Aim: to compare changes in the main parameters of the complement system in idiopathic membranoproliferative glomerulonephritis (iMPGN), class IV lupus nephritis (LN IV), C3-glomerulopathy (C3-GP) and atypical hemolytic-uremic syndrome (aHUS). Methods: The study included 8 patients with C3-GP (group 1), 13 patients with iMPGN (group 2), 14 with class IV LN (group 3), and 8 with aHUS in remission (group 4). In all patients, the blood levels of complement system components were examined: C3, C4, C3a, C5a, factor H(CFH) and factor B(CFB), membrane attack complex (MAC), antibodies to C3b(anti-C3b-AT) - a component of alternative complement pathway(AСP) C3 convertase, the level of total hemolytic activity (CH50) and the content of factor D(CFD) in the urine. Results: in all groups, C3 and CH50 levels did not go beyond the reference range, however, in the C3-GP group they were at the lower limit, and the C3 level was significantly lower than in the iMPGN and aHUS groups (p=0.03 and p=0.003). An increased level of CFB was detected in all groups, but in the C3-GP it was significantly lower than in the aHUS (p=0.010). C3a levels were increased in the C3-GP and aHUS groups, and a significant difference was found between the C3-GP and iMPGN groups (p=0.003), C3-GP and class IV LN (p=0.041). MAC levels were increased in all groups, however, maximum values, more than 10 times higher than the reference values, were observed in the C3-GP group and reached statistical significance with groups 2, 3, and 4. In the C3-GP group, a strong inverse relationship was revealed between C3 and MAC (r=-0.826, p=0.011), and in the aHUS group - a direct one (r=0.714, p=0.047). There was a strong negative relationship between CH50 and MAC (r=-0.949, p=0.05) and a very strong correlation between CH50 and C3 (r=1.000, p=0.01) in the C3-GP group. Main conclusions: signs of ACP activation were identified in both types of complement-mediated nephropathy, regardless of the stage of disease. In C3-GP, ACP activation is more pronounced than in aHUS after the acute episode of TMA is relieved. With immune complex MPGN, the changes are less pronounced and indicate an activation of complement along the classical pathway.

Aim: to describe the clinical course and outcomes of the anti-glomerular basement membrane (anti-GBM) disease. Methods: in this case series we included patients with anti-GBM disease from different regions of the country. The diagnosis was established based on the clinical and laboratory features (rapidly progressive glomerulonephritis, diffuse alveolar hemorrhage (DAH), anti-GBM antibodies levels exceeding the reference range of the local lab) and/or morphological evaluation (extracapillary glomerulonephritis (ECGN) type I) according to the Chapel Hill 2012 consensus conference definition. Results: We enrolled six cases of anti-GBM disease, one male (24 y.o.) and five females (from 27 to 67 y.o.), who were diagnosed between 2016 and 2023. Among them, five had kidney involvement requiring kidney replacement therapy at the disease onset. Four patients had lung involvement, among them two required invasive ventilation due to DAH at the onset. Kidney biopsy was performed in two cases and showed ECGN type I with 100% crescents in both. All patients received glucocorticoids at an initial dose of 50-60 mg q.d. (prednisolone equivalent), five received cyclophosphamide (four of them oral), and four received plasma exchanges. It should be noted that the treatment regimen was in complete compliance with current guidelines only in two cases. Severe adverse events occurred in five patients, leukopenia and infections being the most common. All patients survived and achieved complete remission. Among five patients with kidney involvement four developed chronic kidney disease stage 5 and continued receiving kidney replacement therapy. Conclusion: management of anti-GBM disease presents a challenge in the real-world practice. Kidney survival remains unsatisfactory.

