The report of the Russian Kidney Replacement Therapy Registry represents data on the national and regional levels for the period from 2015 to 2019. Detailed information about the treatment of end-stage kidney disease incidence and of prevalence patients on hemodialysis, peritoneal dialysis, and with functioning kidney graft is provided.

Vitamin D is a steroid hormone (D-hormone) long known for its important role in the regulation of mineral metabolism, bone mineralization and the functioning of the parathyroid glands (PTH). It has been established that vitamin D (25(OH)D) deficiency is one of the risk factors for the development of various diseases, such as cardiovascular pathology, diabetes mellitus, obesity, malignant neoplasms in the general population, but its relationship with the morbidity and mortality of patients with chronic kidney disease (CKD) is not well understood. The interest of nephrologists in the active metabolite of vitamin D (VD) and its influence beyond the classical effects have increased over the past few years, due to the fact of the discovery of specific VD receptors (VDR) localized in the nuclei of cells of many organs and tissues that are not associated with mineral metabolism. In recent years, the understanding of the role played by VDRs and the consequences of their activation has changed dramatically. Several studies have analyzed the differences between various VDR activators (agonists) and proposed a new concept for selective VDR activation. The spectrum of D-hormone-mediated effects has been extended to pleiotropic extraskeletal actions. In this review, we cover in detail the physiology of vitamin D and the effect of numerous endogenous and exogenous factors on it. We separately discussed the metabolic disbalance of vitamin D in different stages of CKD, a close link between it and FGF23 secretion and the level of α-Klotho. In the section on the role of VDR activators in secondary hyperparathyroidism treatment, we looked at the possibilities of the full spectrum of vitamin D metabolites in PTH secretion suppression and influences on calcium and phosphorus serum levels. Here are the results of recent meta-analyses comparing efficiency and safety selective and non-selective VDR activators. Finally, we presented advances in new areas of therapeutic use selective VDR activator paricalcitol as reno- and cardioprotector and also argued for its potential role in the prevention of different chronic non-infectious diseases in patients with CKD.

The most important feature of acute kidney injury (AKI) in COVID-19 is the absence of a single main link of pathogenesis. A thorough understanding of the mechanisms and main links of the pathogenesis of the disease will allow the identification of early markers of AKI, which will contribute to early diagnosis, prognosis, personalized therapy and prevention of kidney damage in patients with COVID-19. Aim: to summarize data from clinical and scientific studies on the known mechanisms of AKI in COVID-19. To identify markers of early kidney injury in COVID-19. Materials and methods. In the Web of Science, Scopus and RSCI databases, 81 sources were selected that contained relevant data from clinical and scientific researches on the topic of this review. Results: the main reported mechanisms of kidney damage in COVID-19 patients are as follows: intracellular activity of the virus leading to cell death, excessive release of pro-inflammatory cytokines and cytokine storm, pathology of the renin-angiotensin-aldosterone system (RAAS), hyperergic inflammation and immunothrombosis. The main effects of angiotensin II in the case of dysregulation of the RAAS, as well as the spectrum of pro-inflammatory cytokines and their functions in the development of the cytokine storm, were determined. The possibility of a direct cytopathic effect of SARS-CoV-2 on the renal epithelium as an independent cause of AKI in COVID-19 was considered. The association between the hyperergic inflammatory response and the process of immunothrombosis, which is mediated by many defense systems, including neutrophils, platelets and proteins of the complement system was presented. The risk of thrombotic complications in the renal vessels in patients with COVID-19 was anaysed. An analysis of potential early biomarkers of kidney injury in COVID-19 were also presented and compared with clinical biomarkers of AKI. Conclusions: AKI is one of the most common complications in critically ill patients with COVID-19, which significantly worsens the prognosis of the disease. The study of the mechanisms of kidney injury contributes to the discovery of new markers necessary for early diagnosis, prognosis of the course of the disease, and further determination of the optimal personalized therapy.

