disease COVID-19 caused by the SARS-CoV-2 coronavirus is characterized by high contagiousness, complexity of pathogenesis and unpredictability of the clinical course. In severe cases, which are especially susceptible to men, the elderly and people with underlying medical conditions such as obesity, diabetes, hypertension, cardiovascular and chronic respiratory diseases, the infection leads to respiratory failure and death due to the development of an extensive inflammatory reaction. As a result of many studies, it has been established that one of the leading causes of the severe course and death of patients with COVID-19 is the development of coagulopathy, that is, increased thrombus formation in small vessels due to excessive activity of neutrophils, which form the so-called neutrophil extracellular traps (NETs). Although NETs play a useful role in protecting their host from pathogens, their overgrowth can trigger a cascade of adverse reactions including: the production of antibodies against the host’s DNA (autoimmunization); damage to surrounding tissue; or the occurrence of thromboembolic complications. Therefore, extracellular neutrophil traps and their markers have been identified as targets for new therapeutic strategies aimed at reducing the severity of COVID-19 disease and/or mortality. This article describes the structure of NETs, as well as analyzes the molecular mechanisms that contribute to their overgeneration. In addition, the prospects for COVID-19 therapy aimed at regulating the formation of extracellular traps by creating drugs both limiting the production of NET structures and dissolving their excess amounts in the body of patients are discussed

Assessment of the clinical status and behavioral risk factors in patients with cardiovascular and other noncommunicable diseases in Russia and neighboring countries during quarantine and self-isolation

Aim. To carry out a comparative assessment of the clinical status and behavioral risk factors in patients with cardiovascular (CVD) and other noncommunicable diseases (NCDs) in Russia and neighboring countries during quarantine and selfisolation in the context of coronavirus disease 2019 (COVID-19) pandemic.Material and methods. The study involved patients from Russia, Azerbaijan, Kazakhstan, Lithuania, Kyrgyzstan. A total of 351 men and women aged 30- 69 years with one or more NCDs were included, including hypertension (HTN), coronary artery disease with or without myocardial infarction, type 2 diabetes, chronic obstructive pulmonary disease/ asthma, and cancer that were in quarantine self-isolation. To assess the clinical status and risk factors, patients underwent a questionnaire and examination. The changes in health status was assessed using the EQ-5D questionnaire.Results. During self-isolation and quarantine, 40% of patients noted a decrease and limitation of physical activity. An increase in food frequency and amount was registered in 35% of individuals. During quarantine, every third patient with HTN had hypertensive crises, and every fifth increased the doses of the drugs taken. In the examined cohort, exertional angina (30%) took second place among NCDs. In the group of Azerbaijan patients, every second had exertional angina, while in the Russian cohort — 33%, and in the Lithuanian group — every fourth patient. In general, health status deterioration among people with angina was noted in 6% of cases. In the examined group, type 2 diabetes was detected in 25% of cases. During quarantine, changes in hypoglycemic therapy were carried out in an average of 34% of patients. COVID-19 was registered in 22% of patients in the examined cohort. The largest number was found in the group from Kazakhstan — 57%, while the second place was taken by the Azerbaijan group — 40%. General condition deterioration was detected in 55% of cases in groups from Azerbaijan and Kazakhstan. In Russia, this was reported by 28,8% of patients, while in the group from Lithuania, every fourth patient noted a worsening of the health status. The lowest deterioration was registered in the Kyrgyzstan group (14%).Conclusion. During quarantine and self-isolation among patients with NCDs, a decrease in physical activity, an increase in food consumption and smoking was noted. There was health status deterioration in patients with various NCDs, primarily with CVDs, which required therapy changes. Taken together, this was reflected in general condition worsening in patients with chronic NCDs. It is obvious that the development of comprehensive preventive measures in conditions of selfisolation and quarantine is required

Association of hypertriglyceridemia with risk factors for cardiovascular and renal complications in individuals with high cardiovascular risk