Background: the frequent combination (comorbidity) of arterial hypertension (AH) and chronic kidney disease (CKD), each of which is a risk factor for the development of cognitive impairment (CI) and dementia, determines the need to diagnose cognitive deficits in these multimorbid patients. Aims: to assess the impact of concomitant CKD and its stages on cognitive functions (CF) of elderly and senile patients with arterial hypertension. Materials and methods: 330 patients aged 60 years and older with essential АH were included in the study and were divided into 2 groups depending on the presence of CKD: group 1 - without concomitant CKD (n=110, mean age 76 [69.8; 82.3] years, 50 (45.5%) women), group 2 - patients with CKD stages G3a and G3b (n=220, mean age 81 [73; 85] years, 118 (53.6%) women). All the patients underwent the assessment of CF using the Montreal Cognitive Assessment (MoCA), Mini-Mental Status Examination (MMSЕ), Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog), Trial Making Test (TMT), Digit Symbol Substitution Test (DSST), Verbal Association Test (literal (letter) and categorical (animal) associations), Boston Naming Test (BNT), Word-Color Interference Test (Stroop color-word conflict test). Results: compared to patients without CKD, patients with CKD stage G3a and G3b had statistically significantly lower average final scores on the MoCA test (23 [21; 25] versus 24 [22; 26] points, respectively, p=0.005) and on the MMSE (27 [25; 29] versus 28 [25.8; 29] points, respectively, p=0.002), among them, patients who scored the lowest number of points on the MoCA test (10-17 points) (p=0.032) and the MMSE (20-24 points) (р<0.001). Patients with concomitant CKD stage G3a and G3b scored a statistically significantly higher number of points when testing according to ADAS-cog (14 [11;18] versus 11 [9; 15] points in the group without CKD, p<0.001), named fewer literal associations (11 [10]; 13] words versus 12 [11; 13], respectively, p<0.001), and had fewer correctly filled cells when performing the DSST test (20 [17; 23] versus 21.5 [19; 25], respectively, p<0.001). Patients with CKD G3b compared with patients with CKD G3a and without CKD had worse results when tested using the MoCА test, MMSE, and ADAS-cog. Conclusion: the results obtained indicate an unfavorable effect of concomitant CKD stage G3a and G3b on the CF of elderly and senile patients with arterial hypertension and a worsening of CF as the severity of CKD increases.

Background. Ejection fraction (EF) and chronic heart failure (HF) are often considered as criteria for the possibility of arteriovenous fistula (AVF) creation due to an increased risk of death, without sufficient evidence for this. There is, however, rare but compelling evidence that low EF increases the risk of AVF dysfunction. Objective. The objective of this study was to evaluate the association between EF at the time of AVF creation and the incidence of adverse cardiovascular events, all-cause mortality, as well as AVF dysfunction. Methods. This retrospective cohort study included 962 adult patients who had a first-time-created functioning AVF. Only patients with a more than three months and less than five years period after AVF creation were included. The mean follow-up period was 34±13 months. Four groups were identified based on EF and the presence of HF at the time of AVF creation: HF with reduced EF (rEF) <40%, with mid-range (mrEF) of 40-49%, or with preserved EF (pEF) ≥50% + HF, and a "no HF" group with EF≥50% and no HF. Results. In the univariate analysis, a reduced EF was associated with an increased risk of mortality, with the hazard ratios (HRs) of 2.706 [95% CI 1.330; 5.507], p=0.006 for mrEF and 8.250 [95% CI 2.621; 25.97], p<0.001 for rEF, compared to the "no HF" group (here and thereafter). However, after adjusting for age, sex, and Charlson Comorbidity Index (CCI), EF was not significantly associated with the risk of death. Only the CCI score remained a significant factor (HR=1.748 [95% CI 1.482; 2.063], p<0.001). A decreased EF was associated with the incidence of AVF dysfunction both in the univariate analysis and after adjustments. In the univariate analysis, the incidence rate ratios (IRRs) of 6.88 [95% CI 3.88; 12.1], p<0.001 for mrEF, and 19.9 [95%DI 8.64; 41.6], p<0.001 for rEF, were shown. After adjusting for age, sex, and CCI, the IRR for mrEF was 8.96 [95% CI 5.81; 13.7], p<0.001, and for rEF, it was 23.4 [95% CI 13.8; 38.6], p<0.001. Even in the presence of polycystic kidney disease and diabetes mellitus in the most comprehensive model, the association between EF and the incidence of AVF dysfunction remained statistically significant: the IRR was 8.61 [95%DI 5.61; 13.1], p<0.001 for mrEF, and 33.4 [95%DI 19.5; 56.2], p<0.001 for rEF. The findings were confirmed after adjusting for urgent HD initiation and in the competing risks survival analysis. Conclusions. In patients who are initiating treatment with maintenance hemodialysis, a decreased EF is associated to a greater extent with a higher risk of AVF dysfunction than with an increased risk of mortality. The burden of comorbidities, rather than a standalone assessment of EF, is one of the major risk factors determining patient survival.

