Globally, the number of patients undergoing maintenance dialysis is increasing, yet throughout the world there is significant variability in the practice of initiating dialysis. Factors such as availability of resources, reasons for starting dialysis, timing of dialysis initiation, patient education and preparedness, dialysis modality and access, as well as varied “country-specific” factors significantly affect patient experiences and outcomes. As the burden of end-stage kidney disease (ESKD) has increased globally, there has also been a growing recognition of the importance of patient involvement in determining the goals of care and decisions regarding treatment. In January 2018, KDIGO (Kidney Disease: Improving Global Outcomes) convened a Controversies Conference focused on dialysis initiation, including modality choice, access, and prescription. Here we present a summary of the conference discussions, including identified knowledge gaps, areas of controversy, and priorities for research. A major novel theme represented during the conference was the need to move away from a “one-size-fits-all” approach to dialysis and provide more individualized care that incorporates patient goals and preferences while still maintaining best practices for quality and safety. Identifying and including patient-centered goals that can be validated as quality indicators in the context of diverse health care systems to achieve equity of outcomes will require alignment of goals and incentives between patients, providers, regulators, and payers that will vary across health care jurisdictions.

The kidneys are the only place of the absorpted calcium elimination. About 10 g of elemental calcium passes through a glomerular filter per day, while the daily urinary calcium excretion is only 100-200 mg. 99% of the filtered calcium undergoes reabsorption in various parts of the nephron. Dysregulation of the renal calcium handling leads to adverse renal manifestations such as hypercalciuria, nephrolithiasis, nephrocalcinosis, kidney tubular injury, chronic kidney disease. Hypercalciuria is associated with the dysfunction of various molecular regulatory mechanisms responsible for calcium transport in the nephron. The paracellular calcium transport in the proximal tubules and in the thick ascending limb (TAL) of the Henle’s loop is mediated by claudins, a group of membrane proteins of epithelial cell tight junctions. Claudins form cation-selective channels with high permeability to calcium. Deletions of, or mutations in genes encoding renal claudins can cause genetic diseases characterized by hypercalciuria. The main regulator of the paracellular transport of calcium in the TAL is calcium-sensitive receptors (CaSR) of the basolateral membrane of epithelial cells. Various mutations and polymorphisms of CASR gene are associated with hypercalciuria, nephrolithiasis and nephrocalcinosis. In the distal tubules luminal calcium transfer into the cell occurs via specific selective calcium TRPV5 (transient receptor potential channel, vanilloid subgroup) channels, which play a key role in calcium reabsorption. Parathyroid hormone (PTH) is the principle hormone that has been described to regulate the abudance and activity of TRPV5 channels of the distal tubules’ epithelial cells. Moreover, αKloto protein and fibroblast growth factor 23 (FGF23) are involved in the regulation of renal tubule calcium transport in this site of the nephron. Although over the past years major advances have been made in the understanding of the renal calcium transport physiology and its hormonal regulation, at present therapeutic options aiming to reduce hypercalciuria remain restricted. Further effort is necessary for the development of targeted therapy based on the underlying pathophysiological mechanisms of nephrolithiasis.

Modern guidelines discuss in detail the treatment of patients with chronic heart failure (CHF). However, some aspects of biomarkers' use depending on comorbidity have not been sufficiently studied. The aim of this study was to investigate biomarkers of myocardial and renal dysfunction, including hypoxia-1-induced factor (HIF-1), in chronic heart failure, depending on the presence of chronic kidney disease (CKD). Materials and methods. The study included 80 patients with CHF (48 female, mean age 70.1±9.7 years). CHF was diagnosed according to the recommendations for the diagnosis and treatment of CHF of the Russian Society of Heart Failure Specialists (OSSN) and the Russian Society of Cardiology (RKO) - Clinical Guidelines. Chronic heart failure (CHF), 2016. CKD was diagnosed and classified according to the KDIGO guidelines (2012). HIF-1, N-terminal propeptide of natriuretic hormone type B (NT-proBNP), erythropoietin, cystatin C were tested in blood. Results. CKD was diagnosed in 49 (61.3%) patients. The level of HIF-1 was 0.06 (IQR 0.05; 0.08) ng/ml, NT-proBNP was 229.0 (IQR 136.1; 1205.9) pg/ml, erythropoietin was 6.93 (IQR 2.02; 11.6) mIU/ml. No difference was found in HIF-1 in CHF patients with and without CKD. However, in the group of patients with CHF and CKD, NT-proBNP and erythropoietin were an increased. A direct correlation was observed between the HIF-1 and NT-proBNP (r=0.25, p=0.024). Conclusion. HIF-1 in CHF is not associated with kidney function. Patients with chronic cardioranal syndrome have higher levels of erythropoietin and NT-proBNP. The nature of the relationship between erythropoietin and HIF-1 in chronic cardiorenal syndrome requires further study.

