[Impact of kidney biopsy on the management of patients in the rheumatology department: retrospective study].

BACKGROUND: Kidney involvement is a common manifestation of the systemic autoimmune rheumatic diseases. Kidney biopsy is the gold standard for the diagnosis of kidney diseases, however this method has not yet become the standard-of-care in rheumatology practice. AIM: To assess the diagnostic value of kidney biopsy in the management of patients of the rheumatology department. MATERIALS AND METHODS: In this retrospective observational study we analyzed the medical documentation including kidney morphology findings in the patients of the Department of Rheumatology at Tareev Clinic of Internal Diseases. All patients included in the research had signs of kidney involvement and had undergone needle biopsy of the kidney or re-evaluation of the kidney tissue received previously. RESULTS: From June 2016 to October 2021, 3110 patients were admitted to the rheumatology department. Among them 63 (2%) underwent kidney biopsy and were included in the study. Twenty (32%) were male. Mean age was 42.513.9 years. The most common preliminary diagnoses before kidney biopsy were ANCA-associated vasculitis (n=17), systemic lupus erythematosus (n=12), and AA-amyloidosis associated with inflammatory joint diseases (n=7). In 14 (27%) patients diagnosis was unspecified at the time of biopsy. Among 49 patients with established preliminary diagnosis morphological findings were in line 38 (78%) with the pre-liminary diagnosis. However, in 11 (22%) patients morphological findings resulted in the change of the diagnosis. In all 14 patients with unspecified condition kidney biopsy helped to establish clinical diagnosis. Ultrasound evaluation demonstrated hematoma formation in 18 (31%) patients, and among them two required blood component transfusions. CONCLUSION: Our study demonstrates significant value and safety of kidney biopsy in the patients with autoimmune rheumatic conditions. We suggest that kidney biopsy should be implemented in the management of this category of patients.

[Adenocarcinoma of the lung against the background of usual interstitial pneumonia]. / Adenokartsinoma legkogo na fone obychnoi interstitsial'noi pnevmonii.

Lung adenocarcinoma against the background of idiopathic pulmonary fibrosis according to the world literature ranges from 2.7% to 48%, the incidence increases every year after the diagnosis of idiopathic pulmonary fibrosis. We present a clinical and morphological analysis of an autopsy observation of lung adenocarcinoma that developed against the background of corticosteroid-treated usual interstitial pneumonia in a 78-year-old woman. According to the results of histological and immunohistochemical studies, the diagnosis was formulated as: multicentric non-mucinous invasive adenocarcinoma of the right and left lungs with a lepidic growth pattern with background of usual interstitial pneumonia.

[Morphological characteristics of renal changes in Fabry disease]. / Morfologicheskaya kharakteristika izmenenii pochek pri bolezni Fabri.

Fabry disease is an X-linked progressive lysosomal disease caused by a mutation in the gene that encodes the enzyme alpha-galactosidase A and leads to the intracellular accumulation of globotriazylceramide (GL-3). Kidney damage manifested itself as microproteinuria and microalbuminuria, followed by renal failure, is fatal to a patient. MATERIAL AND METHODS: Fabry disease was diagnosed in 5 out of 600 cases of various kidney diseases, by using the 2014-2018 material. Light-optical, immunohistochemical, and electron microscopy methods were used to examine kidney biopsy specimens in Fabry disease. RESULTS: The glomeruli clearly exhibited intralysosomal inclusions, myelin bodies, and fatty vacuoles in the cytoplasm of podocytes, the small processes of which were predominantly reduced. The mesangial space was expanded; the mesangiocytes were in the proliferation state; there were fatty vacuoles in the cytoplasm; the deposits of immune complexes located intramembranously and paramesangially were also found in all cases. An immunohistochemical study revealed that each case was detected to have fixations of IgG, kappa and lambda immunoglobulin chains on the glomerular basement membrane of focal granular pattern. There was fixation of fibrinogen in 3 cases, that of IgM in 2 cases, and that of IgA and complement component 3 in one case. Thus, it can be supposed that although Fabry disease is a lysosomal disease with deposits in the podocytes and mesangiocytes of myelin bodies and fatty vacuoles; however, immunohistochemical and electron microscopic studies cannot exclude the involvement of immune processes in the development of glomerular injury. CONCLUSION: Fabry disease is a rare lysosomal disease accompanied by globotriazylceramide deposits in the podocytes and mesangiocytes. However, at the same time, the fact that immune mechanisms are involved in the development of this disease cannot be denied.

[Artificial intelligence in the diagnosis of prostate cancer]. / Iskusstvennyi intellekt v diagnostike raka predstatel'noi zhelezy.

