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Aim: To study expression of topoisomerases (TI) I and II alpha (DNA-bound enzymes involved in transcription and replication) in renal tissue as markers of activity and prognosis of glomerulonephritis (GN) decisive for choice of immunodepressive therapy., Material and Methods: TI expression was studied immunohistochemically in renal biopsies from 177 patients with different morphological variants of GN and in the samples of unaffected kidney tissue removed in 12 patients for local tumors., Results: There are definite differences between proliferative and non-proliferative GN variants--elevation of TI levels and monocytic infiltration in proliferative GN. Focal-segmental glomerulosclerosis is characterized by a high TI II alpha level in mesangial cells and monocytic infiltration of the glomeruli which are typical for inflammation. A statistical relationship between TI levels in mesangial cells and glomerular epithelium suggests a pathogenetic relation between these links of the pathological process. Molecular markers of activation and proliferation of cells and direct inductors of the inflammatory process (cells of monocytic infiltrate) closely correlated with the activity index--an integral indicator of inflammatory activity, as well as with the integral indicator of sclerotic processes in renal tissue--sclerosis index. Monocytic infiltration in the interstitium correlated both with morphological manifestations of activity, progression of nephritis and their clinical equivalents. In high TI expression GN resistance to immunodepressive therapy rose. To overcome the resistance, immunodepressive therapy must be more active--large doses and duration of treatment. In patients with lupus nephritis and mesangiocapillary GN renal prognosis was worse in the presence of high TI expression in mesangial cells and epithelium of the renal canaliculi., Conclusion: The authors are the first to demonstrate TI expression in renal tissue of GN patients, correlation of its level with activity of renal process as well as its role in prediction of response to treatment and the rate of renal failure progression. It is suggested that high TI expression entails a progressive course of GN.

Aim: To assess clinical implications of expression of alpha-smooth-muscle actin (ASMA) and CD34 as markers of activation and transformation of mesangial cells., Material and Methods: ASMA and CD34 expression was investigated with indirect enzyme immunoassay with addition of the complex alkaline phosphatase-antiphosphatase, mean number of stained (expressing) mesangial cells per 1 glomerulus were estimated in 47 renal tissue biopsies from patients with different morphological types of glomerulonephritis and 9 biopsies of the kidneys removed for different tumors (control)., Results: Mean expression of ASMA (11.0 +/- 3.5) was significantly higher in GN proliferative types than in non-proliferative ones and controls. In patients with proliferative nephritis ASMA expression correlated with clinical signs of nephritis activity. CD34 was expressed similarly in patients with proliferative and non-proliferative nephritis and in controls. CD34 was higher in biopsies with higher degree of sclerosis in the kidney than in the biopsies with moderate sclerosis., Conclusion: ASMA and CD34 expression by mesangial cells in renal biopsies from GN patients can be used for evaluation of the disease activity and prognosis.

Here is an observation data on systemic AL-amiloidosis with primary lesion of lungs and vessels (a false hemorrhagic syndrome, ischemic insult in the region of middle cerebral artery). At the same time lesions of kidneys and heart became of minor significance. Amiloid lesion of lungs was characterized by unusual combination of symptoms: a galloping hydrothorax, a vast focus in the consolidation of pulmonary tissue with focuses of calcification, relapsing pneumothorax.

Systemic vascular purpura (SVP) represents angiites, heterogeneous by etiology and pathogenesis. Their pathogenetic classification does not fully reflect the clinical picture, course, and prognosis. The authors suggest a clinical etiological approach to differential diagnosis of SVP. With this aim in view they examined 82 patients with SVP hospitalized at Clinic of Therapy and Occupational Diseases of I. M. Setchenov Moscow Medical Academy in 1993-1996. Etiologically-associated differences in clinical manifestations of SVP were detected and clinical etiological variants of disease were distinguished. Endotoxemia was found to be often associated with purpura of different etiology, which can be regarded as a stage in the pathogenesis. The data allow creation of a clinical etiological classification of SVP and development of new therapeutic approaches.