Congenital Anomalies of Kidney and Urinary Tract (CAKUT) are a frequent cause of chronic kidney disease in children and young adults. Anomalies of the CAKUT spectrum are often associated with monogenic conditions and occur both as isolated malformations and in the structure of hereditary syndromes. CAKUT is characterized by marked genetic heterogeneity, incomplete penetrance, and variability of phenotypic manifestations. Objective: to assess the spectrum of inherited genetic defects in a cohort of Russian CAKUT patients, to trace genotype/phenotype correlations. Materials and methods: patients with CAKUT-related chronic kidney disease (5 isolated and 11 syndromal cases) underwent clinical exome sequencing; when analyzing the results, priority was given to the search for rare variants in genes associated with the development of CAKUT (n=91), as well as cystic renal dysplasia/nephronophthisis (n=72). Results: Probable cause of the disease was identified in 7 of 16 patients (44%): EYA1, PAX2, MAFB, KMT2D, GATA3, and TMEM67 mutations were detected. All pathogenic/likely pathogenic variants were identified in syndromal CAKUT varieties only (branchio-oto-renal and coloboma-renal syndromes, multicentric carpotarsal osteolysis, Kabuki and Barakat syndromes, nephronophthisis type 11). One patient was found to harbor rare missense BNC2, NOTCH2, and KMT2D variants of unknown clinical significance. Except autosomal recessive nephronophthisis 11, all identified inherited diseases had an autosomal dominant type of inheritance, with at least 3/6 (50%) of cases being caused by de novo mutations. Interestingly, nephronophthisis, presenting as renal hypodysplasia, demonstrated the absence of cysts and was clinically recognized as CAKUT syndrome. Conclusion: identification of the genetic (monogenic) nature of the disease opens up opportunities for medical and genetic counseling of families and clarification of prognosis, as well as allows timely detection of the possible extrarenal manifestations.

Сardiovascular disease (CVD) is the main cause of the life expectancy reduction in patients with chronic kidney disease (CKD). Endothelial dysfunction (ED) plays a pivotal role in the pathogenesis of CVD. A significant contribution to the development of ED is made by hyperhomocysteinemia. The aim of the study was to assess the prevalence and severity of hyperhomocysteinemia, folic acid (FA), and vitamin B12 deficiency in children with stage 1-5 CKD, as well as to identify the relationship between these factors. Materials and methods: Serum concentrations of homocysteine, FA, and vitamin B12 were assayed in 112 children with CKD stage 1-5 aged from 3.5 months to 17 years 11 months, followed at the Center for Gravitational Blood Surgery and Hemodialysis of St. Vladimir Children's Clinical Hospital in 2021-2022. Results: hyperhomocysteinemia was detected in 51,8% of children with CKD, suboptimal serum concentrations of FA and vitamin B12 were found in 28,6% and 7,1% of patients, respectively. The median serum levels of homocysteine were significantly lower in the group of children with stage 1 CKD, with no significant difference between the groups of stage 2-5 CKD. There was a positive correlation of serum homocysteine concentration with the stage of CKD (ρ=0.300, p=0.002), and negative correlations of homocysteine and vitamin B12 levels (ρ=-0.485, p<0.0001), homocysteine and FA (ρ=-0.394, p<0.0001). Serum homocysteine concentration was significantly higher in children with FA deficiency (Me, Q1-Q3: 20.0 (14.1-28.9) µmol/l vs 11.0 (8.0-14.0) µmol/l, p<0.0001), and significantly lower in children receiving FC supplement (9.9 (7.0-13.4) µmol/l vs 13.1 (9.8-20.5) µmol/l, p=0.014). Conclusion: The inverse relationship of serum homocysteine concentration with FA and vitamin B12, the lower level of homocysteine in children receiving FA confirms the role of these vitamins in the prevention of hyperhomocysteinemia and emphasizees the importance of adequate provision of them to children with CKD.