Background: unfavorable changes in nutrition and body composition is highly prevalent in patients with chronic kidney disease (CKD) on hemodialysis. Diabetes mellites type 2 (DM2) coupled with CKD should be considered as an additional factor for nutrition abnormalities in dialysis patients due to more a prominent inflammatory status and insulin resistance. Only limited number of investigations addressed the nutritional status of patients with combined CKD and DM2 pathology, in spite of increasing number of patients with diabetes in the dialysis population. Objectives: the aims of our study were to compare the nutritional status in hemodialysis patients with and without DM2 and to evaluate relationship between nutritional status parameters and inflammatory markers. Methods: 79 dialysis patients (50 to 70 years) were divided in two groups: 40 with DM2 and 39 without it. In the DM2 group. None of the patients hade heavy diabetes complications or decompensation. The examination included anthropometry, measurement of body composition by bioimpedance analysis, biochemical assays (including the main parameters of nutritional status and inflammation). All patients kept a 3-days food diary for assessment of nutrient and energy intake. Results: the groups did not differ by age, gender, comorbidity, dialysis duration and adequacy. BMI and degree of abdominal obesity were significantly higher in the DM2 group, but lean mass (LM), handgrip strength and gait velocity were significantly less. The transthyretin level, a more accurate characterizes of protein-energy waste than albumin was significantly decreased in the DM2 group. The levels of AGE and CRP did not differ between the groups, although were twice higher than normal values. Other inflammatory markers (IL1, IL6) were significantly higher in the DM2 group. Protein and energy intake were under dietary recommendations for patients in the DM2 group. A positive correlation between protein intake and levels of albumin and transthyretin and negative association with IL1, IL6 and AGE in patients with DM2 was identified. A negative correlation between LM and CRP was found in patients without DM2. Conclusion: persistent inflammation and sarcopenia were more prominent in hemodialysis patients with DM2. An absence of appetite due to inflammation is a probable cause of low protein and energy intake in those patients.

Obstetric atypical hemolytic-uremic syndrome (aHUS) is considered as a classic complement-mediated TMA, the trigger of which is pregnancy itself. However, there is reason to believe that in women who do not have a genetic defect in the complement system, the induction of acute thrombotic microangiopathy (TMA) requires the presence of additional complement-activating states (CAS) that may complicate pregnancy. The aim of our study was to assess the effect of pregnancy complications on the development, course, and prognosis of obstetric ASH in a large group of patients Methods: 69 patients aged 16 to 44 years with aHUS diagnosed were observed from 2011 to 2019, which developed during pregnancy or immediately after childbirth. Results: in all cases, additional CAS preceded the development of aHUS. The amount of CAS did not significantly differ between patients with pathogenic mutations of complement genes and without them and did not affect the severity of the course of aHUS. The most common combination of CAS was preeclampsia - cesarean section - bleeding. 40 out of 69 patients (58%) received treatment with the complement-blocking drug Eculizumab. Almost a half of them (19 out of 40, 47.5%) received only 1 to 5 infusions. Among 40 patients treated with Eculizumab, complete recovery of renal function was observed in 26 (65%) women, four (10%) retained signs of CKD 4-5 stages, five (12.5%) reached terminal renal failure and 5 patients (12.5%) died. Among 29 women who received only plasma therapy, renal function restoration was noted only in10 (34.5%). An analysis of the development conditions and features of the aHUS course indicates a heterogeneity of the obstetric aHUS. The latter can develop both in genetically predisposed women and in patients without a genetic defect in the complement system. In the latter case, complement activity apparently arises as a result of the interaction of several CAS. This explains the effectiveness of the short-term course of Eculizumab.

