The translation of this Guideline was initiated by the Russian Dialysis Society with kind permission of the Academy of Nutrition and Dietetics Under support of Fresenius Kabi Translated by G. Arutyunyan, N. Mikhailova, A. Usubalieva. Edited by I. Ostrovskaya

Cytokine release syndrome plays a key role in the pathogenesis of COVID-19. Therapeutic plasma exchange (TPE) by removing pathogenic cytokines, can favorably influence the course of severe forms of this disease. However, conclusive studies on this issue are still lacking. Only descriptions of individual clinical cases or small cohort studies have been published. There are no data on the use of TPE in patients with renal failure in the literature. The study aims to evaluate the effect of TPE in the severe forms of COVID-19 in patients with advanced renal failure. Material and Methods: a retrospective, uncontrolled, observational study enrolled 211 patients aged 60,4±13,2. 90.5% of them received renal replacement therapy: 66.8% - hemodialysis, 9.5% - peritoneal dialysis, 14.2% renal transplant recipients with moderate to severe dysfunction, and 9.5% had acute kidney injury on chronic kidney disease that did not require dialysis treatment. Results. All patients were divided into 2 groups: 124 (58.8%) patients (treated from 01.07. to 15.12.2020), who received TPE (TPE group), and 87 (41.2%) patients (observed from 01.04. to 30.06.2020), who did not treat with TPE (control group). The condition of patients in both groups at admission was approximately comparable. The clinical picture of the disease was dominated by severe pneumonia. There were no significant differences in inflammatory markers: both groups had no significant differences in levels of CRP, ferritin, lactate dehydrogenase, or D-dimer. The groups also did not differ significantly in lymphopenia, thrombocytopenia, and azotemia. The mortality rate in the group of patients who did not receive TPE was 73.5%, while in the TPE group it was 45.16% (p<0.001). Among patients on chronic dialysis, the mortality rate in the control subgroup was 74.6%, and in the TPE subgroup - 44.15% (p<0.001). Conclusion: therapeutic plasma exchange is an efficient approach to the treatment of severe forms of COVID-19 in patients with advanced renal failure. Its effect, however, may be limited by the risk of death due to uremia.

The review highlights the relevance and significance of the new coronavirus infection, characterizes the virus, the route of invasion, and organ damage. The attention is focused on the risk factors of viral invasion, and the premorbid background of patients. Special attention is paid to the virus interaction with the ACE-2 receptors and the role of the latter in multiorgan dysfunction. The role of the immune system in the antiviral response is covered. We also considered independent predictors of death in new coronavirus infection. The mechanisms of lung damage in COVID-19 are reviewed with particular attention to the pathophysiological mechanism of the synthesis of pro-inflammatory cytokines and the role of the latter in organ dysfunction. A definition of the "cytokine storm" that is usually understood as an overactive immune response with the release of a large number of interferons, interleukins, chemokines, and other mediators is given. The review highlights the most significant and currently known pathogenetic chains of cytokine production. Among them are proinflammatory cytokines, the most significant are Il-1, Il-6, TNF. High cytokine levels are associated with poor outcomes. Special attention is paid to the feasibility and role of anti-cytokine therapy with drugs tocilizumab and sarilumab. It has been noted that treatment aimed at the pathogenetic mechanisms of the development of the "cytokine storm" by antagonists of the Il-6 receptor can interrupt this life-threatening inflammatory response and, consequently, multiorgan dysfunction. The main pathogenetic pathways and risk factors for the development of acute kidney injury (Acute Kidney Injury - AKI) in SARS-CoV-2 have been analyzed. The use of extracorporeal treatment methods, possibly the main methods of combating the massive release of the pool of medium-molecular compounds during the development of a "cytokine storm" are reviewed. It is noted that along with anti-cytokine therapy, extracorporeal methods can effectively reduce the level of proinflammatory cytokines and prevent multiple organ damage. The main issues of expediency, role and place of application of various extracorporeal methods in complex intensive care for new coronavirus infection (SARS-CoV-2) are highlighted.