OBJECTIVE: To discuss the possibilities and prospects of using artificial intelligence (AI) in the diagnosis of prostate cancer (PC). The laboratory diagnosis of PC is considered and prostate images are analyzed according to transrectal ultrasound and magnetic resonance imaging using AI algorithms. Particular emphasis is placed on prostate histologic evaluation.

[Current possibilities of the differential diagnosis of plaque parapsoriasis and the early stages of mycosis fungoides]. / Sovremennye vozmozhnosti differentsial'noi diagnostiki bliashechnogo parapsoriaza i rannikh stadii gribovidnogo mikoza.

Mycosis fungoides (MF) is the most common primary cutaneous epidermotropic T-cell lymphoma (80%). The accurate diagnosis of MF confirmed only by clinical, histological and immunohistochemical signs amounts to 50-75%. OBJECTIVE: To investigate genetic markers (FOXP3, STAT4, IL-12B) for the early diagnosis of MF, to estimate the informative value of used diagnostic techniques (histology, immunophenotyping), and to determine clonality by the T-cell receptor γ-chain genes. MATERIAL AND METHODS: Fifty patients with MF and plaque parapsoriasis (PP) who had been treated at the V.A. Rakhmanov Clinic of Skin and Venereal Diseases and at the National Medical Research Center for Hematology were followed up. A MF group consisted of 27 patients; a PP group included 23 patients, and a control group comprised 10 healthy individuals. The expression of the FOXP3, STAT4, and IL-12B genes was analyzed by TaqMan real time-PCR. The objectives of the study were affected skin portions from patients with MF or PP and healthy individuals. RESULTS: The investigation revealed a increase in the expression level of STAT4 mRNA transcripts by 9 times in patients with MF compared with those with PP and by 553 times in healthy individuals. There was also a statistically significant predominance of the expression level of STAT4 mRNA transcripts in patients with spotted and plaque stages of MF (180; 318) compared with those with PP and healthy individuals, as well as a sharp decrease in those with erythrodermic MF, which was statistically significant. CONCLUSION: MF cannot be diagnosed without comprehensively assessing the clinical, anamnestic, histological, immunophenotypic, and molecular genetic data. The expression level of STAT4 mRNA transcripts is of great importance for the early diagnosis of MF. Inclusion of the level of STAT4 expression in the list of diagnostic signs increases the accuracy of differential diagnosis of MF and PP from 59.1 to 81.8%, respectively.

[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.

[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.

[Incomplete thrombotic microangiopathy as a variant of hemolytic-uremic syndrome].

The described case illustrates difficulties in diagnosing atypical hemolytic-uremic syndrome (aHUS) in incomplete thrombotic microangiopathy (TMA) in the absence of thrombocytopenia, one of the signs of the classic triad of aHUS, which has resulted in the delayed verification of its diagnosis and in progressive kidney injury. The paper discusses the need to carry out kidney biopsy and to include sHUS in both the presence of a complete set of symptoms of this disease and in the absence of one of them into a range of diagnostic search.

[Minimal-change glomerulonephritis in chronic lymphocytic leukemia: A clinical case].

Chronic lymphocytic leukemia (CLL) in association with glomerulonephritis (GN) and renal failure is a serious problem in terms of therapy. The paper reports a clinical case of a 64-year-old female patient with Binet stage C CLL accompanied by minimal-change GN complicated by nephrotic syndrome and the development of acute renal failure. GN was diagnosed on the basis of electron microscopic studies of renal biopsy specimens. It was treated with rituximab in combination with bendamustine. The former was intravenously injected in a dose of 375 mg/m2 on day 0 of the cycle; the latter was given in a dose of 70 mg/m2 within the first 2 days; the cycle was repeated 28 days after initiation of the previous cycle. Five cycles could result in complete CLL remission (the follow-up duration was 20 months); nephrotic syndrome was completely abolished and kidney function recovered.

Telomerase as a tumor marker in diagnosis of prostatic intraepithelial neoplasia and prostate cancer.