Relevance. Chronic kidney disease (CKD) is a global public health problem worldwide associated with an increased risk of cardiovascular and overall mortality. The goal: to identify regional characteristics of the causes and the rate of progression of CKD in a northern territory. The methods: analysis of the data from the patient register of the Department of Nephrology, Komi Republican Clinical Hospital for years 2015-2018, 484 patients 231 men (47.7%), 253 women (52.3%). The average age was 58.8±15.8 years. Result: the average GFR was 30.1±19.3 ml/min/1.73 m2. Distribution by stages of CKD: first stage of CKD - 1.2%, CKD second stage - 5.6%, 3a stage - 13.6%, 3b stage - 12.4%, 4th stage - 26.4%, 5th stage CKD - 26.6%. The main causes of CKD were: tubulointerstitial nephritis (21.5%), diabetic nephropathy (16.7%), chronic glomerulonephritis (15.7%), hypertensive nephropathy (12.0%), uncertain diagnosis (12.8%). The average decrease in GFR was 3.99±2.7 ml/min/1.73 m2 per year of observation. In patients with stage 2 CKD, GFR increased by 8.4 ml/min/1.73 m2 per year, with stage 3 CKD - by 0.13 ml/min/1.73 m2 per year, stage 4 CKD - by 5.17, CKD stage 5 - by 6.8 ml/min/1.73 m2 per year (p=0.034). A direct correlation was found between the rate of GFR declining and the level of phosphates, urea, potassium, proteinuria, erythrocytes sedimentation rate (ESR). An inverse relationship of the rate of GFR declining was found with the level of hemoglobin, GFR, age, and duration of patient’s observation period. The most commonly prescribed drugs for treating patients were ACE inhibitors (32.4%), calcium antagonists (47.5%), HMG-CoA reductase inhibitors (36.4%), beta-blockers (35.1%), diuretics (24.6%), NSAIDs (39.9%). Conclusion: maintaining a regional CKD registry allows one to identify regional features of the structure of CKD causes, assessing the rate of CKD progression and progression factors.

Hypertension and chronic kidney disease (CKD) are highly prevalent conditions worldwide. Hypertension occurs in the adult population in approximately 30% and CKD - in 10-15%. Hypertension occurs in 80-90% of patients with CKD. The lack of effective control of blood pressure (BP) leads to further progression of CKD. Hypertension and CKD were shown to be independent factors of development and progression of cardiovascular disease (CVD). CVD is the main cause of lethal outcomes in patients suffering from CKD. Effective BP control slows down the rate of renal injury and reduces the risk of CVD development. The achievement of target BP values is the main therapeutic strategy for both reno- and cardioprotection. Current understanding of mechanisms of Hypertension formation in CKD and therapeutic approaches to its adequate control are the points for further discussion. Sympathetic overactivity, hyperactivation of the renin-angiotenzin-aldosterone system, salt and fluid retention and the influence of uremic milieu (endothelial dysfunction, oxidative stress, and arterial stiffness) are highlighted as main components of Hypertension pathogenesis. Methodological approaches to clinical diagnosis of Hypertension include BP phenotype, chronobiological patterns and the choice of optimal method of BP measurement. The treatment strategies for effective BP control are presented according to current recommendations and conciliation documents. A wide range of issues related to lifestyle modification, diet restrictions and antihypertensive therapy are discussed in terms of optimal reno- and cardioprotection and cardiovascular risks reduction. Novel forward-looking directions of pharmacotherapy of Hypertension are presented in conclusion.

The article is devoted to actual problem in the diagnosis and treatment of arterial hypertension (AH) in patients on maintenance hemodialysis (MHD). The features of AH pathogenesis and progression inherent in the dialysis population: persistent volume overload, sodium retention, fluctuations in the volemic status, and progressive arterial stiffness were analyzed. One should take into account the clinical significance of other, often underestimated, causes of hypertension in patients on MHD. Among them, the obstructive sleep apnea syndrome, which should be considered as resulting from a volume overload rather than morbid obesity. Side effects of erythropoiesis-stimulating drugs, permanent sympathetic overactivity and persistent hyperactivity of the renin-angiotensin-aldosterone system are also of clinical importance. The contemporary approaches to the treatment of AH are based on results of numerous randomized clinical trials (RCTs) and a number of consensus documents and recommendations. Nonpharmacological methods are based on the improvement of dialysis and dietary strategies aimed on volemia control, preventing sodium retention, achieving and maintaining optimal dry weight. Change in the standard regimen of MHD increasing the number of dialysis sessions per week and its duration, and correction of the dialysate sodium depending on patient's plasma sodium seem also promising. Among dietary strategies, attention should be paid to patients' commitment to lifestyle modification, taking into account their psychological and socio-economic preferences. The pharmacological treatment of hypertension involves the use of modern classes of antihypertensive drugs, considering their pharmacokinetics on MHD, specific side effects and the risk of adverse cardiovascular events. The diagnostic modalities necessary for adequate control of AH are discussed: echocardiography - monitoring for realistic assessment of left ventricular hypertrophy, bio-impedance techniques for stepwise monitoring of dry weight and ultrasound of the lungs to objectify volume overload. Among the promising areas, the large-scale RCTs to determine the target parameters of hypertension and to objectify the effectiveness of existing treatment methods are needed. As an extension of therapeutic and surgical possibilities, it is proposed to pay attention to antihypertensive drugs of central action, renal denervation, renal artery embolization and bilateral nephrectomy.