Aim. To study clinical and functional manifestations of hypertriglyceridemia and its association with risk factors for cardiovascular and renal complications in individuals with high cardiovascular risk.Material and methods. The study included 272 patients (129 men and 143 women; mean age, 53,9±13,7 years) with a high cardiovascular risk, which was stratified using Systematic Coronary Risk Evaluation (SCORE) model by the presence of cardiovascular disease, and/or diabetes, and/or age ≥65 years, and/or blood pressure (BP) >180/110 mm Hg, and/or total cholesterol (TC) level >8,0 mmol/l. All study participants underwent clinical and paraclinical examination. Serum content of triglycerides (TGs) ≥1,7 mmol/L was considered hypertriglyceridemia (HTG). Depending on TG level, the entire sample was divided into 2 following subgroups: subgroup 1 (n=178) — serum triglycerides ≤1,6 mmol/l; subgroup 2 (n=94) — serum triglycerides ≥1,7 mmol/l, i.e. HTG.Results. We revealed significantly more persons with obesity (46,8%) and type 2 diabetes (28,7%) in HTG subgroup. There were 56,3% and 36,1% patients of HTG subgroup with hypertension (HTN) and coronary artery disease (CAD), respectively. A mid-high TG level (from 1,7 to 2,3 mmol/l) in the subgroup of patients with HTG was detected in 38,3% of cases. The serum content of TG from 2,3 to 5,6 mmol/l was detected in 54,2% of patients. TG level ≥5,6 mmol/l was detected in 7,5% of cases. In the subgroup of patients with HTG, high levels of systolic, diastolic and central (aortic) BP, body mass index, phosphorus, creatinine, cystatin C, estimated glomerular filtration rate (eGFR), and carotid intima-media thickness (IMT) were detected significantly more common. In the general sample, a significant direct relationship between TG concentration and cystatin C (r=0,168) and an inverse (negative) relationship with eGFR (r=-0,220) was obtained.Conclusion. Elevated serum TG levels are often observed in individuals with obesity, type 2 diabetes, hypertension and CAD. Patients with HTG had a pronounced cardiovascular and renal risk, including a significant increase in BP and carotid IMT, high levels of total cholesterol, low-density lipoprotein cholesterol, phosphorus, creatinine, cystatin C, and a decrease in eGFR. HTG was associated with an increase in serum cystatin C and a deterioration in renal nitrogen excretion

Damage of the muscle system in Covid-19

The article is devoted to the lesion of the muscular system in the new coronavirus disease - 2019. The analysis of the literature of Russian and foreign researchers on the extrapulmonary manifestations of COVID-19 is carried out. The main target of COVID-19 (CoronaVIrus Disease 2019) is the vascular endothelium. To enter cells, the virus uses a receptor - angiotensin-converting enzyme 2 (ACE2). It has been shown that up to three viruses can attach to one target. Skeletal muscles also have ACE2. In COVID-19, involvement of the muscular system in the pathological process is a predictor of a poor prognosis. In 20% of hospitalized COVID 19 patients, laboratory signs of heart muscle damage are found. The main mechanisms of muscle damage in COVID 19 include ACE2-dependent, viral load, cytokine storm, acute hypoxemia, and drug toxicity. Damage to the muscular system in COVID 19 is an additional risk factor for death. The presented work provides information on the possible pathogenetic mechanisms of the development of myopathy, as well as muscle weakness in COVID-19, occurring with an increase in blood creatine kinase

Anemia of chronic kidney disease: novel physiological approaches to therapy based on simulation of hypoxic response