BACKGROUND: Early diagnosis of prostate cancer (CaP) can be addressed by studying prostatic intraepithelial neoplasia (PIN) as precancer (high-grade PIN or HGPIN). This article attempts to analyze the diagnostic role of telomerase as an early marker of carcinogenesis. METHODS: Complex urological patient evaluation and assessment of telomerase activity. RESULTS: Out of 92 patients 44% were diagnosed with CaP, 49% with low-grade PIN (LGPIN) in association with benign prostatic hyperplasia (BPH), and 7% with HGPIN in association with BPH. Active telomerase (AT) in prostate biopsy specimens was detected in 98% of patients with CaP, in 33% of patients with HGPIN, and in 20% of patients with LGPIN. In the event of simultaneous detection of AT and PIN in initial prostate biopsy specimens, further monitoring for 0.5-4.0 years revealed CaP development in 50-56% of cases. Further follow-up of patients with PIN and absent telomerase activity in initial biopsy specimens did not demonstrate the development of CaP. The PSA level was significantly higher in patients with active telomerase in the prostate tissue than in telomerase negative patients. CONCLUSIONS: Telomerase activity in the prostate tissue increases the risk of CaP development in patients with PIN. Detection of telomerase activity in prostate biopsy specimens from patients with PIN enables selection of a group of patients with high risk of CaP development and reduction of the number of prostate biopsies performed in other patients.

[Tubulointerstitial nephritis]. / Tubulo-interstitielle Nephritis.

A concept of the pathogenesis of tubular interstitial nephritis (TIN) is presented, based on histologic, immunohistologic and electromicroscopic investigations on 61 patients with glomerulonephritis, lupus erythematodes and rheumatoid arthritis. The pathogenic model is a hypersensitivity reaction which leads to alterations in the tubular basement membrane (TBM) and results in changes in the TBM and secondary damage to stroma, vessels and tubular cells. The findings change depending on the stage, reflecting the transition from an acute to a chronic process. In acute TIN which is generally a drug allergy, the dominant characteristic of the inflammatory process allows the reaction to be categorized in edematous (72%), cellular (23%) and tubular necrotic (5%) types. The cellular types show 4 subdivisions: plasma cellular, eosinophil-granulocytic, lymphohistiocytic and granulomatous. Chronic TIN is in particular characterized through the destruction of the TBM, dystrophy and atrophy of the tubules as well as their degeneration, lymphohistiocytic infiltrates and sclerotic stroma reactions. A distinction is made between cellular destructive and atrophic-sclerotic types. At view of the etiology and pathogenesis a distinction should be made between an infectious and non-infectious TIN and further by the character of the immunoreaction, into a primary and secondary form. If there glomerular changes are present and there is evidence of an immune phenomenon in the glomeruli and TBM we recommend the use of the term glomerulo-tubulo-interstitial nephritis.

[Incidence of glomerular diseases in kidney biopsy materials using WHO classification]. / Häufigkeit glomerulärer Erkrankungen im Nierenbiopsiegut nach der WHO-Klassifikation.

A total of 1,308 renal biopsies performed during the years 1978 to 1983 in Moscow (M, 852 cases) and Rostock (R, 456 cases) showed that 685 (80.4%) and 346 (75.9%), in the two cities respectively, had glomerular disorders when classified according to WHO nosology (Churg and Sobin 1982). Among the 1,031 glomerulopathies from the two cities there were 121 with minor glomerular abnormalities (M: 49 = 7.1%; R: 72 = 20.8%), 145 with focal segmental glomerulopathies (M: 76 = 11.1%; R: 69 = 20.0%), and 765 with diffuse glomerulopathies (M: 560 = 81.6%; R: 205 = 59.3%). The 765 diffuse glomerulopathies from the two series were distributed according to the WHO classification into 77 membranous (M: 63 = 9.25%; R: 14 = 4.1%), 519 mesangioproliferative (M: 380 = 55.5%; R: 139 = 40.2%), 11 endocapillary proliferative (M: 5, R: 6), 99 mesangiocapillary (M: 65 = 9.5%; R: 34 = 10.4%), 2 dense deposit (in R), 4 extracapillary (M: 1, R: 3) and 53 sclerosing glomerulonephritides (M: 46 = 6.7%; R: 7 = 2.0%). Utilization of the WHO classification of glomerular diseases proved to be a useful compromise, allowing two different schools of nephropathology to agree on classification of renal biopsy material. The group of minimal change abnormalities and the focal segmental lesions should be subclassified further according to the clinical and morphologic findings.

Effect of levamisole on cell sensitivity in rats with experimental Heymann's nephritis.

The development of cell-sensitization to renal antigen in rats with experimental Heymann's glomerulonephritis and the effect of levamisole on cell sensitivity have been studied. Morphologic changes in GN rats appeared after 14 days and were most pronounced on days 21-28, with focal proliferation of glomerular cells, an increase of mesangium, a focal increase of the basal membrane material. After day 49 the changes improved slightly and were still the same on day 147 when a location of IgG to the glomerular basal membrane was detected. In every GN rat, cell-sensitivity to renal antigen was revealed from day 21 of the experiment till its end. Levamisole treatment decreased renal morphologic changes and abolished cell-sensitivity to renal antigen. The possible mechanisms of preventing the development of cell-sensitization in rats treated with levamisole are discussed.