Natalia Chebotareva

Neoangiogenesis is a basic factor for most physiological as well as pathological processes i.e. tumor metastases. The most important is vascular endothelium growth factor (VEGF) and its receptors (VEGFR1/2) in angiogenesis processes. Nowadays antiangiogenic agents (which inhibit VEGF like bevacizumab neither VEGFR2 like ramucirumab) are widely used in very different chemotherapeutic regimens in clinical oncology. The signalling pathway VEGF-VEGFR plays a crucial role in supporting of adequate kidney function. Appearance of antiangiogenic drugs led to adverse nephrotoxic effects: arterial hypertension, proteinuria, rarely nephrotic syndrome, and kidney dysfunction. Various hystological variants of nephropathy are described, however, in most cases, signs of thrombotic microangiopathy of the renal vessels are noted. This literature review discusses mechanisms, clinical and morphological aspects of nephropathy associated with antiangiogenic drugs.

The presented clinical observation reflects the difficulties of differential diagnosis of progressive kidney damage in a patient with sarcoidosis who has undergone a new coronavirus infection. The differential circle included interstitial nephritis as an exacerbation of the underlying disease, acute drug-induced kidney injury, acute glomerulonephritis. Nephrobiopsy confirmed the diagnosis of acute sarcoid tubulointerstitial nephritis with acute tubular necrosis. Timely administration of corticosteroids led to the control of the sarcoidosis process, restoration of kidney function.

Modern view on pathogenesis of immunoglobulin (Ig)A-nephropathy and possible relation to intestinal MALT-system activity is presented in the article. Aberrant glycosylation of IgA and increased association of IgA-nephropathy with intestinal diseases or abnormal intestinal permeability are discussed in details. Based on supposed entero-renal pathogenesis of the disease future treatment modalities are considered. Relevant worlds literature is cited.

Cardiovascular calcification (CVC) makes a significant contribution to the manifestation of cardiovascular complications in patients with chronic kidney disease. Early CVC markers are currently being actively studied to optimize cardio-renoprotective strategies. We performed a prospective comparative analysis of the following factors: FGF-23, a-Klotho, sclecrostin, phosphate, parathyroid hormone, the estimated glomerular filtration rate (eGFR), central systolic pressure as an independent determinant of CVC. Materials and methods. The study included 131 patients with chronic kidney disease 25D st. Serum levels of FGF-23, Klotho, and sclerostin were evaluated using the ELISA method. Vascular augmentation (stiffness) indices, central arterial pressure (using the SphygmoCor device), calcification of heart valves and the degree of aortic calcification (aortic radiography) were also investigated. The observation period was 2 years. Results. According to the Spearman correlation analysis, ...

The present review is focused on risk factors of chronic kidney disease in rheumatoid arthritis (RA). According to recent data, the chronic kidney disease (CKD) in RA patients is more often than at patients without RA. It is closely associated with risk of cardiovascular disease and high mortality. Besides of general population risk factors of CKD, the activity of the disease is independent predictors of reduction in glomerular filtration rate less than 60 ml/min/1.73 m2. In the review, histopathological variants and mechanisms of CKD on basis of international experience are also considered. Suppression of inflammation by basic therapy of RA and biological therapy have changed outcomes RA, prevalence, and structure of kidney involvement in recent years.

Glomerulopathies with nephrotic syndrome that are resistant to therapy often progress to end-stage chronic kidney disease (CKD) and require timely and accurate diagnosis. Targeted quantitative urine proteome analysis by mass spectrometry (MS) with multiple-reaction monitoring (MRM) is a promising tool for early CKD diagnostics that could replace the invasive biopsy procedure. However, there are few studies regarding the development of highly multiplexed MRM assays for urine proteome analysis, and the two MRM assays for urine proteomics described so far demonstrate very low consistency. Thus, the further development of targeted urine proteome assays for CKD is actual task. Herein, a BAK270 MRM assay previously validated for blood plasma protein analysis was adapted for urine-targeted proteomics. Because proteinuria associated with renal impairment is usually associated with an increased diversity of plasma proteins being present in urine, the use of this panel was appropriate. Anothe...

The presentation of kidney damage in Coronavirus disease 2019 (COVID-19) varies significantly. According to recent studies, the development of acute kidney injury (AKI) in severe cases of COVID-19 infection significantly worsens the prognosis of these patients. The pathological changes in kidneys might be caused directly by the cytopathic effect mediated by local replication of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) or indirectly because of systemic immune response or hypercoagulation, so-called immunothrombosis. Other causes, such as hypovolemia and hypoxia, may also contribute to AKI. Acute kidney disease often develops in elderly patients with underlying comorbidities or in critically ill patients with severe respiratory failure. It is known that AKI is a risk factor for mortality in COVID-19 patients.