Anemia is a modifiable risk factor for the progression of chronic kidney disease (CKD) and is characterized by a  decrease in the hemoglobin level, the hematocrit, and the number of circulating red blood cells. In the pre-erythropoietin era blood transfusion was a  common practice for the adequate correction of anemia in patients with CKD. However, a  recombinant human erythropoietin, that was developed and implemented into a clinical practice three decades ago, made a revolution in the renal anemia treatment. Today the management of anemia is based on the use of exogenous erythropoiesis-stimulating agents, such as erythropoietin and its analogues, as well as an oral or parenteral administration of iron. Nevertheless, despite of the high efficacy in the majority of patients this approach has a  negative side. The hemoglobin excursions, increased risk of cardiovascular complications, as well as the development of iron deficiency and chronic inflammation become additional factors in the pathogenesis of anemia associated with the renal failure. In this regard, the development of effective and safe methods of anemia management in CKD is of immediate interest. New medications based mainly on physiological approach are developed. A pharmacological activation of hypoxia-inducible factor (HIF) response is one of them. HIF is the main hormonal regulator of erythropoiesis that stimulates the production of endogenous erythropoietin. It is known that in patients with renal failure, the activation of this factor in response to hypoxia is compromised, resulting in a lack of erythropoietin production. This review covers the new mechanistic views on the hypoxic regulation of erythropoiesis and the production of erythropoietin by the kidneys, and presents the newly discovered interactions between the synthesis of erythropoietin, iron metabolism, and the chronic inflammation. Besides that, ongoing clinical trials of pharmacological HIF activators, such as FG-4592, GSK1278863, AKB-6548, BAY85-3934 are also discussed as a  new comprehensive and physiological approach for the treatment of anemia associated with CKD. Preliminary results of the clinical trials demonstrated a high efficiency of HIF activators in the treatment of renal anemia including a high tolerability, an increase in hemoglobin level and its maintenance in the target range, an increase in general capacity for iron binding and a reduction in the serum levels of both ferritin and hepcidin. However, there are some safety-related problems that include proangiogenic and adverse cardiovascular and metabolic complications, so the possibility of their development should be thoroughly studied in long-term clinical trials

BETA-BLOCKERS AND RENOPROTECTION: THE POTENTIAL OF CARVEDILOL

The review presented the importance of carvedilol using in terms of renoprotection in renal dysfunction at the pre-dialysis stage of the disease in order to reduce the risk of progression of chronic kidney diseases (CKD) and the development of cardiovascular complications. Immune and non-immune mechanisms (proteinuria, dyslipidemia, anemia, arterial hypertension) of renal dysfunction progression in patients with CKD of inflammatory and non-inflammatory origin are described. Moreover, with the slowing down of the glomerular filtration rate in CKD, the role of non-immunefactors in the development of cardiovascular complications becomes very important. In contrast to non-selective and some β1-selective beta-blockers, the use of beta-adenoblocker with vasodilating activity, in particular carvedilol, makes it possible to prevent the onset of the terminal stage ofCKD. Carvedilol, being a lipophilic beta-adrenoblocker of the third generation with alpha-blocking properties, influences the possible mechanismsof renoprotection: antihypertensive (including in combined antihypertensive therapy), anti-inflammatory, antiproliferative, anti-apoptotic, antioxidant, antiplatelet and others. Carvedilol due to the vasodilating effect softens the stress of the parietal shear, exerting a retarding action on theprogression of CKD. Carvedilol with a pronounced vasodilating effect and a long half-life significantly reduces central arterial pressure that is also animportant renoprotective mechanism in the treatment of patients with renal dysfunction. Carvedilol has an important renoprotective mechanism in CKD – inhibition of the secretion of the potent vasoconstrictor endothelin. In the metabolic syndrome, in which there is a significant risk of developing renal dysfunction, carvedilol levels the imbalance of adipokine secretion, insulin resistance, sodium and water retention, and the activation of renin-angiotensin-aldosterone and sympathoadrenal systems. Carvedilol at the early stages of CKD development shows predominantly antihypertensive action due to inhibition of the renin-angiotensin-aldosterone system activity directly in the kidneys. At the late stage of the disease, the drug is able to retain residual kidney function. That is, carvedilol can be used at all stages of CKD development, regardless of the etiology of kidney damage

