C3 glomerulopathy is an ultra-rare disease, driven by alternative complement pathway dysregulation, which results in C3 deposition in glomeruli. History of studying the conditions, currently merged under the umbrella of C3 glomerulopathy (С3 GP), counts more than 60 years of capturing substantial changes in the understanding of both pathology and pathogenesis of these diseases. The main pathogenetic factors are either (more commonly) acquired - antibodies against alternative pathway convertases, or (less commonly) genetic - mutations of genes, encoding alternative pathway regulators. The disease phenotype is triggered by autoimmune conditions, infections, or monoclonal gammopathy. The clinical course of C3 GP varies from mild proteinuria and hematuria to rapidly progressive glomerulonephritis syndrome. The decrease of serum C3 levels serving as an important biomarker of the alternative pathway activation is not always detectable; however, normal C3 levels do not rule out C3 GP diagnosis. The key diagnostics tool is immunostaining, demonstrating isolated or dominant C3 expression, while light microscopy commonly, but not exclusively, shows a membranoproliferative pattern of injury. Clinical course and response to the immunosuppressive treatment depend on such factors as genetic predisposition, age of the disease onset, and presence of specific autoantibodies or monoclonal immunoglobulins. Genetic investigations play an important auxiliary role in the diagnostics of genetic forms of C3 GP, genetic abnormalities are important predictors of the response to immunosuppressive treatmentи and they are key determinates for the evaluation of recipients and potential relative donors for kidney transplantation. Response to the currently recommended treatment of the moderate-to-severe C3 GP with glucocorticosteroids and mycophenolates is not universal, however, emerging new molecules against complement cascade factors, as well as clone-oriented treatment, open perspectives for the targeted individualized therapy, which efficacy remains to be further studied and evaluated.

Prevention and treatment of secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD) is a complex problem. Excessive suppression of the parathyroid glands (PTG) leads to the development of hypoparathyroidism and adynamic bone disease. On the contrary, an underestimation of the severity of SHPT can lead to a further increase in blood parathyroid hormone (PTH), the development of disorders of mineral and bone metabolism, cardiovascular and other pathologies, and the formation of tertiary HPT. The modern approach to the correction of SHPT is aimed at personalized prevention of organ damage and the development of tertiary HPT, increasing medical and social rehabilitation and reducing mortality in patients. The therapeutic strategy for SHPT includes individual and simultaneous effects on the main pathogenic factors: hyperphosphatemia, hypocalcemia, vitamin D (calcidiol) deficiency/insufficiency, and excessive secretion of PTH. Control of hyperphosphatemia is essential for the control of SHPT. Current management options - diet and lifestyle changes, regular dialysis treatment, and use of phosphate binders have their benefits and limitations. Neutral calcium balance is maintained by diet, calcium supplements, vitamin D, and dialysate calcium. Native vitamin D has little efficacy in correcting SHPT in the pre-dialysis stage of CKD and is not recommended for dialysis patients. Vitamin D receptor activators (VDRAs) are widely used for the treatment of SHPT. However, VDRAs have calcemic and phosphatemic effects that limit their use to a subset of patients. VDRAs are prescribed to patients with CKD 4-5 st. with the progression of SHPT. A combination of VDRAs and a calcimimetic is recognized as the optimal strategy for SHPT in dialysis patients. Parathyroidectomy is performed in patients with refractory, drug-resistant SHPT. The indication for parathyroidectomy is not only the serum PTH level, which is not clearly defined but also clinical symptoms and HPT-associated complications. A modern therapeutic strategy should increase the effectiveness of the prevention and treatment of CKD-associated HPT.

Aim: to evaluate the relationship between the health-related quality of life (HRQOL) and the medical and social characteristics of patients with CKD on hemodialysis, taking into account the general and dialysis-specific scales of the KDQOL-SF™ questionnaire. Methods: the study involved 723 patients with CKD on hemodialysis living in Moscow. The assessment of the medical and social characteristics of patients was carried out using a questionnaire consisting of 21 questions. To assess HRQOL, the KDQOL-SF™ questionnaire, version 1.3 (Kidney Disease Quality of Life Short Form, v. 1.3) was used for dialysis patients. The study dates August-November 2021. Statistical data processing was carried out using the SPSS program.25. Results: the mean age of patients was 58.7±14.8 years; the proportion of men was 54.6%; married - 56.1%. The median duration of hemodialysis was 48 (IQR, 19-93) months. The means of the "total physical" and "total psychological" components of health were 39.8±9.1 and 43.7±10.9, respectively. Age had a negative impact, and living conditions, financial situation, and physical activity positively correlated with the values of almost all the main HRQOL scales, except for the scales "cognitive functions" and "quality of social interaction". Women had lower rates of HRQOL. Marital status (married), education, and duration of hemodialysis had a positive effect on HRQOL indicators, and high BMI values had a negative effect. Conclusion: a complex of medical and social factors that have a positive or negative impact on the quality of life of patients with CKD on hemodialysis has been identified. Comparative studies on the assessment of HRQOL and factors affecting it among patients on various types of renal replacement therapy (RRT), as well as the creation of an information system for collecting data on HRQOL for all patients included in the register of patients on RRT, are promising.

