[Mckittrick-Wheelock syndrome as a rare manifestation of villous adenoma of the rectum]. / Sindrom Makkittrika­Uiloka kak redkoe proyavlenie vorsinchatoi adenomy pryamoi kishki.

McKittrick-Wheelock syndrome is a rare disease when villous adenoma of the distal colon predisposes to profuse watery diarrhea with subsequent severe electrolyte disturbances and acute renal damage. A differentiated approach to correct diagnosis requires in-depth pathophysiological knowledge of regulation of water-electrolyte metabolism, functional and organic disorders of gastrointestinal tract and clinical manifestations of hypoosmolar dehydration. The peculiarity of the McKittrick-Wheelock syndrome is a 100% probability of death without treatment and complete regression of symptoms under complex correction of homeostasis and total resection of tumor. We demonstrate the main clinical trends of the McKittrick-Wheelock syndrome. This report may be useful for general practitioners, gastroenterologists, oncologists, nephrologists and anesthesiologists.

[Study of urinary markers of different podocytopathies by proteomic analysis].

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is a primary podocytopathy characterized by primary podocyte detection and high proteinuria. The search for biomarkers and factors associated with the progression of this disease is an important task nowdays. AIM: To assess the proteomic profile of urine in patients with FSGS and to isolate urinary biomarkers of podocytopathies. MATERIALS AND METHODS: The study included 41 patients diagnosed with chronic glomerulonephritis, 27 men and 14 women. According to the morphological study, 28 patients were diagnosed with FSGS, 9 with steroid-sensitive nephrotic syndrome and 14 with steroid-resistant nephrotic syndrome. The comparison group included 13 patients with membranous nephropathy. The study of the urinary proteome was carried out by targeted liquid chromatography-mass spectrometry using multiple reaction monitoring with synthetic stable isotope labelled peptide standards. RESULTS: The main differences in the protein profile of urine were found in the subgroups of steroid-sensitive (SS) and steroid-resistant (SR) FSGS. In the FSGS SR group, at the onset of the disease, there was a high concentration of proteins reflecting damage to the glomerular filter (apo-lipoprotein A-IV, orosomucoid, cadherin, hemopexin, vitronectin), as well as proteins associated with tubulo-interstitial inflammation and accumulation of extracellular matrix (retinol- and vitamin D-binding proteins, kininogen-1, lumican and neurophilin-2). Compared with the membranous nephropathy group, FSGS patients had significantly higher urinary concentrations of carnosinase, orosomucoid, cadherin-13, tenascin X, osteopontin, and zinc-alpha-2-glycoprotein. CONCLUSION: Thus, in patients with SR FSGS, the proteomic profile of urine includes more proteins at elevated concentrations, which reflects severe damage to various parts of the nephron compared with patients with SS FSGS and membranous nephropathy.

[Gout: from Hippocrates till the modern time].

Gout (podagra) is one of the most ancient articular diseases. Its accurate mechanisms and causes were delineated only during the last century. Major historical investigatory steps are described in relation to causality and pathogenesis of the disease from Hippocrates ages till the modern time. The newest genetic and epidemiologic aspects of the disease are presented in this article.

[Urinary biomarkers of kidney injury in patients treated with anti-VEGF drugs].

BACKGROUND: Antiangiogenic drugs are widely used in oncological practice and are aimed at inhibiting angiogenesis. Despite the high antitumor efficacy, their use may be limited by nephrotoxicity, and therefore the search for early biomarkers of kidney damage remains relevant, which will preserve a favorable safety profile of therapy. AIM: To determine urinary biomarkers of tubular and podocyte damage in patients receiving treatment with antiangiogenic drugs. MATERIALS AND METHODS: The study included patients (n=50) who received intravenous anti-VEGF drugs (aflibercept, bevacizumab, ramucirumab) in various chemotherapy regimens. Concentrations of tubular damage markers KIM-1 (Kidney Injury Molecule-1) and NGAL (Neutrophil Gelatinase-Associated Lipocalin), hypoxia marker HIF-1 (Hypoxia-Inducible Factor 1-alpha) in urine samples were determined by enzyme-linked immunosorbent assay (ELISA) before treatment, and during 8 weeks of treatment. To assess the risk factors for kidney damage, a logistic regression analysis was performed with the inclusion of the main clinical and laboratory parameters. RESULTS: A decrease in the calculated GFR of CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration Formula) of less than 60 ml/min per 1.73 m2 at week 8 of treatment was noted in 42% of patients. An increase in NGAL, KIM-1, HIF-1 and nephrin in urine during the first two weeks of therapy predicted the development of renal damage by the 8th week of follow-up. When constructing ROC-curves, the high sensitivity and specificity of these urinary indicators as prognostic markers were established. Among the clinical and laboratory indicators, independent unfavorable prognostic factors of nephrotoxicity were an initial decrease in eGFR, a history of hypertension, an increase in the concentration of KIM-1 and HIF-1 in urine during the first two weeks of therapy. CONCLUSION: The predictors of renal damage in the treatment with antiangiogenic drugs were previously an increase in NGAL, KIM-1 and HIF-1 in urine during the first two weeks after the start of therapy.

