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1.
Ter Arkh ; 87(12): 85-88, 2015.
Article in Russian | MEDLINE | ID: mdl-26978424

ABSTRACT

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.


Subject(s)
Antineoplastic Agents/pharmacology , Glomerulonephritis/diagnosis , Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis , Nephrotic Syndrome/diagnosis , Antineoplastic Agents/administration & dosage , Bendamustine Hydrochloride/administration & dosage , Bendamustine Hydrochloride/pharmacology , Female , Glomerulonephritis/drug therapy , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Middle Aged , Nephrotic Syndrome/drug therapy , Rituximab/administration & dosage , Rituximab/pharmacology
2.
Arkh Patol ; 76(6): 70-77, 2014.
Article in Russian | MEDLINE | ID: mdl-25842930

ABSTRACT

The advent of up-to-date electron microscopes and molecular biological methods for the examination of renal puncture biopsies could define earlier undetectable and unworthy cellular structures and stromas. There is a diversity of diseases that can be diagnosed exclusively at the ultrastructural level, thus the literature has identified the concept of glomerular diseases with organized deposits. The current classifications based only on the ultrastructual deposits are imperfect as they fail to account for the etiological and pathogenetic features included in these diseases.


Subject(s)
Amyloidosis/pathology , Glomerulonephritis/pathology , Aged , Child , Female , Glomerulonephritis/classification , Humans , Kidney/pathology , Kidney/ultrastructure , Male , Middle Aged
3.
Arkh Patol ; 73(3): 54-8, 2011.
Article in Russian | MEDLINE | ID: mdl-21853926

ABSTRACT

Fibrillary glomerulonephritis (FGN) and immunotactoid nephropathy (ITN) are diseases diagnosed only by electron microscopy. Until recently, information on the diseases has reached as reports on some cases. Much information, including the authors' observations, has been presently gathered so as there is a chance of attempting to pool and analyze it. It is quite obvious that investigators do not agree to evaluate FGN and ITN. Some authors are inclined to believe that these are one disease and propose to use the general term "fibrillary-immunotactoid nephropathy", we, like others, consider FGN and ITN as two different diseases. Our findings suggest that there are two diseases (FGN and ITN). We provide support for the data available in the literature on that the deposits are polyclonal in FGN and monoclonal in ITN. It is most likely that no sharp distinction can be made between FGN and ITN from the diameter of microtubules making up deposits (less or more than 30 nm); the procedure of their package and, to be sure, their chemical composition are of importance in establishing the diagnosis.


Subject(s)
Glomerulonephritis/classification , Glomerulonephritis/pathology , Microtubules/ultrastructure , Adolescent , Adult , Child , Female , Glomerulonephritis/diagnosis , Humans , Male , Middle Aged
4.
Arkh Patol ; 73(1): 49-51, 2011.
Article in Russian | MEDLINE | ID: mdl-21506343

ABSTRACT

Immunofluorescence assay has been widely used so far to diagnose glomerular and some skin diseases. The optimal antigen persistence is achieved using the frozen sections; however, their considerable shortcoming is the impossibility to long store preparations and to use a morphology archive. Our laboratory has modified a direct immunofluorescence study on paraffin-embedded renal and skin tissue sections, substantially increasing its accessibility.


Subject(s)
Fluorescent Antibody Technique, Direct/methods , Kidney/metabolism , Kidney/pathology , Skin/metabolism , Skin/pathology , Humans
5.
Arkh Patol ; 70(5): 31-4, 2008.
Article in Russian | MEDLINE | ID: mdl-19137781

ABSTRACT

Fibrillary glomerulonephritis is a rare disease of unknown etiology and pathogenesis. In two thirds of cases, it is clinically manifested by the nephrotic syndrome resistant to cytostatic and corticosteroid therapy. Fibrillary glomerulonephritis is diagnosed by electronic microscopy and characterized by the presence of chaotically located fibrils with an average diameter of 18-22 nm in the deposits of immune complexes. Light optical and immunohistochemical studies are of no crucial importance in this disease. Further investigations may answer a number of questions as to the formation of immune complex deposits and ways of their elimination.


Subject(s)
Glomerulonephritis, Membranous/immunology , Glomerulonephritis, Membranous/pathology , Kidney Glomerulus/immunology , Kidney Glomerulus/ultrastructure , Adolescent , Antigen-Antibody Complex/analysis , Antigen-Antibody Complex/immunology , Cell Proliferation , Female , Glomerular Mesangium/immunology , Glomerular Mesangium/ultrastructure , Glomerulonephritis, Membranous/diagnosis , Humans , Immunohistochemistry , Male , Nephrotic Syndrome/diagnosis , Nephrotic Syndrome/immunology , Nephrotic Syndrome/pathology , Young Adult
6.
Ter Arkh ; 79(6): 10-5, 2007.
Article in Russian | MEDLINE | ID: mdl-17684960