Glomerular filtration rate (GFR) is the main indicator of kidney function. The purpose of the work was to systematize data on methods for measuring and calculating GFR in the pediatric population and develop an algorithm for a unified approach and a more accurate determination of GFR. The article discusses measurement methods using exogenous and endogenous markers of glomerular filtration and equations for calculating GFR (eGFR), advantages the and limitations of their use. The endogenous markers of GFR: serum creatinine and cystatin C are described in detail. It is emphasized that modern eGFR formulas use the values of these markers obtained only by standardized methods. To standardize the measurement of creatinine concentration, a reference method is used - isotope dilution mass spectrometry (IDMS) and calibrators with a standard reference material (SRM) for creatinine with the assignment of a NIST certification code (for creatinine NIST SRM 967). The transition of laboratories to measuring creatinine concentrations with standardization according to IDMS served as an impetus for the modernization of existing formulas and the emergence of new equations for calculating GFR. International recommendations for the initial assessment of renal function using blood creatinine and eGFR are described in detail, and in certain circumstances where eGFR based on creatinine is less accurate, it is suggested that additional clarifying tests be included. An important component of the article is a detailed description of the GFR calculation formulas in the historical aspect and the rationale for the predominant use of the CKiD U25 and EKFC equations at present. Separate sections of the work are devoted to the peculiarities of assessing GFR in young children, adolescents, and young adults. Particular issues of determining GFR are highlighted, namely: in children with severe somatic, oncohematological diseases, and chronic infections, as well as in patients in critical condition. The conclusion provides a clear algorithm for choosing a formula for calculating GFR and the sequence of conducting clarifying tests if necessary.

Atypical hemolytic uremic syndrome (aHUS) is an orphan disease caused by dysregulation and hyperactivation of the alternative complement pathway, which has a characteristic morphological picture of microvascular lesions and a triad (sometimes incomplete) of clinical manifestations: thrombocytopenia, microangiopathic hemolytic anemia, and target organ damage. Excessive activation of complement in aHUS is caused by mutations in genes encoding proteins of the complement system or the formation of antibodies to some of them. The use of complement-blocking therapy with eculizumab has significantly improved the outcomes of patients with aHUS, including the results of kidney transplantation (KT) in patients at high/intermediate risk of recurrent thrombotic microangiopathy (TMA) after transplantation who are treated with eculizumab prophylactically. However, some patients with aHUS, in the absence of the full complex of symptoms, reach CKD G5 and are included in the waiting list for KT without establishing a correct diagnosis, which can have serious consequences: the return of aHUS in the renal graft with a rapid loss of its function, the development of life-threatening manifestations of systemic TMA. Salvage therapy with eculizumab is known to be less effective than its prophylactic administration in patients at risk of relapse after KT. In addition, in the case of aHUS recurrence in the graft, time for patient evaluation is usually limited. The article presents clinical observations demonstrating the difficulty of diagnosing “missed» aHUS in patients on the KT waiting list and after transplantation. When included in the KT waiting list, special vigilance regarding aHUS should be exercised in adolescents and young patients with severe hypertension, treatment-resistant anemia, episodes of thrombocytopenia, any extrarenal lesions, patients who have had typical HUS, women with CKD C5 after severe preeclampsia/HELLP syndrome, as well as in patients who lost their first renal transplant due to TMA. Such patients should undergo a comprehensive examination, including re-evaluation of medical history (including family history), immunological examination to exclude other causes of TMA, genetic testing of the complement system, determination of antibodies to factor H, and kidney biopsy in the absence of a significant reduction in kidney size and high risk of bleeding.