Aim: To determine functional fibrinolytic activity of the urine in patients with different forms of purine metabolism disorder., Material and Methods: Uricemia, 24-h uricosuria, serum creatinine, GFR, maximal urinary specific gravity, urokinase activity in the urine, total fibrinolytic activity of the urine (TFAU), activity of plasminogen activator inhibitor (PAI) in blood were studied in 33 patients with genetically determined purine metabolism disorders., Results: Patients with purine metabolism disorders vs controls had decreased TFAU and urokinase activity. There was no significant difference between the study and control groups in the levels of PAI in blood. No statistically significant difference was found between the patients with hyperuricemia and patients with hyperuricosuria in the levels of TFAU and urokinase activity, while the group with hyperuricemia was characterized by a decreased maximal specific urinary gravity., Conclusion: A decrease in TFAU and urokinase activity in patients with purine metabolism disorder was observed in the isolated hyperuricosuric stage of urite renal damage.

Aim: To assess cryoapheresis (CA) efficacy in the treatment of cryoglobulinemic glomerulonephritis (CG) with acute renal failure (ACR)., Material and Methods: Ten 34-64-year-old CG patients with associated HCV infection and symptoms of ACR (diuresis under 500 ml/day, serum creatinin 1.6-8.1 ml/dl). All the patients were examined clinically, for serum cryoglobulins, HCV, HBV markers, morphologically (renal and hepatic biopsies in 8 patients). All the patients received therapy with CA, immunodepressants. Three patients with virus replication received, in addition, antiviral drugs (alpha-interferon in a dose 3,000,000-5,000,000 IU 3 times a week intramuscularly for 6 months)., Results: CA in combined CG therapy led to fast elimination of cryoglobulins from the body, stabilization of renal function with arrest of rapid progression of renal failure, normalization of diuresis with subsequent lowering of serum creatinin. The course of CA normalized renal function fully in 3 patients, partially in 7 patients. Later, these 7 patients developed chronic renal failure. Complete elimination of the virus and remission of CG were achieved in 2 of 3 patients who had undergone the antiviral treatment for a year., Conclusion: CA can be added to combined therapy of CG aggravation as it improves renal function.

The article reviews literature and original data on renal affections associated with mixed cryoglobulinemia (MCG), discuss etiology, clinical and morphological features of renal damage, variants of the clinical course and prognosis. Among 50 patients with mixed MCG selected by the presence of cryoglobulinemia (> 100 mg/dl) and in 75% with markers of hepatitis c virus infection, renal lesion was found in 14(28%). 7 of them had moderate urinary syndrome, 4 had nephrotic syndrome and 3--acute nephritic syndrome with subsequent rapid progression. 5 patients had cryoglobulinemic mesangiocapillary glomerulonephritis. A clinical case is reported illustrating complications and difficulties of treatment of cryoglobulinemic glomerulonephritis.

Aim: Formulation of approaches to differential diagnosis and treatment policy for subacute infectious endocarditis (SIE) when it is masked by another monoorganic or systemic disease., Materials and Methods: The course of SIE was analysed in 132 patients of whom 74(56%) had erroneous admittance diagnoses. Rheumocarditis was not confirmed in 34 patients, 24 patients had nonspecific reactions masking SLE (4 cases), glomerulonephritis (7 cases), myocarditis (4 cases), hemorrhagic vasculitis, nodular periarteritis, polymyositis (9 cases)., Results: The "masks" made the SIE diagnosis more difficult, resulted in late or invalid treatment--monotherapy with steroid hormones, in particular. This complicated the diagnostic process and aggravated the disease course., Conclusion: To detect SIE it is necessary besides analysis of case record and symptoms to performe echocardiography in dynamics, because of possible late development of valvular defect. High-dose antibiotic therapy is justified for diagnosis of ex juvantibus when the diagnosis remains controversial.

Aim: To investigate clinicomorphological relationships between elevated urinary excretion of fibronectin (FN) and development of fibrosis in the kidney in patients with lupus nephritis (LN) and chronic glomerulonephritis (CGN)., Materials and Methods: Urinary FN excretion was measured at radial immunodiffusion in 54 LN patients. Of them, 15 patients had inactive LN, 39 patients had active LN varying in clinical forms. Urinary FN was also measured by passive hemagglutination in 36 CGN patients (11 inactive CGN and 25 active CGN cases). Biopsy specimens were obtained from 49 patients with active nephritis (43 with CGN and 6 with LN). FN deposits were studied immunohistochemically and morphometrically with determination of relative fibrosis area., Results: Urinary FN excretion in patients with nephritis was higher than in healthy controls. In active CGN and LN the levels of FN were significantly higher than in inactive CGN and LN. The highest FN urinary concentrations were registered in patients with severe CGN and LN, especially in the presence of renal failure and arterial hypertension. Among them, the highest individual values were observed in patients with rapidly progressive nephritis. No positive correlations were found between the degree of the urinary FN excretion increment and degree of proteinuria. This suggests local-renal origin of most urinary FN. Morphologically, FN deposits were revealed in 73% of the biopsies. In most of the patients with severe nephritis both in CGN and LN there was a diffuse distribution of FN in the glomerules and interstitium. A correlation with a morphological nephritis type was absent, but existed between FN presence in the renal biopsies and relative area of interstitium (fibrosis)., Conclusion: FN excreted in high amounts with urine in nephritis originates from the kidneys and reflects severity of fibrogenesis in the kidney.