Chronic kidney disease (CKD) is a non-specific type of kidney disease that causes a gradual decline in kidney function (from months to years). CKD is a significant risk factor for death, cardiovascular disease, and end-stage renal disease. CKDs of different origins may have the same clinical and laboratory manifestations but different progression rates, which requires early diagnosis to determine. This review focuses on protein/peptide biomarkers of the leading causes of CKD: diabetic nephropathy, IgA nephropathy, lupus nephritis, focal segmental glomerulosclerosis, and membranous nephropathy. Mass spectrometry (MS) approaches provided the most information about urinary peptide and protein contents in different nephropathies. New analytical approaches allow urinary proteomic–peptide profiles to be used as early non-invasive diagnostic tools for specific morphological forms of kidney disease and may become a safe alternative to renal biopsy. MS studies of the key pathogenetic mechani...

Eroglu FK et al. studied 31 kidney biopsies with minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). It has been shown that biopsy samples from steroidresistant FSGS patients with CD80+ expression had significantly lower number of Tregs compared to CD80 ( ) biopsies. Approximately 40 years ago, Shalhoub et al. suggested a hypothesis about possible participation of T cells in the developing of MCD and FSGS. However, the pathogenesis is still not fully understood. We also have studied FOXP3-positive cells in the renal interstitium (mm) of 65 adult patients with chronic glomerulonephritis (CGN): 18 patients had FSGS, 16 membranous nephropathy (MN), 11 membranoproliferative glomerulonephritis (MPGN), 20 IgA nephropathy (Table 1). We have also shown that the number of Treg cells in the interstitial compartment in the adult patients with nephrotic syndrome (NS) was significantly lower 2.0 [0.4–4.0] cells/1.5 mm than that in the CGN patients without NS 8.5 [3.0–16.0] cells/ 1.5 mm, P < 0.05. Moreover, we revealed a decrease in the number of Treg FoxP3-positive cells in the tubulointerstitial compartment in FSGS and MN compared with that in other histological variants of CGN (Fig. 1). Treg can suppress the activation of effector and cytotoxic T-lymphocytes either directly or indirectly by activating the production of anti-inflammatory IL-10. Moreover, Treg cells can influence immune cells in the infiltrate (macrophages, dendritic cells, B lymphocytes, and neutrophils) contributing to a switch from the proinflammatory phenotype to the anti-inflammatory phenotype. Eroglu et al. showed the disbalance in the number of Treg cells and CD-80 expression in kidney tissue of children with steroid-resistant FSGS. The possible role of integrins not only for podocytes but also for Tregs in nephrotic syndrome is discussed. Thus, a significant decrease in the number of Treg cells in the renal tissue revealed in patients with NS. The disturbance in regulatory anti-inflammatory mechanisms was more pronounced in steroid-resistant FSGS forms. This data can be of

Recent evidence suggests that interleukin-17 (IL-17) is involved in the pathogenesis of systemic lupus erythematosus (SLE) and it is a promising marker of disease activity in lupus nephritis (LN).1 IL-17 induces the expression of various pro-inflammatory cytokines and chemokines, which increase the influx of various leukocyte subpopulations and thus, causes severe inflammation. These inflammatory mediators enhance the involvement of various leukocyte subpopulations, which ultimately leads to damage.2,3 Nordin et al published interesting data about IL-17 levels in 120 patients with SLE.4 The authors showed an increase in the levels of IL-17 in the serum and urine of patients and their correlations with British Isles Lupus Assessment Group and SLE Disease Activity Index scores, which is consistent with other studies.5,6 But IL-17 was not a sensitive or specific marker of SLE activity. In addition, there was no correlations of IL-17 levels in urine or serum with the histological classes of LN. We also studied the levels of IL-17 in the urine and serum of patients with chronic glomerulonephritis (CGN). The levels of IL-17 in serum did not significantly differ from the levels in healthy individuals and did not depend on the activity of nephritis. On the contrary, the levels of IL-17A in the urine of patients with CGN were significantly higher at 3.05 (2.98-3.1) pg/mg creatinine (Cr) than that in healthy individuals 2.93 (2.92-2.94) pg/mg Cr The urinary IL-17A levels were not correlated with proteinuria (R2 = 0.21, P = .29) and serum albumin (R2 = 0.24, P = .21). These results indicate a connection between IL-17 levels in urine and inflammation of renal tissue in CGN patients. Also, IL-17 levels in the urine were significantly higher in the CGN patients with advanced interstitial fibrosis and a renal dysfunction with glomerular filtration rate less than 60 mL/min/1.73 m2 (2.97 [2.96-2.99] pg/mg Cr vs. 2.99 [2.98-3.00] pg/mg Cr in normal renal function, P < .05) regardless of histological forms. Currently, the role of IL-17 in fibrotic accumulation has been discussed. Severe fibrosis in murine radiation-induced lung disease was more pronounced with regard to reduction in Th1 cells in the presence of increased number of Th17 cells and higher levels IL-17.7 IL-6 can induce glomerulosclerosis and interstitial fibrosis in the kidney directly or through activation of IL-17.8 Changes in the Th17/Treg ratio may contribute to the development of advanced tissue fibrosis by transforming growth factor-β signaling through the activation of mitogen-activated protein kinases.9 Therefore, future research is needed to compare IL-17 levels in the urine with activity and sclerosis scores in the renal tissue and renal outcomes in LN. Natalia Chebotareva1 Anatoliy Vinogradov2 Alla Gindis1 Wenjing Cao1