Sensenbrenner syndrome, also known as cranio-ectodermal dysplasia, is an ultrarare autosomal recessive ciliopathy caused by pathogenic variants in one of six genes including IFT43, IFT52, IFT122, IFT140, WDR19, and WDR35, all encoding proteins that are part of the intraflagellar transport complex A which is involved in retrograde ciliary transport. Sensenbrenner syndrome is a multiple anomaly syndrome with distinctive craniofacial findings (forehead bossing, dolichocephaly), metaphyseal dysplasia (short limbs, small thorax), ectodermal anomalies (sparse hair, small and missing teeth, short nails), connective tissue abnormalities (loose skin, joint laxity), retinal dystrophy, and chronic kidney and liver disease. In this article, we present a 5-year-old male patient diagnosed with Sensenbrenner syndrome as a typical craniofacial and skeletal anomaly with kidney disease and progressive decline in kidney function. The boy is the second child of healthy non-consanguineous parents. His birth weight was 3390 g (50‰) and the birth length was 51 cm (50‰). Clinical examination performed directly after birth, revealed craniofacial and skeletal abnormalities (dolichocephaly, wide forehead, epicanthic folds, telecanthus, narrow thorax, short limbs, brachydactyly, syndactyly of 2-3 toes of both feet). Postnatal kidney ultrasound (US) showed normal-sized kidneys without parenchymal changes. At the age of 14 months, the boy underwent a surgical correction for scaphocephaly. At the age of 2 years the child presented with failure to thrive, US revealed bilateral solitary parenchymal cysts (<1 cm) in both kidneys. At the first admission at the age of 4 years, the boy had short stature, lumbar scoliosis, metabolic acidosis, proteinuria up to 1.0 g/l with elevated urinary β-2 microglobulin level and microalbuminuria, decreased calcium excretion, increased fractional excretion of potassium, sodium, and magnesium. His eGFR was decreased to 54.7 ml/min/1.73 m2. Kidney US revealed a few cysts (RK 1.3×1.6 cm, LK 0.8×0.6 cm) and single medullary calcifications in both kidneys. Oral sodium hydrocarbonate was given to the patient to correct metabolic acidosis. Treatment with ACE inhibitor (iACE) (enalapril, 0.125 mg/kg/d) was started for antiproteinuric and nephroprotective purposes. NGS identified a variant of uncertain significance с.2907G>T (p.Lys969Asn) in exon 25 of the WDR35 gene in a homozygous state. Both parents were found to be heterozygous carriers of this WDR35 variant. 12-month therapy with sodium bicarbonate led to normalization of the acid-base state, and treatment with iACE led to decreasing proteinuria, microalbuminuria, and stabilization of his kidney function (eGFR 50.1 ml/min/1.73 m2).

The aim of the study: - to analyze the course and treatment of COVID-19 in the recipients of the allogeneic kidney at the COVID hospital in Surgut. Material and methods. We performed a retrospective analysis of primary medical documentation (medical records of inpatient individuals) of the patients >18 years old who underwent kidney transplantation surgery, with a new coronavirus infection, admitted to the COVID hospital of the Budget Institution of the Khanty-Mansiysk Autonomous Okrug-Yugra "Surgut District Clinical Hospital" from 25.11.2020 till 19.07.2021. The total number of patients who met the purpose of the study for the specified period was four persons. The examination and treatment of patients was carried out according to the temporary methodological recommendations of the Ministry of Health of the Russian Federation, version 9 (10/26/2020) "Prevention, diagnosis and treatment of new coronavirus infection Covid-19". Results. All patients presented with the cytokine storm and three of them developed acute kidney injury over the chronic kidney disease. The basic immunosuppressive therapy was changed in all COVID-19 patients with allogeneic kidney transplantation. Namely mycophenolic acid was canceled, and the dose of glucocorticoids was increased. All patients received treatment for a new coronavirus infection: off-label genetically engineered biological therapy aimed at relieving the cytokine storm. Three out of four patients were discharged from the hospital with the restored graft function, and one patient with 100% lung injury and sepsis died. Conclusion. Corticosteroid therapy, which is part of the basic immunosuppressive therapy in transplanted kidney recipients, did not prevent the development of a cytokine storm. Currently, it is advisable to develop and approve clear algorithms for the management and routing of patients with new coronavirus infections and kidney transplantation.