The multifactorial origin of thrombotic and thromboembolic complications in nephrotic syndrome (NS) is reviewed. In total, the primary and secondary NS increase the risk of developing venous and arterial thromboembolic complications by a factor of 8 in comparison with the 10-year general population risk. The most common are venous thrombosis (deep vein thrombosis, renal vein, vena cava inferior, portal vein, mesenteric and intracranial veins), while arterial thromboses with limb or brain damage are much more rare. In general, the development of thrombosis is much more often observed in adult patients with NS, the incidence of thromboembolism in them is 25%, while in children it is about 3%. Risk factors for the development of venous thrombotic complication (VTC) in patients with NS can be divided into traditional (modifiable and unmodifiable) and associated with NS. The modified ones include hospitalization, VTC in the past, prolonged immobilization (>3 days), therapeutic and diagnostic manipulations (central and peripheral venous catheters), acquired thrombophilia (antiphospholipid syndrome, hyperhomocysteinemia), autoimmune glomerulopathy, malign neoplasms, obesity. Unmodified factors include old age and hereditary thrombophilia. NS can be combined with genetic markers of thrombophilia (factor V Leiden (G1691A), factor II (G20210A), plasminogen activator inhibitor-1 (PAI, 4G/ 4G, 4G/5G), folate cycle enzymes - methylenetetrahydrofolate reductase (MTHFR) genes mutations). However, the number of studies is limited and the results are conflicting. This underlies the ongoing discussion about the need to screen these markers in patients with NS. Risk factors for VTC associated with NS include hypohydration, acute kidney injury, use of diuretics and glucocorticosteroids. The preventive therapy of thrombotic and thromboembolic complications of NS is rather difficult, it is based on the assessment of the “benefit-risk” balance: a decrease in the risk of thrombotic events in assessing the risk of hemorrhagic complications.

A kidney biopsy is the "gold standard" for the diagnosis of kidney diseases and a mandatory diagnostic procedure for suspected glomerular pathology. The aim of this study is a retrospective analysis of the renal biopsy register data, performed over 7 years, with an assessment of the pathology structure depending on the indications for biopsy and the age of the patients. Material and methods: a retrospective study based on the results of 6387 biopsies of native kidneys performed from 2013 to 2020 at the Moscow City Nephrology Center. Results: the most common indications for kidney biopsy were isolated urinary syndrome, the nephrotic syndrome and renal failure (33%, 32.5% and 27% of cases). Less biopsy was performed at acute nephritic syndrome (3.5%) and for evaluating the morphological picture already diagnosed systemic disease (4%). The main causes of the nephrotic syndrome were membranous nephropathy (MN) - 27%, focal segmental glomerulosclerosis (FSGS) - 22%, minimal change disease (MCD) - 21%, amyloidosis - 13%, and diabetic nephropathy (DN) - 6%. In children, the majority of cases were presented by MCD (59%) and FSGS (30%), and in persons over 65 years of age, the main causes of the nephrotic syndrome were MN (30%) and amyloidosis (28%). Renal failure was most often caused by nephrosclerosis of various nature (including the outcome of IgA nephropathy), which prevailed in children (48%) and middle-aged patients (39%), as well as crescentic glomerulonephritis, which was the main cause of renal failure in patients over 65 years of age (33%). The rate of thrombotic microangiopathy (TMA) decreased from 14% in children to 8% and 1% in middle-aged and older patients. In middle-aged patients with the isolated urinary syndrome, IgA nephropathy was the main cause (58%), but in children, hereditary nephritis (42%) prevailed, while in patients over 65 years old it was secondary forms of FSGS (23%). In acute nephritic syndrome, cases of IgA nephropathy also prevailed (38%), but in half of cases, various forms of proliferative and membranoproliferative glomerulonephritis were detected. Their nature at the time of biopsy could not always be verified. Among the biopsies performed to precise the morphological pattern of an already diagnosed systemic disease, in most cases, it was systemic lupus erythematosus (76%), followed by Schönlein-Henoch purpura (10%), amyloidosis (2.3%) ANCA-vasculitis (2%), cryoglobulinemic nephritis (3%) and TMA (1.6%). In 4.7% of cases, the morphological examination did not allow us to confirm the initial diagnosis. Conclusion: renal pathology includes a wide spectrum of diseases, which differ significantly depending on the indications for the biopsy and the age of the patient.