[Evaluation of hemostasis disorders using the thrombodynamic test in patients with chronic glomerulonephritis with nephrotic syndrome].

BACKGROUND: Nephrotic syndrome (NS) is accompanied by a risk of thrombotic complications due to hypercoagulability. Routine laboratory tests are not sensitive enough to detect these disorders, and therefore the use of integral coagulation tests, including a new thrombodynamic test (TT) in patients with NS, is of high relevance. AIM: Using a TT to determine hemostasis disorders in patients with chronic glomerulonephritis (CGN) with NS. MATERIALS AND METHODS: The study included 49 patients with CGN, mean age 37 years, of which 25 (51%) women and 24 (49%) men. Of all the examined patients, 20 (40.8%) of people had NS, 29 (59.2%) had no NS. The process of clot formation was assessed by TT. RESULTS: According to TT, 30% (6/20) of patients with NS and 13.7% (4/29) of patients without NS have hypercoagulation with changes in parameters that go beyond the reference values. In patients with NS, an increase in clot density (D), clot formation rate (V) and clot size (CS) was found, especially when albumin decreased below 25 g/l. Negative correlations were found between the levels of albumin, creatinine and clot density (D), which reflects the level of hyperfibrinogenemia, the rate of clot formation (V) and the integral index of coagulation (CS). The results indicate mainly the activation of the plasma hemostasis due to the internal coagulation pathway. However, the correlation of Tlag (delay time for the onset of clot formation after contact of blood plasma with the insert-activator) with serum cholesterol levels may also indicate activation of the extrinsic coagulation pathway. CONCLUSION: In CGN patients with NS, activation of the plasma hemostasis is noted, as evidenced by an increase in the rate of formation (V) and size of the clot (CS) after 30 minutes, as well as the density of the formed clot (D).

[Risk factors of kidney injury in patients with COVID-19].

AIM: To determine the incidence and risk factors of acute kidney injury (AKI) in Russian cohort of patients with COVID-19. MATERIALS AND METHODS: We included 315 patients, who were hospitalized with COVID-19 from October 2020 till February 2021. The diagnosis was established on the basis of the positive SARS-CoV-2 swab test and/or typical radiologic findings on CT scans. RESULTS: AKI complicated the clinical course in 92 (29.21%) cases. The independent risk factors of AKI were female sex, underline chronic kidney disease and the highest level of C-reactive protein during hospitalization. In the general group of patients were 41 (13%) lethal cases, in the group with AKI 32 (34.8%). Compared with those without AKI, patients with AKI had 4.065 (95% confidence interval 2.154 to 7.671) times the odds of death. Respiratory support, the highest serum creatinine and glucose levels appeared to be the risk factors of death among patients with AKI in the multivariable Cox regression. CONCLUSION: The clinical course of COVID-19 was complicated by AKI in 29% cases. The independent risk factors of AKI in patients with COVID-19 are underline chronic kidney disease, circulatory disorder and the highest level of C-reactive protein during hospitalization.

[Diagnostic and treatment difficulties in kidney damage in the patient with generalized sarcoidosis during COVID-19. Case report].

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.

[Methotrexate-induced lung damage in a patient with rheumatoid arthritis].

We herein report a case of interstitial lung disease secondary to the use of methotrexate in a patient with rheumatoid arthritis. Differential diagnosis between pneumonitis caused by methotrexate in patients treated with basic methotrexate therapy and interstitial pulmonary disease associated with rheumatoid arthritis is based on the clinical examination and instrumental data. The main condition for favorable clinical outcome in all drug-induced lung disease is drug withdrawal, what was proven in our report.

[The Rehberg-Tareev test in assessing the glomerular filtration rate].