Heat shock proteins play an important role in immune inflammation and the formation and restoration of proteins. In recent years, the importance of heat shock protein 90 (Hsp90) in the activation of immune inflammation through nuclear factor kB (NFkB) has been discussed. To assess the activation of the Hsp90-NFkB system by measuring serum and urinary levels in patients with chronic glomerulonephritis (CGN). This study included 32 patients with active forms of CGN and 14 patients with Fabry nephropathy. The control group included 10 healthy individuals. Twenty-one out of 32 CGN patients had nephrotic syndrome (NS). Eleven out of 32 CGN patients had proteinuria levels from 1 to 3 g/day without nephrotic syndrome. A total of 17 patients had renal dysfunction (estimated glomerular filtration rate < 60 ml/min/1.73m 2 ). Fourteen patients with Fabry nephropathy had proteinuria without nephrotic syndrome. Serum and urine HSP-90 and NFkB p65 levels were determined using an enzyme-linked immunosorbent assay. The levels of HSP-90 and NFkB in the serum of patients with CGN were significantly higher than in healthy individuals and patients with Fabry nephropathy. In patients with Fabry nephropathy, the HSP-90 and NFkB levels in the urine and serum did not significantly differ from those in the control subjects. Serum Hsp90 levels were significantly higher in the CGN patients with NS than in patients without NS, as well as in patients with normal renal function compared with patients with an eGFR < 60 ml/min/1.73 m 2 and patients with tubulo-interstitial fibrosis. Higher levels of HSP-90 and NFkB in serum were observed in patients with nephrotic forms of CGN, including focal segmental glomerulosclerosis, minimal change disease and membranous nephropathy. There were no correlations between the clinical signs of CGN and urinary HSP90/NFkB levels. Activation of the HSP-90-NFkB system, which is directly involved in the development of immune inflammation in CGN, was found in patients with an active course of CGN, especially in those with nephrotic syndrome.

We evaluated the heat shock system 70 (HSP70) in patients with chronic glomerulonephritis (CGN). Seventy-six patients with CGN patients were included in our study. Ten patients with mild proteinuria (median 0.48 [0.16-0.78] g/24 h) and ten healthy subjects served as positive and negative controls, respectively. Urinary levels of HSP70, interleukin-10, and serum levels of anti-HSP70 were measured by ELISA. The immunohistochemical peroxidase method was used to study the expression of HSP70 and Foxp3+ in kidney biopsies. Treg cells in the interstitium were determined morphometrically. Median urinary HSP70 levels in patients with nephrotic syndrome (NS) [6.57 (4.49-8.33) pg/mg] and subnephrotic range proteinuria [5.7 (4.12-6.9) pg/mg] were higher (p < 0.05) than in positive [3.7 (2.5-4.82) pg/mg] and negative [3.78 (2.89-4.84) pg/mg] controls. HSP70 expression index in tubular cells positively correlated with urinary HSP70 (Rs = 0.948, р < 0.05) and proteinuria (Rs = 0.362, p <...

Abstract INTRODUCTION AND AIMS: Recent studies have highlighted that podocyte injury and decrease in glomerular podocyte number leads to proteinuria (PU) and glomerulosclerosis. Urinary detection of podocyte injury by measurement of podocyturia ...

Background and Aims The pathogenesis of primary focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) remains unknown to date. Some circulating permeability factors are discussed. This work assessed molecule candidates for permeability in serum samples of patients with nephrotic syndrome (NS). Method Forty-one patients with chronic glomerulonephritis (CGN) were included in our study. Seventeen patients had FSGS, 7 patients had MCD, 5 patients had membranoproliferative glomerulonephritis (MPGN), 6 patients had IgA nephropathy, and 6 patients had membranous nephropathy (MN). The laboratory data were compared with the clinical and histological features of nephritis. Serum levels of uPAR and CLCF-1 were measured by ELISA. Results The serum levels of plasminogen activator urokinase receptor (uPAR) were higher in FSGS patients before treatment than in patients with other morphological forms (MCD, IgA nephropathy, MN and MPGN). The levels of uPAR in serum did not corre...