ABSTRACT

AIM: To evaluate contribution of endothelial dysfunction and impairment of endothelial proliferation/ regeneration to mechanisms of development of tubulointerstitial fibrosis (TIF) in chronic glomerulonephritis (CGN) basing on urinary levels of markers of endothelial activation/impairment and angiogenesis factors. MATERIAL AND METHODS: A total of 67 CGN patients entered the study: 19 patients with moderate urinary syndrome (group 1), 37 patients with nephrotic syndrome (group 2), 11 patients with nephrotic syndrome and persistent renal failure (RF). A control group consisted of 12 healthy subjects. The examination covered excretion with urine of Willebrand factor (WF), plasminogen activator inhibitor I (PAL-I), fibrin degradation products (FDP), vascular endothelial growth factor (VEGF). These values were compared with severity of fibrous changes in renal interstitium estimated by biopsy morphometry. RESULTS: CGN patients had signs of affection of parietal effects of vascular endothelium. In particular, increased excretion of functionally active WF, PAI-I and FDP correlating with activity/severity of CGN. The changes were especially noticeable in patients with progressive forms of CGN (with NS and RF). Patients with morphologically verified TIF (interstitial area more than 20%) excretion of endothelial dysfunction markers was higher than in CGN patients free of TIF In a progressive course of nephritis endothelial dysfunction deteriorates by endothelial proliferation/regeneration impairment as shown by reduced urinary excretion of angiogenic factor VEGF and parallel elevation of functionally active WF in urine of patients with severe forms of CGN. Combined contribution of endothelial dysfunction and angiogenesis impairment to mechanisms of TIF development is seen from these values relations with severity of creatinemia and fibrous alterations in tubulointerstitial tissues of the kidney. CONCLUSION: The results point to participation of endothelium in mechanisms promoting development of TIF and RF in CGN both in terms of endothelial dysfunction and impairment of endothelial repair capacity. Clinicomorphological comparisons confirm the significance of WF, PAI-I and VEGF in assessment of local-renal endothelial changes and severity of fibrosis in renal tissue in CGN. Due to availability of the study material, perspectives of fibrogenesis monitoring in the kidneys with the tests appear which is essential for making prognosis and treatment policy in CGN patients.


Subject(s)
Endothelium, Vascular/physiopathology , Fibrin Fibrinogen Degradation Products/urine , Glomerulonephritis/urine , Kidney Tubules/pathology , Plasminogen Activator Inhibitor 1/urine , Vascular Endothelial Growth Factor A/urine , von Willebrand Factor/urine , Adolescent , Adult , Aged , Biomarkers/urine , Biopsy , Cell Proliferation , Chronic Disease , Disease Progression , Endothelium, Vascular/pathology , Enzyme-Linked Immunosorbent Assay , Female , Fibrosis/etiology , Fibrosis/pathology , Fibrosis/urine , Glomerulonephritis/complications , Glomerulonephritis/pathology , Humans , Male , Middle Aged , Neovascularization, Pathologic/complications , Neovascularization, Pathologic/pathology , Neovascularization, Pathologic/urine , Prognosis
7.
Ter Arkh ; 78(5): 9-14, 2006.
Article in Russian | MEDLINE | ID: mdl-16889042

ABSTRACT

AIM: To measure urine and renal tissue levels of profibrogenic mediators (monocytic chemotaxic protein-1-MCP-1 and transforming growth factor beta1 - TGF-b1) in patients with chronic glomerulonephritis (CGN); to specify significance of these mediators for assessment of inflammation and fibrosis in the kidney and as prognosis criteria. ELISA, immunohistochemical tests, morphometry were used to study urine excretion of MCP-1 and TGF-b1, expression of TGF-b1 in renal tissue, interstitial area, respectively, in 63 patients with active proteinuric CGN. RESULTS: Patients with active proteinuric forms of CGN have higher urine excretion of MCP-1 and TGF-b1 than healthy controls. Urine excretion of MCP-1 in patients with nephrotic syndrome was significantly higher than in patients with moderate urinary syndrome. The highest MCP-1 urine excretion was observed in patients with persistent renal failure. Urine excretion of TGF-b1 depended on the level of creatinemia being the highest in marked proteinuria and stable renal dysfunction. Intensive urine excretion of TGF-b1 occurred in CGN patients with expression of this cytokine in renal interstitium. This confirms its local-renal origin. A correlation was found between urine values of MCP-1, TGF-b1 and severity of tubulo-interstitial fibrosis (TIF). High informative value (sensitivity and specificity) of urine MCP-1 and TGF-b1 are for the first time shown as markers of interstitial fibrosis. They are also important for making prognosis of CGN. CONCLUSION: It is shown that MCP-1 and TGF-b1 are essential for remodeling of tubulointerstitium. The urinary parameters mark TIF and can be used as criteria of activity and prognosis of CGN.