Introduction: The COVID-19 pandemic has changed the health care system for patients with CKD5. Dialysis patients are at particularly high risk of COVID-19, severe infection, and poor outcomes. Materials and methods: In 2020, in 86 FME RF clinics, 11 331 patients (54.1% - men) received dialysis treatment, 21.8% had DM, 10 717 patients were treated with HD and HDF methods, 614 patients were on PD, and 2854 employees provided medical care. The data were collected using the EuCliD database and statistically processed online at sites https://molbiol.kirov.ru and https://medstatistic.ru. Results: COVID-19 is more often detected in men, patients 40 to 79 y.o., in patients with DM. The rate of sick patients <50 y.o. (31.2% of all treated) was 22.8% of all infected and in the group>50 y.o. (68.8% of all treated), the rate of patients was 77.2%. There were no significant differences between the incidence of COVID-19 infection in groups ≥50 and <60 y.o., ≥60 and <70 y.o., ≥70 and <80 y.o., ≥80 y.o. COVID-19 positive patients (on HD and PD) who died in 2020 - 324 people, were 2.9% of all treated in 2020 and 31.6% of all infected dialysis patients. In FME RF clinics 18.6% and 18.4% of all patients in the RF were treated by HD and PD respectively, but the proportion of mortality from COVID-19 in FME RF clinics was 10.5% at HD and 11.0% at PD respectively. In dialysis centers, FME RF patients with COVID-19 on HD were 2.2 times less than in the dialysis population of RF as a whole (p<0.001), and on PD - 1.98 times less than in RF (p<0.001). In RF patients with COVID-19 on PD and HD, it was found that the mortality rate was significantly lower in patients on PD vs HD (p<0.001). There was no significant effect on the outcomes in COVID-19 patients depending on the method of treatment in FME RF clinics (p=0.349). Conclusion: Patients on dialysis are at greater risk of COVID-19 and fatal outcomes. The administrative, organizational, and medical work of FME RF led to positive results both in the prevention of infection and in treatment outcomes.

Background: COVID-19 in solid organ transplant recipients is usually characterized by a more severe disease course and is often associated with life-threatening complications. Identification of additional factors that may affect the risk and severity of the new coronavirus infection could have a significant impact on choosing a management strategy for renal graft recipients. Aim: to evaluate the possibility of cross-immunity between skin manifestations of viral etiology and COVID-19. Materials and methods: from May 2020 to February 2021 we examined 180 renal graft recipients with a history of transplantation from 2 months to 26.5 years. All patients were categorized into two groups: group I, those who had confirmed moderate or severe COVID-19 disease, and group II, and those without any history of clinical manifestations of the new coronavirus infection (including those with potentially asymptomatic disease). During the study period which lasted for 71 months on average (range, 2 to 318 months), laboratory workup was performed on all patients (on average, twice): dermatological examination and detection of serum antibodies to herpes simplex virus 1, 2, cytomegalovirus, Epstein-Barr virus, COVID-19. Results: in recipients with HPV-associated skin manifestations, the incidence of COVID-19 was significantly lower than in recipients who did not have them: - 30.4% and 50%, respectively, p=0.011. The incidence of new coronavirus infection did not differ in the groups of patients with cutaneous manifestations caused by herpes simplex viruses type 1 and 2 and without them. Among recipients with Epstein-Barr virus seropositivity, there were significantly fewer cases of COVID-19 compared to seronegative patients - 26.2% and 54.8%, respectively, p=0.0002. Conclusion: HPV-associated dermal manifestations of serum EBV-seropositivity in recipients after kidney transplantation is associated with a lower incidence of moderate and severe COVID-19. Further studies are needed to confirm the possibility of cross-immunity against COVID-19 with other infections.

Aim: myeloma cast nephropathy is one of the most serious complications in the course of multiple myeloma (MM), worsening the life prognosis significantly. Since the development of AKI in MM is associated with the production of free light chains (FLC), a decrease in its concentration using extracorporeal techniques can provide a positive effect in the course of the disease. Recently, more and more studies have demonstrated the significant efficiency of the new expanded HD (HDx) technique in removing substances of average molecular weight, but there are only a few studies of the effect of using this technique in the treatment of patients with MM. The aim of this study was to evaluate the effectiveness of HDx technique in FLC removal in comparison with conventional HD (сHD) and high-flow HDF. Method: The study included patients with myeloma nephropathy AKI and indications for an emergency HD start. Each patient underwent sequential procedures: cHD, HDF and HDx. Before the start of the treatment and every 30 minutes during the procedures, the concentration of FLC (kappa and lambda), b-2-microglobulin (β2M), and serum albumin was determined. Results: the study included 7 patients, with a mean age of 68±8 years. In contrast to cHD, a significant decrease in β2M concentration by the end of the procedure was observed both with HDF (by an average of 49±12%, p<0.001) and with HDx (by an average of 59±6%, p<0.001). There was also a significant decrease in the kappa FLC concentration (HDF - 35±34%, p<0.05; HDx - 32±12%, p<0.001) and lambda FLC (HDF - 40±20%, p<0.01; HDx - 31±21%, p<0.05). With сHD, the FLC concentration did not change. There were no significant differences in β2M and FLC concentration decrease between HDF and HDx. None of the techniques resulted in a decrease in serum albumin levels. Conclusion: the HDx technique in patients with MM contributes to a significant decrease in the level of β2M and FLC and does not lead to albumin loss.