Pregnancy is a unique condition, with the onset of which the woman's body undergoes various adaptive changes aimed primarily at ensuring proper perfusion of the placenta, which is necessary for a successful pregnancy. The kidneys and cardiovascular system play a key role in the physiological adaptation to pregnancy. Already in the early stages of gestation, the changed in the hormonal background contributes to systemic vasodilation, an increase in circulating blood volume, followed by an increase in renal plasma flow and glomerular filtration rate (GFR). Vasodilation contributes to the activation of the renin-angiotensin-aldosterone system, which leads to sodium retention in the body and an increase of plasma volume. Hypervolemia and an increase in GFR cause a decrease in serum creatinine concentration, which today can be considered a favorable sign of obstetric and renal outcomes. Thus, the normal serum creatinine level in a healthy pregnant woman is always lower than the initial, pregestational one. Glomerular hyperfiltration is so pronounced that the urinary excretion of certain substances exceeds the maximum reabsorption capacity of the proximal tubules, and this leads to the appearance of protein and sometimes glucose in the urine. Hyperfiltration, along with changes in fluid and electrolyte balance, is an integral part of the physiological changes that characterize a healthy pregnancy. Although they are aimed at improving gestational outcomes, they can also be the subject of diagnostic errors if the physician is not aware of the physiology of pregnant women. An increase in the average age of women entering their first pregnancy increases the risk of developing extragenital diseases by the time of conception, including kidney disease, which can affect the characteristics of the adaptation process, which, in turn, can also become a source of diagnostic errors. Nephrologists and obstetricians-gynecologists need to have a clear understanding of the physiological gestational changes in the urinary system, which will contribute to the timely detection of pathology, determining the prognosis, and developing individual tactics for managing pregnancy. This article briefly describes the main mechanisms of the physiological adaptation of the kidneys to pregnancy, including the concept of the "physiological response of the kidneys to pregnancy".

Background. The number of kidney transplantations is increasing worldwide. Therefore, the number of patients with a failed renal graft (RG), returning to dialysis is increasing too. The most common indication for transplantectomy (TE) in patients with late dysfunction is graft intolerance syndrome (GIS). GIS is a reactivation of rejection processes in a failed RG amidst the significant reduction or cessation of immunosuppressive therapy (IST). The diagnosis of GIS is based on clinical and laboratory criteria, including fever, flu-like condition, local pain, tumescence in the graft area, hematuria, anemia, and increased markers of systemic inflammatory response in the absence of a concomitant infectious process. The question of Doppler ultrasound characteristics of GIS remains open. Materials and Methods. A clinical case series of 7 patients (age 25-51 y) with signs and symptoms of GIS is presented (2019-2022 y). At the time of inclusion in the study, all patients received maintenance hemodialysis from 6 months to 3 years. The functioning time of RG was from 9 months to 10 years. Two patients underwent repeated kidney transplantation. All patients underwent a comprehensive ultrasound examination including a Doppler ultrasound evaluation of RG. The special features of TE and subsequent pathohistological examination were studied. Results. All patients demonstrated typical clinical and laboratory signs of GIS (Hb from 74 to 116 g/L, (Me (IQR) 94 [81; 102]), CRP from 12 to 84 mg/L, (Me (IQR) 43 [18; 72]). Most patients had a history of humoral rejection and skipped IST. According to Grayscale examination in all cases thickening pseudocapsule, graft contour unevenness and blurriness of renal pyramids were detected. The increased size of the renal graft was found in 6 patients. Color Doppler mapping demonstrated active intraparenchymal blood flow with disturbed angioarchitectonics and perirenal collaterals. Power Doppler provided a wide variety of spectrums, including collateral and stenotic at different vascular levels. TE was performed in all cases. 5 patients underwent laparoscopic surgery (3 - subcapsular extraction). Median blood loss was 300 mL (IQR) [150; 400]. 2 cases of opened TE complicated by graft bed hematomas and one case complicated by surgical infection. Histopathological examination of removed grafts revealed the signs of acute and chronic vascular rejection. In addition, there was marked narrowing of the arteries of medium and small caliber and signs of severe parenchymal ischemia. Conclusion. All patients with failed RG should be given comprehensive US examination, including Doppler. GIS with active vascular component has characteristic Doppler signs. The presence of perirenal collaterals, active blood flow in failed RG, and fibrous pseudocapsule create additional challenges for TE and require a personalized approach to the choice of surgical tactics.