The history of glomerular filtration rate assessment is presented, an important step of which was the glomerular filtration rate evaluation by the endogenous creatinine clearance (known as the RehbergTareev test). The article highlights the diagnostic value of the RehbergTareev test and its place among modern methods for assessing glomerular filtration rate.

[Clinical and laboratory signs and risk factors for nephrotoxicity, associated with antiangiogenic drugs].

BACKGROUND: Anti-angiogenic anticancer drugs that block the vascular endothelial growth factor signaling pathway can cause renal damage. Assessment of the risk of nephrotoxicity allows developing optimal treatment approaches and ensuring the relative safety of therapy. AIM: To assess early clinical and laboratory manifestations and risk factors for nephrotoxicity of antiangiogenic drugs. MATERIALS AND METHODS: The study included 50 patients who received antiangiogenic drugs in different regimens of chemotherapy. Demographic factors, body mass index, blood pressure levels, type of antiangiogenic drug, and concomitant therapy were assessed. Before treatment and over a period of 8 weeks, the levels of hemoglobin, number of platelets and schistocytes, D-dimer levels, serum lactate dehydrogenase (LDH) levels, as well as daily proteinuria and serum creatinine and eGFRCKD-EPI were assessed. Linear regression analysis was performed to assess risk factors for nephrotoxicity and arterial hypertension (AH). RESULTS: The median age of patients was 46 [3457] years, 22 (44%) men and 28 (56%) women. AH developed in 52%, a decrease in eGFR in 42%, along with a decrease in hemoglobin levels and an increase in LDH levels at 2 weeks of therapy. The numbers of schistocytes and platelets significantly decreased by 8 weeks of therapy. Risk factors for impaired renal function during treatment with antiangiogenic drugs were an initial decrease in GFR less than 80 ml/min/1.73 m2, an increase in D-dimer levels, and a decrease in hemoglobin levels by 8 weeks of treatment. The risk factors for AH during therapy were the initial decrease in eGFR less than 80 ml/min/1.73 m2 and no prophylactic anticoagulant therapy. CONCLUSION: Early signs of nephrotoxicity of antiangiogenic anticancer drugs were a decrease in eGFR and AH. The independent risk factors for nephrotoxicity were the initial decrease in eGFR, an increase in D-dimer levels, and a decrease in hemoglobin levels at 8 weeks of treatment, while the prophylactic use of anticoagulant therapy reduced this risk in our study.

[Role of the intestinal MALT in pathogenesis of the IgA-nephropathy].

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.

[Low serum Klotho level as a predictor of calcification of the heart and blood vessels in patients with CKD stages 2-5D].

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 percent of calcification increase and the change in Klotho level are most related. According to ROC analysis, a decrease in serum levels of Klotho by 50 units or more is a significant predictor of an increase in aortic calcification of 50% or more with a sensitivity of 86% and a specificity of 77%. Using logistic regression analysis, it was found that a serum Klotho level 632 pg/L predicts an eGFR below a median level of 48 ml/min/1.73 m2 with a sensitivity of 85.5% and a specificity of 78.5%. Wherein OR 17.477 (CI 95% 8.04637.962; p0.001). CONCLUSION: The factor most associated with CVC is Klotho. Decreased serum level of Klotho is a predictor of aortic calcification. In addition, the initial serum level of Klotho is a predictor of eGFR after 2 years.

[The balance of proinflammatory cytokines and Treg cells in chronic glomerulonephritis].