Glucose-6-phosphate dehydrogenase is a key enzyme of the pentose phosphate pathway and the main source of the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH). NADPH is a leading cellular reducing agent that plays a central role in cell survival. In a study conducted on 200 white mongrel male rats, the dynamics of changes in the concentration of reduced glutathione, malondialdehyde, as well as the activity of antioxidant defense enzymes (glucose-6-phosphate dehydrogenase, glutathione peroxidase, glutathione reductase, and catalase) in kidney tissues and erythrocytes of laboratory animals under the conditions of intoxication with an X-ray contrast preparation were determined. It was found that the use of the nonionic radiopaque drug omnipak-350 (yogexol) in an average lethal dose leads to a deficiency of glucose-6-phosphate dehydrogenase activity, a decrease in NADPH level, and damage to kidney tissue and endothelial cells. NADPH deficiency, in turn, can affect glutathione reductase activity since this enzyme uses NADPH to convert oxidized glutathione into reduced. The relative insufficiency of reduced glutathione, which is the main low-molecular-weight free radical scavenger and substrate of the glutathione peroxidase reaction, leads to an imbalance in pro-oxidant processes. In the erythrocytes and kidney tissues of rats, against the background of the introduction of the radiopaque drug, activation of oxidative stress was noted in the form of a decrease in the concentration of reduced glutathione and the activity of antiradical protection enzymes, as well as an increase in the content of lipid peroxidation products. These shifts in the activity of antioxidant defense enzymes (catalase, glutathione peroxidase, and glutathione reductase) in animal kidney tissues against the background of the use of radiopaque preparation should be considered as characteristic signs of depletion of adaptive reserves of the cell. The tendency to increase the content of creatinine and urea in the blood plasma of poisoned animals, indicating a decrease in the functional activity of nephrons, and morphological examination of kidney tissues, which revealed signs of activation of apoptosis in renal tissue, served as confirmation of the adequacy of the selected experimental model on animals to study the mechanisms of development of contrast-induced acute kidney injury. The results obtained allow us to conclude that a decrease in the activity of G-6-FDG can serve as a trigger factor for the activation of free radical processes that play an important role in the development of contrast-induced acute kidney injury.

The Charlson comorbidity index was calculated in patients with the serum creatinine level of higher than 265 μmol/L, renal replacement therapy, and kidney transplantation. Therefore only chronic kidney disease (CKD) stages 4-5 were analyzed in elderly and senile patients. This study aimed to investigate the Charlson comorbidity index when included as a "renal" parameter of CKD with an estimated glomerular filtration rate <60 ml/min/1.73 m2 to predict the risk of death in patients with chronic kidney disease of elderly and senile age. Materials and methods. 472 patients (241 women and 231 men, mean age 69.6±7.3 years) with stable cardiovascular pathology of elderly and senile age were examined. CKD was diagnosed according to the National Recommendations «Chronic Kidney Disease: Basic Principles of Screening, Diagnostics, Prevention, and Treatment Approaches» (Scientific Society of Nephrologists of Russia, 2012). The comorbidity of patients was assessed using the Charlson comorbidity index, including corrected for age. CKD with an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 was additionally included in the parameter «moderate, severe kidney disease» when we calculated the Charlson comorbidity index. The follow-up period was 12 months; the primary endpoint was total mortality. Results. CKD was diagnosed in 302 (63.9%) out of 472 elderly and senile patients. CKD with eGFR less than 60 ml/min/1.73 m2 was observed in 277 (91.7%) of 302 patients with CKD. An increase in the CKD-modified Charlson comorbidity index of more than 6 points was associated with the risk of annual mortality in elderly and senile patients with stable cardiovascular diseases (RR 4.7; 95% CI 1.4-15.2; p=0.01 versus OR 1.6; 95% CI 1.08-3.35; p=0.02 with original comorbidity index). Conclusions. Modified Charlson comorbidity index expands the possibility for assessing comorbidity and makes the prognosis for annual mortality in elderly and senile patients with CKD more accurate.