Aim: to investigate the risk factors for severe hypocalcemia (SH) after parathyroidectomy (PTx) in dialysis-treated CKD stage 5D patients with secondary hyperparathyroidism. Materials and methods: we performed a retrospective cohort study included 318 severe SHPT dialysis-dependent patients who underwent successful subtotal or total PTx with autotransplantation of parathyroid tissue. Severe postoperative hypocalcemia was defined as an ionized serum calcium level less than 0.9 mmol/l on a day 2 after surgery. Results:The incidence of early postoperative SH in our cohort was 66% (210 from 318). Univariate analysis showed that SH patients in comparison with non-SH group were significantly younger (44 [37; 54] vs 52 [43; 59] years, р<0.0001), had higher baseline PTH (134 [99.6; 185] vs 89 [67.5; 114] pmol/l, р<0.0001) and alkaline phosphatase (AP) levels (380.6 [191; 681] vs 130 [96; 175] IU/l, р<0.0001), lower baseline serum total calcium (Ca) level (2.46±0.22 vs 2.57±0.21 mmol/l, р<0.0001) and ionized Ca (1.2 [1.11; 1.28] vs 1.28 [1.21; 1.36] mmol/l, р<0.0001), higher ΔPTH before/after surgery (126 [90.6; 175] vs 81.1 [60; 105.1], р<0.0001). The multivariate logistic regression revealed AP level as the only independent risk factor of severe hypocalcemia development after PTx (OR 3.8 [1.7; 8.2] per each 100 IU/l, р=0.001). Sex, dialysis vintage, RRT modality (hemodialysis or peritoneal dialysis) and type of surgery were not associated with risk of SH (р=0.55, 0.21, 0.27 and 0.81, respectively). In nested models excluding AP significant factors of postoperative SH were preoperative PTH (OR 1.03 [1.02; 1.032] per each pmol/l, р<0.001), ΔPTH before/after surgery (OR 1.03 [1.02; 1.034] per each pmol/l, р<0.001), age (OR 0.96 [0.94; 0.99] per a year, р=0.003), baseline total serum Ca (OR 0.2 [0.05; 0.78] per each mmol/l, р=0.021). The length of hospital stay was significantly longer in SH patients (р=0.0016). Conclusions: the preoperative AP level was the most important predictor of the development of severe postoperative hypocalcemia in patients after PTx due to secondary hyperparathyroidism. In addition, important risk factors may include young age, low baseline total calcium levels, high PTH levels before surgery.

Aim: to assess the function of the parathyroid glands (PTG) and the prevalence of HPT in patients after KT and to determine the factors predicting the normalization of serum PTH early after surgery. Methods: single-center study included 230 patients. The duration of renal replacement therapy before transplantation was 0 months-23 years, the post-transplant period was 12-96 months. Glomerular filtration rate (eGFR) was calculated using the CKD-EPI formula; stages of chronic kidney disease (CKD) were determined by eGFR. Results: the median eGFR was 51 ml/min (Q1-Q3: 39; 65): 3.5% patients had CKD 1 (KT) stage, 33.9% - CKD 2 (KT) st., 49.1% - CKD 3 (KT) st., and 13.5% patients - CKD 4 (KT) st. The median serum PTH was 120 pg/ml (Q1-Q3: 87; 182): respectively 99 pg/ml (76; 120), 98 pg/ml (79; 123), 120 pg/ml (89; 180) and 267 pg/ml (170; 328) in patients with CKD 1, 2, 3 and 4 (KT) st. (р<0.001). The frequency of HPT was 19.8% in patients with eGFR ≥60 ml/min, 38.1% and 93.5% in patients with CKD 3 and 4 (KT) st. (р<0.001). In the first five years after kidney transplantation, HPT was diagnosed in 30.3% of patients, in subsequent years in 54.7% of them (р<0.001), with a frequency of reduced graft function (eGFR <60 ml/min) - in 55.5% and 77.3% of patients, respectively (р=0.002). A retrospective analysis showed that the predisposing factors for the normalization of the function of the PTG in three months after KT were absence of HPT and hyperphosphatemia before KT (respectively, RR 1.41 95% CI 1.19; 1.66, р<0.0003; RR 1.44 95% CI 1.08; 1.90, р=0.014) and immediate and good graft function after surgery (respectively, RR 1.55 95% СI 1.22; 1.96, р=0.0006; RR 1.36 95% CI 1.06; 1.73, р=0.015). Conclusion: HPT occurs in 34.5% of patients in the early period after KT. The factors predisposing the normalization of PTG function three months after KT are pretransplant target levels of PTH and blood phosphorus, immediate and satisfactory renal transplant function. In the five-year post-transplant period, HPT occurs in 30.3%, in subsequent years in 54.7% of patients that associated with a decrease in the function of the kidney.