Cryoglobulins were measured spectrophotometrically in the sera of 40 patients with renal diseases. 18 of them had chronic glomerulonephritis, 14 lupus nephritis and 8 nephritis. 20 patients with high concentration of cryoglobulins (100-600 micrograms/ml) exhibited high incidence of nephrotic syndrome (80%), arterial hypertension (90%), creatininemia (70%) and, respectively, 25, 25 and 15% of patients free of cryoglobulinemia. There was a correlation between cryoglobulins level and creatininemia (r = 0.468), proteinuria (r = 0.478), ESR (r = 0.393), systolic and diastolic arterial pressure (r = 0.393 and r = 342, respectively). An inverse relation existed with serum albumins (r = -0.526). Progression of renal failure was associated with high cryoglobulinemia. In decline of cryoglobulins content there was clinical improvement, lowering or normalization of blood creatinin levels.

A 24-year-old woman had fever with skin rash, marked hepatolienal syndrome from the age of 1.5 years followed in later life by involvement of central nervous system and kidneys. Morphologically, there was accumulation of amyloid FAP in hepatic and rectal tissues. Family history of amyloidosis and the above evidence confirmed hereditary nature of the disease.

Venous occlusion test has found out the reserve of vascular and renal endothelium in excretion of Willebrand factor in patients with inactive lupus nephritis and those with active lupus nephritis with urinary syndrome. In severe active lupus nephritis (lupus nephritis with nephrotic syndrome and rapidly progressive lupus nephritis) it was not recorded. This fact evidences intensity of immune inflammation and coagulation in the kidneys in the above forms of lupus nephritis.

60 patients with lupus nephritis (LN) were examined for frequency of thrombocytopenia, role of IgG and IgM antibodies to cardiolipin (AC), antithrombocytic antibodies (AA) and anaerobic platelet metabolism. Thrombocytopenia occurred in 28 (46.7%) patients, it was 2 times more frequent in active LN patients with AC than in those free of AC. AA were recorded in 36.6% of patients (32.2% versus 37.5% for patients with thrombocytopenia and free of it, respectively). In active LN platelet activity and metabolism became enhanced. Genesis of thrombocytopenia in various LN forms may be induced by different mechanisms.

Clinical picture, morphological changes, immunological disorders confirm reality and nosological independence of MPA. A clear nosological differentiation of systemic vasculitis is important for decision on an individual choice of treatment.

A retrospective analysis of the authors' own findings and foreign authors' data has demonstrated that neutrophilic cytoplasm antibodies (NCAs) play a definite pathogenetic role in the activation of neutrophils, a central link in the pathogenesis of vascular wall damage in necrotizing vasculitides. The clinical value of NCAs varies with their specificity. Proteinase 3 antibodies whose detection allows one to suppose Wegener's granulomatosis are of greater diagnostic value. Myeloperoxidase antibodies are revealed in various necrotizing vasculitides and promptly progressive glomerulonephritis and more infrequently in other diseases. Thus, the detection of antibodies to proteinase-3 and myeloperoxidase in the presence of appropriate clinical signs is most likely to diagnose primary necrotizing vasculitis. The changes in the levels of NCA reflect the activity of a renal processes and the progression of the whole disease.

The paper reports a rare case of 26-year-old female with diffuse infiltrative lesions in both lungs. Blood tests revealed hypergammaglobulinemia and fast ESR. Lung biopsies exhibited diffuse lymphoid infiltration with fibroatelectasis regions. Cytological and immunophenotypic studies of the lavage showed polyclonal composition of the cell population and prevalence of mature lymphocytes. The diagnosis was made of lymphocytic interstitial pneumonia (LIP). No progression of the condition was observed. In view of expected malignant transformation the case was followed up. Benign characteristics of lymphocytic infiltration, no negative shifts within 5 years allow avoiding active immunodepressive treatment in this stage of the disease which belongs to diffuse forms of pseudolymphoma and is considered to be a prelymphomatosis status.