Aim. The presence of chronic kidney disease (CKD) in patients with chronic heart failure (CHF) negatively affects the prognosis, while the severity of both CHF and CKD is different. This study aimed to investigate the prognostic value of biomarkers of hypoxia, myocardial stress, and inflammation in patients with the chronic cardiorenal syndrome (ССS). Materials and methods. This study includes 80 patients over 60 years old with CHF (48 F, mean age 70.7±8.7). CHF was diagnosed according to the Guidelines for the diagnosis and treatment of CHF (OSSN, RKO, 2016). CKD was diagnosed and classified according to the KDIGO guidelines (2012). Biomarkers of myocardial and kidney dysfunction and hypoxia were evaluated: N-terminal propeptide of type B natriuretic hormone (NT-proBNP), cystatin C, hypoxia-inducible factor-1α (HIF-1α), endogenous erythropoietin (EPO). To analyze the pro-inflammatory status in the blood serum, interleukin (IL)-6, IL-8, and IL-18 were studied. The follow-up period was 12 months, the primary endpoint was total mortality. Results. Biomarkers of hypoxia (EPO, HIF-1α, including those corrected for hemoglobin and hypoxia index), NT-proBNP, cystatin C, and IL-6 were significantly higher in the group of deceased patients with CHF than in survivors. CKD was diagnosed in 49 (61.3%) patients with CHF. Patients with CCS had higher levels of eEPO (including those corrected for hemoglobin), NT-proBNP, cystatin C and IL-6, which was not observed for other studied biomarkers. When performing Cox regression analysis (mathematical model χ2=30.7, р=0.0002) and multivariate decision trees (mathematical model χ2=36.8, р<0.0001) to estimate prognosis in patients with CHF, serum EPO (>16,9 mIU/ml), regardless of age, other clinical factors and biomarkers, had a significant impact on annual mortality. In CKD, erythropoietin production decreases, which is a key factor in the development of anemia, but hypoxia caused by CHF additionally stimulates the production of EPO, probably in this regard, we did not observe a low level of EPO in the examined patients with CCS. Conclusion. EPO had a prognostic advantage in a predictive model with biomarkers of myocardial and renal dysfunction, hypoxia, and inflammation, which indicates a determining role of hypoxia, and not only myocardial stress, in the prognosis of patients with CCS.

A nephrologist diagnoses various clinical and laboratory syndromes and their combinations in practice: dyselectrolytemia; nephritic syndrome, nephrotic syndrome, urinary syndrome, anemia, thrombocytosis, leukocytosis, thrombophilia, paraproteinemia, and others. Persistent and severe hyperkalemia can cause the development of ventricular rhythm disturbances, paresis, paralysis, and death, and for these reasons requires treatment. Pseudohyperkalemia does not require treatment and, therefore, it is necessary to differentiate these two conditions promptly to choose the optimal treatment and avoid non-indicated interventions. A search was carried out in the MEDLINE / PubMed, EMBASE, and Web of Science databases using the keywords: pseudohyperkalemia, and kidney disease to study the causes of pseudohyperkalemia, patient management tactics. Violations in the collection, transportation, storage of blood, preparation for analysis, and hemolysis can be the causes of pseudohyperkalemia. Currently, there are two main methods for assessing hemolysis: visual and instrumental. The visual method for assessing hemolysis is poorly consistent with the actual content of free hemoglobin in serum/plasma. An instrumental method based on a photometric method for measuring the content of free hemoglobin (hemolysis index) in the patient's serum/plasma is more accurate. Thrombocytosis, erythrocytosis, and leukocytosis are the causes of pseudohyperkalemia. With thrombocytosis, more than 500 × 109/l and/or erythrocytosis, pseudohyperkalemia in the blood serum is diagnosed. With leukocytosis more than 15-50 × 109/l, reverse pseudohyperkalemia with an increase in the level of potassium in the plasma is verified. The literature presents clinical cases with alternating true hyperkalemia and pseudohyperkalemia in the same patient. Familial pseudohyperkalemia has been also described. The diagnostic criteria for pseudohyperkalemia were determined. Pseudohyperkalemia is verified with an increase in serum potassium levels with normal plasma potassium levels, with a difference between serum and plasma potassium levels of more than 0.4 mmol/l, in the absence of clinical symptoms (weakness, paresthesia, convulsions, paralysis) and changes in the electrocardiogram ("pointed" T waves, lengthening of the PR interval, decrease in amplitude and expansion of the P wave, expansion of the QRS complex, slowing of atrioventricular conduction, and others).