Subject(s)
Chemokine CCL2/urine , Glomerulonephritis/physiopathology , Glomerulonephritis/urine , Transforming Growth Factor beta/urine , Adolescent , Adult , Aged , Biopsy , Chronic Disease , Disease Progression , Enzyme-Linked Immunosorbent Assay , Female , Humans , Kidney/pathology , Male , Middle Aged , Severity of Illness Index , Transforming Growth Factor beta1
8.
Ter Arkh ; 78(5): 17-21, 2006.
Article in Russian | MEDLINE | ID: mdl-16889044

ABSTRACT

AIM: To estimate expression of smooth muscle alpha-actin (a-SMA) in renal glomeruli and interstitium of patients with chronic glomerulonephritis (CGN) for assessment of the disease progression and prognosis. MATERIAL AND METHODS: Expression of a-SMA in renal tissue was studied immunohistochemically, area of the interstitium and the degree of its interstitial inflammatory infiltration were investigated morphometrically in 45 biopsy specimens of renal tissue from patients with different morphological types of CGN and 7 specimens of normal renal tissue. RESULTS: a-SMA expression in the glomeruli was higher in patients with proliferative morphological forms of CGN [34.3% (26.1-40.6)] than in patients with nonproliferative nephritis forms [22.3% (18.5-22.3)], p < 0.001; it was the highest in patients with sclerotic alterations in the glomeruli [55.3% (37-61.8)], p < 0.01. The degree of a-SMA expression in renal interstitium of CGN patients correlated most closely with severity of tubulo-interstitial fibrosis (Rs = 0.08, p < 0.001). There was no significant correlation between glomerular a-SMA expression in renal biopsies and proteinuria, creatinine level in the serum of CGN patients, while a-SMA interstitial expression correlated both with severity of proteinuria (rs = 0.5, p < 0.05) and that of renal failure (rs = 0.7, p < 0.001). CONCLUSION: High expression of a-SMA in CGN occurs both in the glomeruli and interstitium of the kidney and evidences for activation of fibrogenesis but only interstitional expression can be considered as a morphological sign of CGN progression and as a factor of an unfavourable prognosis.


Subject(s)
Actins/metabolism , Fibrosis/metabolism , Fibrosis/physiopathology , Glomerulonephritis/metabolism , Glomerulonephritis/physiopathology , Kidney Diseases/metabolism , Kidney Diseases/physiopathology , Muscle, Smooth/metabolism , Chronic Disease , Disease Progression , Humans , Nephritis, Interstitial/metabolism , Nephritis, Interstitial/physiopathology , Prognosis
9.
Ter Arkh ; 77(7): 16-22, 2005.
Article in Russian | MEDLINE | ID: mdl-16116903

ABSTRACT

AIM: To study morphofunctional condition of the kidneys in patients with hematological malignancies. MATERIAL AND METHODS: Renal function, i.e. concentration ability, glomerularfiltration rate (GFR), concentration of electrolytes and beta2-microglobulin in blood serum and urine was studied at different stages of chemotherapy. Three cases are reported. All the patients have undergone transcutaneous fine-needle puncture biopsy of the kidney with histological and electron-microscopic study of biopsy specimens. RESULTS: Total urinalysis showed minimal changes. Concentration and filtration functions of the kidneys were impaired. Morphologically, glomerular damage was insignificant, there was dystrophy of tubular epithelium and focal interstitial sclerosis. Electron-microscopic examination revealed structural defects of the basal membrane of glomerular capillaries (focal thinning, focal insignificant thickening, the absence of three-layer structure at long distance) in all the patients. Dissection of the basal membrane was seen in one case. All the patients had cytoplasmic viruses: Epstein-Barr, cytomegalovirus, herpes simplex viruses type 1 and 2. In two cases mitochondria were affected with viruses. Dystrophic changes of podocytes and mitochondrial degradation were observed in all the cases. CONCLUSION: Chemotherapy may affect glomerular and tubular system of the kidney increasing probability of complications. Imbalance between cytolysis kinetics and natural clearance of the products of degradation of cells and drug metabolites may lead to nephropathy. Viral infection indicates immunodeficiency due to immunosuppression or is a direct cause of impairment of renal endothelium cells. No definite recommendations can be made still about therapeutic policy.


Subject(s)
Glomerulosclerosis, Focal Segmental/etiology , Leukemia, Myeloid, Acute/complications , Multiple Myeloma/complications , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Diagnosis, Differential , Fatal Outcome , Female , Follow-Up Studies , Glomerular Filtration Rate/physiology , Glomerulosclerosis, Focal Segmental/pathology , Glomerulosclerosis, Focal Segmental/physiopathology , Humans , Kidney Glomerulus/drug effects , Kidney Glomerulus/ultrastructure , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/pathology , Male , Microscopy, Electron , Middle Aged , Multiple Myeloma/drug therapy , Multiple Myeloma/pathology
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