The risk of neoplasms development among kidney transplant (KT) recipients is twice higher than in the general population. The frequency of renal cell carcinoma (RCC) occurrence in KT recipients is about 0,6%. RCC more often develops in the native kidney than in KT (0,7% vs 0,2%). Several histopathological features in KT recipients were noted: reduced frequency of clear cell carcinoma (CCC) and wider distribution of papillary cell carcinoma in comparison with the general population. CCC is the most aggressive type of RCC in terms of metastasis and worst prognosis. The majority of KT tumors are asymptomatic and detected by accident. Presently, contrast-enhanced multispiral computed tomography (CEMCT) is considered to be the gold standard of noninvasive diagnostics of RCC. Since the 2000s, contrast-enhanced ultrasonography (CEUS) has been actively implemented. This technique demonstrates results comparable to CEMCT. The article contains a brief overview of CEUS diagnostic capabilities in cases of RCC and highlights some technological and practical aspects of CEUS application in real clinical practice. The clinical case of diagnostics and successful surgical intervention in the patient with RCC and preserved KT function is presented. The perfusion pattern of rapid contrast media wash-in and wash-out during CEUS in a patient with histologically verified CCC was demonstrated. The patient underwent laparoscopic resection of the KT tumor. The diagnosis of CCC was finally verified by the results of histological examination. KT function was not affected during and after the surgery. To the best of our knowledge, this clinical case is the first description of CEUS application in a KT recipient with CCC in the Russian Federation. The presented data allows introduction the capabilities of CEUS as a diagnostic link in nephron-sparing strategy to a wide audience of clinicians.

Atypical hemolytic-uremic syndrome (aHUS) belongs to a group of thrombotic microangiopathies (TMA) characterized by profound injury to almost all organs and systems in the absence of specific treatment. Timely diagnosis and early initiation of complement-inhibiting therapy largely define the prognosis. In the presented case, aHUS was diagnosed in a 29-old female patient three weeks after the debut. The disease manifested in the context of diarrhea and resulted in progressive renal failure eventually requiring renal replacement therapy (RRT). Laboratory findings characteristic of TMA (hemolytic Coombs-negative anemia with schizocytosis, thrombocytopenia and high serum LDH) did not reach the diagnostic criteria thus the renal biopsy was required and performed. Biopsy morphology came consistent with TMA. Additional examination ruled out some secondary forms of TMA and thrombotic-thrombocytopenic purpura. At that point, aHUS diagnosis was beyond doubt. Therapeutic plasma exchange was initiated and sustained for the induction and maintenance of remission before eculizumab administration, while the patient still required dialysis. The patient also received combined antihypertensive therapy and low-molecular-weight heparin. The plasma exchange course was complicated by life-threatening allergic reactions to FFP, requiring administration of high-dose glucocorticoids. Attempts at plasma exchange cessation resulted in aHUS relapse with extrarenal symptoms - convulsions with consistent ischemic lesions in the brain structures. Plasma exchange resumption resulted in remission shortly after initiation, including resolution of ischemic brain lesions. PE dependence resulted in 8-month hospital stay, with 55 plasma exchange therapies performed. The opportunity to begin the targeted therapy presented only 13 months after the disease debut. From the time of eculizumab initiation, no relapses were registered. Renal function recovery was noted as a significant therapy achievement, allowing withdrawing the patient from dialysis, which was required for 2.5 years. RRT was terminated 15 months after eculizumab initiation. The presented case confirms the efficacy of eculizumab therapy even in the event of delayed administration.

For citation: Tolkach A.D., Parshina E.V., Ivanov A.V., Kislyy P.N. Efficacy of «Gam-COVID-Vac» (Sputnik V) in hemodialysis patients: a preliminary report. Nephrologу and Dialуsis. 2021; 23(3):434-436. doi: 10.28996/2618-9801-2021-434-436