Patients with urolithiasis and/or urinary infection during pregnancy may have obstruction of the upper urinary tract. In the presence of obstruction and urinary infection, obstructive pyelonephritis occurs, which is a life-threatening complication for both the mother and the fetus. In such cases, drainage of the kidney and upper urinary tract is indicated, as a rule, with a ureteral catheter-stent [1, 2]. Permanent drainage of the upper urinary tract by a stent may be complicated by salt encrustation and the formation of stones on proximal and distal rings. The process of stone formation progresses with increasing the duration of the stent in the urinary tract. This is facilitated by the adhesion of pathogenic microorganisms in the form of biofilms on the surface of the stent, which in turn increases the precipitation of salts and causes long-term persistence of the combined microflora. These factors make it difficult and sometimes impossible procedure for stent removal due to its increased rigidity. Researchers have shown that this process is especially rapid in pregnant women with known gestational features of mineral and bone metabolism and urine composition. Therefore, international and domestic recommendations on urology prescribe replacement/removal of ureteral stents no later than 2 months after their installation during pregnancy [1, 2]. In some cases, stone formation on the stent occurs according to an "accelerated schedule" and aggravates the course of pregnancy due to obstructive and inflammatory complications. In such situations, it is necessary to perform puncture nephrostomy and additional endourological interventions [3]. In our clinical case, female patient S., 25 years old, had a stone in the upper third of the left ureter during the first pregnancy. Fifteen (!) urological endoscopic operations were performed due to the massive deposition of salts on the stents, which made it difficult to remove or replace them (Fig. 1, a-e). Repeated drainage was indicated due to obstructive pyelonephritis, however, all installed drains after 2-3 weeks became urate petrified, which in turn was the cause of ureteral obstruction. Pregnancy in patient S. was complicated by fetal distress with negative diastolic blood flow in the umbilical cord artery, fetal heartbeat disorders: cardiotocography is of questionable type, reduction of fetal heartbeats to 90-100 per minute. At the gestational age 33-34 weeks, an emergency cesarean section was performed. The weight of the newborn girl was 1895 g, length - 44 cm, Apgar score - 7/7 points. The newborn needs treatment at the neonatal intensive care unit and then be transferred to the special unit of nursing for premature newborns. The protocol for monitoring pregnant women with ureteral stents should include regular ultrasound examinations of the urinary system and microbiological examinations of urine to prevent the above-mentioned obstructive complications. It is important to strictly follow the recommendations on the timing of removal or replacement of drains. Informed consent for publication of patient's information and images was obtained from our patient. None of the authors has a conflict of interest. Authors contribution: B.N.V. - collection, writing the text, analisis, E.I.P. - writing and correction of the text, supervision, I.G.N. - correction of the text.

Pregnancy management in patients with CKD treated with hemodialysis remains an important interdisciplinary problem that unites the efforts of obstetrician-gynecologists and nephrologists. Currently, such a pregnancy is no longer a rarity. Despite the high incidence of complications for the woman and the fetus, the outcomes of such pregnancies are favorable in most cases with the use of a special dialysis regimen called intensive, which makes it possible to prolong the pregnancy until the birth of a live and viable child by lengthening the weekly dialysis time. Most often, intensive dialysis is used in patients who become pregnant while already receiving renal replacement therapy. There are significantly fewer publications on its onset in pregnant women with advanced CKD (3b-4 stages). As a rule, in such cases, the indication for RRT is not the maternal progression of renal failure but the prevention of the fetotoxic effect of urea on the fetus. This form of dialysis therapy is called protective hemodialysis. A feature of protective dialysis is a shorter duration of dialysis time compared to intensive HD, which is determined by the residual kidney function in a pregnant woman. Dialysis time is determined strictly individually and depends on the volume of diuresis and the ureaconcentration in the mother's blood. The following clinical observation illustrates the possibility of a favorable pregnancy outcome in a patient with stage 4 CKD, in whom protective dialysis was started due to a urea level of more than 20 mmol/l at 23 weeks. The use of an individualized approach made it possible to prolong the pregnancy up to 34 weeks and give birth to a viable child. After delivery, the patient remained dialysis-dependent, and after 10 months she underwent a kidney transplant.

Abstracts of the Young nephrologist's competition, XVII Conference of Russian Dialysis Society