The spectrum of monocolonal gammopathy of renal significance (MGRS) merges a group of diseases, driven by the deposition of monoclonal immunoglobulins in the patients, who do not meet criteria for diagnostics of multiple myeloma and other blood malignancies. By definition, the diagnosis of MGPS is based on kidney biopsy findings. One of the rare variants of MGRS, defined in 2004, is proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID), presenting with nephrotic syndrome with microhematuria, arterial hypertension, impairment of kidney function, and characterized by a proliferative or membranoproliferative pattern of damage with mesangial and subendothelial deposits of monoclonal immunoglobulin G kappa (IgGκ), or, much rarer - monoclonal IgAκ or IgMκ. Even rarer described PGNMID with monoclonal deposits of the light chain kappa, and we found just one case of PGNMID with monoclonal deposits of the light chain lambda in the literature. Detection of paraprotein in the serum or urine in PGNMIG is possible only in 20-32% of cases and identification of secreting clones in the bone marrow is successful in less than 10% of cases. In contrast with immunoglobulin amyloidosis, heart, and other organ involvement were not described in association with PGNMID. Hypertrophic cardiomyopathy (HCM) is a genetic cardiomyopathy, caused by mutations in the genes, encoding sarcomere proteins, with the autosome-dominant type of inheritance. Diagnostic criteria for HCN is the left ventricular (LV) wall thickening >15 mm in the absence of other cardiac or systemic disease, which can cause LV hypertrophy. Phenotypic overlap between HCV and LV hypertrophy/pseudohypertrophy of other etiology, including arterial hypertension and amyloidosis is common, definite confirmation of the true HCM is possible only with genetic testing. Hereby we present a case of a previously not reported combination of PGNMID with monoclonal light chain lambda deposits and genetically confirmed HCM and discuss the difficulties of diagnostics and differential diagnostics.

Angiogenesis plays a crucial role in the tissue tropism of malignant tumors, as well as determines metastasis and tumor progression. One of the key factors of vascular growth is signaling proteins of the vascular endothelial growth factor (VEGF) family. To date, clinical oncology has introduced several drugs that block messaging via the VEGF pathway. Blocking these signals leads to the disruption of tumor tropism and thus slows down its growth. One such drug is bevacizumab. However, several side effects of VEGF-pathway blockade were also described, including arterial hypertension, renal dysfunction, and proteinuria. There are reports on the development of thrombotic microangiopathy (TMA) and bleeding disorders during therapy with the anti-VEGF drugs group. The article presents a clinical case of a patient who received adjuvant polychemotherapy for colorectal cancer with bevacizumab. Treatment was complicated by KDIGO stage 3 acute kidney injury with features of thrombotic microangiopathy. On examination in our department, anuria, increased BUN level, signs of microangiopathic hemolytic anemia (increased LDH level, schizocytosis) and a significant increase in D-dimer level were noted. The course of the disease was complicated by recurrent intestinal bleeding. A colonoscopy revealed a new solid lesion of tumor growth in the caecum. Because of the unresectability of the tumor lesion, conservative hemostatic therapy was administered. The patient received renal replacement therapy with hemofiltration, and plasma exchange sessions were performed. In 15 days, diuresis was restored. To determine further management tactics, the patient was referred to oncologists. The difficulties of predicting acute kidney injury and of multidisciplinary management of patients with complications of anti-VEGF therapy are discussed in the article.

Two cases of genetic FSGS associated with mutations in the NPHS2 (podocin) and COL4A3 (collagen type IV alpha3 chain) genes are presented. A patient with a mutation in the NPHS2 gene had an early onset of kidney disease at the age of 3 years with a mild proteinuria of 0.33 g/l and a manifestation of nephrotic syndrome (NS) at the age of 13 years. A patient with a COL4A3 gene mutation developed NS at.age of 23 years. In both cases, there was no family history, the steroid-resistant NS was noted, and a patient with an NPHS2 gene mutation achieved partial remission with calcineurin inhibitor. The discussion provides literature data on the prevalence and currently known gene mutations that underlie genetic FSGS in adults. It has been shown that in cases of monogenic FSGS in adults, mutations of the COL4A3 (collagen type 4) and NPHS2 (podocin) genes are the most frequent, mutations of various podocyte protein genes, including the NPHS1 (nephrin), NPHS2 (podocin) genes, are in second place in frequency. LMX1B (LIM homeobox transcription factor 1 beta), COQ8B (coenzyme Q8), IFN2 (inverted formin 2), and others. Some features of the course of genetic FSGS, the time of manifestation of kidney disease, the end-stage.renal disease, possible extrarenal manifestations, as well as cases of partial remission in the treatment with calcineurin inhibitors are provided. The clinical cases presented demonstrate the main trends established in different studies of genetic FSGS in adults. The main directions of treatment of patients with a genetic form of the disease are discussed, for example, the priority of nephroprotective therapy. Thus, FSGS patients with steroid-resistant NS should be tested for mutations, since the identification of the genetic FSGS will allow avoiding long-term immunosuppressive therapy and choosing the optimal treatment strategy.