Focal segmental glomerulosclerosis: current status of the problem

One of the most prognostically unfavorable variants of glomerulopathy is focal segmental glomerulosclerosis (FSHC), which is detected by nephrobiopsy in 5-20% of patients with nephrotic syndrome (NS) and in 15% of adult patients with chronic glomerulonephritis. FSGS recurs in a transplanted kidney in 30-50% of patients. Among adult patients with FSH, men predominate. A poor prognosis of FSHC is explained by the heterogeneity of the disease and is exacerbated by a poor response to treatment. According to current data, FSGS is characterized by sclerosis of the mesangial matrix, hyalinosis, damage to capillaries, an increase in foam cells and their adhesion between the glomerular bundle and the Bowman capsule. In 2004, the following histological variants of FSGS were proposed: apical, perichillary, collaborating, cellular and classical. Each histological variant of FSGS differs in etiology, response to treatment, and prognosis. The clinical diagnosis of primary FSHC should be based on the exclusion of secondary causes of the disease. Focal sclerotic changes in the glomeruli can be caused by various factors and occur in various conditions, including the existing kidney pathology. According to international recommendations for the treatment of FSHS, one should focus on the amount of daily proteinuria. For patients with FSHS without pronounced proteinuria, the use of angiotensin converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor blockers (ARBs) is recommended. In FSGS and NS, immunosuppressive therapy is used along with ACE inhibitors or ARB II. For adult patients, glucocorticoids (HA) are prescribed daily in a single dose at a dose of 1 mg / kg per day, the maximum dose is 80 mg with a daily intake and 120 mg with an alternating regimen. Resistance to HA is detected in the absence of effect after 16 weeks. In the presence of contraindications or intolerance to HA, calcineurin inhibitors are used. The recommended initial dose of cyclosporine is 2 mg / kg / day, taken twice a day with a gradual increase to 3.5-4 mg / kg / day. The duration of therapy with satisfactory tolerance to cyclosporine is more than six months. After achieving complete remission, the dose of cyclosporin is gradually reduced by 0.5 mg / kg / day to the minimum effective dose (1.5-2 mg / kg / day) and such maintenance therapy is carried out for 1-2 years. A treatment option is possible using lower doses of HA and cyclosporine, or a combination of mycophenolate mofetil with a high dose of dexamethasone

EFFECT OF RENAL DYSFUNCTION ON THE CARDIACVASCULAR SYSTEM. THE POSSIBILI TIES OF EARLY DIAGNOSIS OF THE RENAL DYSFUNCTION

The review is devoted to the discussion of modern concepts of the role of renal dysfunction in the development of chronic myocardial dysfunction in the context of cardio-renal syndrome (RVC) type 4. At the beginning of the review, the definition of cattle is given, general questions of pathogenesis and diagnosis of the disease are addressed. It is indicated that in patients with the initial stage of CKD, cardiovascular disorders are already registered which in the late stages of development of renal dysfunction are the leading causes of death and the true severity of the disease in patients with renal dysfunction is associated with an increased risk of cardiovascular events, rather than an achievement terminal renal failure and requiring renal replacement therapy. The progression of renal pathology leads to damage to the heart through various mechanisms and factors, both traditional and non-traditional, some of which, at the culmination of the renal continuum, are the result of the dialysis procedure itself in patients with terminal renal dysfunction. Mechanisms for the development of congestive heart failure in type 4 cattle include pressure overload (arterial hypertension) and volume (anemia, edematous syndrome), which increase in proportion to the decrease in renal function. Increase in blood pressure, changes in intracardial hemodynamics, deterioration of arterial compliance contribute to the acceleration of cardiovascular events. The role of laboratory predictors of renal dysfunction in the progression of cardiovascular disorders is discussed. The general approaches of echocardiographic visualization of the heart cavities and its importance in the diagnosis of cardiovascular diseases are discussed. Special attention is paid to the development of pulmonary arterial hypertension, changes in the left and right ventricle of the myocardium with renal dysfunction