Chronic glomerulonephritis (CGN) is a disease with a steadily progressing course, which is based on inflammation with the activation of immune cells. The severity of the inflammatory reaction in the kidney tissue is determined by the balance of locally pro-inflammatory factors and protective mechanisms, which include anti-inflammatory cytokines and T-regulatory lymphocytes (Treg). The study of processes that can modulate the severity of inflammation in the kidney is of particular interest for understanding the basic patterns of CGN progression. AIM: To determine the clinical significance of the Th17, Th1, and Treg cytokines in urine to assess the activity and progression of chronic glomerulonephritis with nephrotic syndrome (NS). MATERIALS AND METHODS: The study included 98 patients with CGN 37 women and 61 men. Patients were divided into two groups according to the degree of CGN activity. Group I consisted of 51 patients with NS. In 21 subjects, a decrease in GFR60 ml/min was revealed. Group II included 47 patients with proteinuria from 1 to 3 g/day without NS. GFR60 ml/min/1.73 m2 was observed in 26 patients. A kidney biopsy was performed in 65 patients and the hystological diagnosis was verified: 20 had mesangioproliferative GN, 16 had membranous nephropathy, 18 had focal segmental glomerulosclerosis, and 11 had membranoproliferative GN. The control group consisted of 15 healthy people. The levels of IL-6, IL-10, IL-17, tumor necrosis factor a (TNF-a) in the urine were determined using enzyme-linked immunosorbent assay. The number of FoxP3-positive cells in the inflammatory interstitial infiltrate of the cortical layer was determined in 39 patients (in a biopsy sample in a 1.5 mm2 area). RESULTS: In group of patients with CGN, there was an increase in the levels of Th17, Th1, and Treg cytokines in urine TNF-a and IL-10 compared with healthy individuals. An increase in the levels of IL-6 in the urine of patients with high clinical activity of CGN (with NS and renal dysfunction) was more pronounced than in patients with NS and normal renal function. There was a decrease in the number of Treg cells in the interstitium of the kidney and a decrease in the production of anti-inflammatory IL-10 in CGN patients with NS, compared with patients without NS. The most pronounced changes in the cytokine profile were observed in patients with FSGS with an increase in pro-inflammatory cytokines and a decrease in Treg in the kidney tissue/anti-inflammatory IL-10 in the urine. CONCLUSION: An imbalance of cytokines characterized by an increased levels of pro-inflammatory IL-17, IL-6, TNF-a, and a reduced levels of anti-inflammatory IL-10 and T-regulatory cells in the kidney tissue is noted in patients with NS, especially with FSGS. Imbalance of cytokines reflects the high activity of CGN and the risk of the progression of the disease.

[Successful treatment of a rare variant of mesangioproliferative glomerulonephritis with IgM deposits with Cyclosporin A].

We present a case with a rare variant of glomerulonephritis, IgM nephropathy, which occurs mainly with nephrotic syndrome. The clinical features of this variant of kidney damage are characterized; the pathogenetic and the transformation of this form of nephritis into focal segmental glomerulosclerosis are discussed. The development of severe nephrotic syndrome at the beginning of the disease, the formation of secondary steroid resistance have confirmed this hypothesis and have justified the treatment with cyclosporin A aimed at the recovery of the function of the podocyte with remission of nephritis.

[Nephrotoxicity of anti-angiogenesis drugs].

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.

[Clinicopatological variants and risk factors for chronic kidney disease in rheumatoid arthritis].

Recent studies have shown a high risk of chronic kidney disease and associated cardiovascular complications in patients with rheumatoid arthritis (RA), which determines the prognosis. However, the prevalence of chronic kidney disease (CKD) in RA has not been established in the Russians. AIM: Study was to examine the prevalence, risk factors and histological variants of CKD in RA. MATERIALS AND METHODS: 180 patients with rheumatoid arthritis were observed in the Tareev clinic of nephrology, for the period from 2014 to 2019 years. Age, gender, duration of RA, drug therapy, ESR, CRP, DAS28, renal function, proteinuria, histological variants were analyzed. Of the common population risk factors for CKD arterial hypertension, weight index, serum lipids and glucose levels were also assessed. RESULTS: The prevalence of CKD in RA was 19.7%. Age, presence and stage of arterial hypertension, an increase in body mass index, as well as high rates of disease activity ESR, CRP, DAS28 score and duration of RA were risk factors of CKD in RA. Age, duration of the disease, stage of AH and hypercholesterolemia were risk factors in multifactorial regression analysis. Amyloidosis was the most common histologic pattern (50.0%), followed by chronic glomerulonephritis (30.4%) and tubulo-interstitial nephritis (19.6%). Among chronic glomerulonephritis mesangial glomerulonephritis was the most frequent. Renal amyloidosis was associated with a duration of RA, presence of systemic symptoms and CRP level. An isolated decrease in GFR of less than 60 ml/min was detected in 31 (36.0%) out of 86 patients. Сonclusion. The risk factors for CKD in patients with RA are activity and duration of the disease In addition to common population factors. Amyloidosis was the most common histologic pattern associated with duration of RA and inflammatory proteins levels.

[Chronic kidney disease in rheumatoid arthritis patients: prevalence, risks factors, histopathological variants].

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.

[Clinical and pathologic features of nephropathy with C1q deposits].

AIM: To determine the frequency, clinical and morphological features of a nephropathy with C1q deposits in chronic glomerulonephritis adult patients. MATERIALS AND METHODS: 296 specimens of kidneys of patients with a chronic glomerulonephritis (CGN) from 2014 for 2018 were analyzed. At the first step, specimens with C1q deposits in glomeruli revealed by immunofluorescent method were chosen. Lupus nephritis and primary membranoproliferative glomerulonephritis were exclusion criteria. At the second step, the retrospective analysis of the clinical characteristics was carried out. RESULTS AND DISCUSSION: Deposits of C1q in kidneys at 12 of 296 (4.05%) CGN were revealed, m:f ratio 2:1. Average age of the beginning of a disease was 32.1±14.7 years. At a morphological research in 8 membranous nephropathy (MN), in 2 mesangioproliferative glomerulonephritis (MesPGN), in 2 - nephrosclerosis was revealed. Among 12 patients in 5 the disease debuted a nephrotic syndrome, at the others - a proteinuria from 0.5 to 4.0 g/days with the subsequent formation of a nephrotic syndrome. In 5 of 12 patients the disease was characterized by a favor course with preserved kidney function. At 7 patients at the time of inspection decrease in function of kidneys [glomerular filtration rate (eGFR) 31 (30-34) ml/min] was noted. 5 had slow progressing of a renal failure. 2 of 12 progressed to renal failure (eGFR to 19 and 24 ml/min) within a year. CONCLUSION: Deposits of C1q in kidney were revealed in 4.05% of biopsy specimens in CGN. The most frequent morphological form was the membranous nephropathy. The clinical course was characterized by a nephrotic syndrome, more than at a half of patients - with renal dysfunction.

[Modern approaches to the detection of monoclonal gammopathy of undetermined significance (MGUS) in patients with kidney diseases].

Monoclonal gammopathy (MG) is not only the state preceding of hematological neoplasms, but also associated with non - hematological diseases, in particular kidney damage. AIM: To assess the diagnostic value of "Freelite" methods in addition to electrophoresis (EF) and immunofixation (IF) of serum and urine proteins for detecting MG in patients with kidney diseases. MATERIALS AND METHODS: 87 patients with kidney damage, in which MG was established using the method of electrophoresis of serum proteins (EF), immunofixation (IF) and the method of free light chains determination - FLC "Freelite" were selected. The diagnostic value of three - component serum panel was compared with EF and IF. RESULTS AND DISCUSSION: AL-amyloidosis with kidney involvement was diagnosed in 41% patients, cryoglobulinemic glomerulonephritis (cryo GN) - in 18%, chronic glomerulonephritis (CGN) - in 35%, also there was small number of patients with light chain disease and cast - nephropathy. Determination of MG using EP was possible only in 38 (44%). Adding to the serum electrophoretic methods instead of the "Freelite" method, the urine EF and IF reduced the number of missed patients with monoclonal gammopathy from 24 (27%) to 11 (13%), including in the subgroup of patients with AL-amyloidosis but did not reach the sensitivity of the three - component serum screening panel. In 10 (11.5%) MG was represented only by intact mIg with one type of light chain, either κ or λ. Most often - in 25% of patients, intact monoclonal gammopathy was observed in HCV (+) cryo GN. A combination of intact mIgM, mIgG or mIgA with mFLC, was detected in 37 (42.5%). In almost half (46%) of the patients, only mFLC was detected - an abnormal κ/λ ratio. CONCLUSION: The serum screening panel EF + IF + "Freelite" spreads the low - grade monoclonal gammopathy recognition (MGUS) and should be included in the algorithm of examining patients with kidney disease.

[The clinical and morphological characteristics of C1q glomerulopathy]. / Kliniko-morfologicheskaia kharakteristika C1q-glomerulopatii.

C1q glomerulopathy is a rare variety of chronic glomerulonephritis manifested as C1q deposition revealed by immunofluorescence microscopy. The pathogenesis and etiology of the disease have not been studied. The paper deals with the results of clinical, morphological, immunofluorescence, and electron microscopic examinations in 13 patients with C1q glomerulopathy. Light microscopy more commonly revealed membranous nephropathy, mesangioproliferative glomerulonephritis, and nephrosclerosis. Immunofluorescence microscopy detected a C1q fraction in association with other deposits, more frequently IgM and IgG ones. A correlation was found between the clinical presentation and morphological form of chronic glomerulonephritis.