To determine feasibility of using quantitative histochemical assessment of platelet anaerobic metabolism in lupus nephritis (LN) prognostication and elucidation of its activity, the authors examined 23 SLE patients. 20 of them developed renal lesions. Anaerobic metabolism of platelets was measured according to lactate dehydrogenase levels. All the SLE patients had significantly higher levels of the enzyme than healthy controls showed. Maximal LDG activity was registered in rapidly progressive LN with thrombocytopenia. The findings support activation of platelet hemostatic component in SLE patients and valid utilization of a new quantitative histochemical technique for determination of intracellular metabolism enzymes content.

Boyden camera tests, chemiluminescence of urinary supernatant, passive hemagglutination tests were used in measuring chemotactic properties of the urine, intensity of free-radical processes, fibronectin urine concentrations, respectively, in 31 glomerulonephritis (GN) patients. The above parameters were closely related to nephritis activity. These were much lower in patients with nephritis remission, than in subjects with nephrotic syndrome or exacerbation of latent nephritis. Chemotactic activity and intensity of free-radical processes were unrelated to protein urea which, however, correlated with fibronectin concentrations (r = 0.35, p < 0.05). The authors discuss the role of the mediators' values in evaluation of local renal inflammation and feasibility of their use as criteria of nephritis activity and prognosis.

To study humoral antistreptococcal immunity, 29 patients with acute glomerulonephritis (AGN), 211 patients with chronic glomerulonephritis (CGN) and 30 healthy donors were examined. According to EIA, blood sera of the indicated groups demonstrated antibodies (AB) to structural components of Streptococcus--A-polysaccharide (A-ps) and hyaluronic acid (HA) and to its extracellular products--streptokinase (SK) and streptolysin-O (ASLO). It has been shown that in the blood of AGN patients, the levels of AB to A-ps, SK and ASLO were high. The highest level of AB and SK was detected in 55% of the patients with the disease standing of up to half a year. In patients of all the clinical groups of CGN, the levels of AB to A-ps, SK and HA were elevated. The degree of the rise of the levels of all AB depended on the disease activity. Of prognostic importance in the chronicity of AGN and progression of CGN are high titers of AB and SK. The etiological role of streptococcus in glomerulonephritis and its importance in CGN exacerbation and prognosis are under discussion.

As many as 47 patients with amyloidosis and 31 with chronic glomerulonephritis (CGN) were examined for the blood serum content of R proteins, chemotactic activity of blood leukocytes and the degree of the inhibitory influence of the autologous serum on chemotaxis. Amyloidosis and CGN were marked by an increase of the level of receptor proteins. A reverse correlation was established between the rise of the content of R proteins and the chemotactic properties of leukocytes. In CGN, the rate of demonstration of the high titers of R proteins and the magnitude of the chemotaxis decline depended on the disease phase (the degree of activity) whereas in amyloidosis, these reactions differed insignificantly in patients with various clinical patterns and stages of renal amyloidosis.

The authors studied ++chemotaxis, phagocytosis and the activity of intracellular enzymes of leukocytes in the peripheral blood of 90 patients with reactive arthritis as compared to 23 patients with rheumatoid arthritis and 28 healthy individuals. Disorders of all these parameters were noted. They correlated with the specific features of the clinical course of the disease and its activity. In case of reactive arthritis the persistence of the infection and immunopathological disorders underlying chronic synovitis are attributable to the condition of nonspecific resistance.

Chemotaxis of cultivated fibroblasts, obtained from patients with amyloidosis, chronic glomerulonephritis and healthy volunteers, was investigated. Fibroblast migration toward donor serum and serum from patients with amyloidosis was measured using Boyden chamber's technique. As "zero" chemoattractant Hank's solution was used. It was shown, that chemotactic index (CI) was independent from cell density. Significant CI depression of fibroblasts from patients with amyloidosis toward donor serum in contrast to fibroblasts from patients with chronic glomerulonephritis and healthy volunteers was shown. The depression of chemotactic function was the same with fibroblasts from patients with different variants of amyloidosis and different stages of amyloid nephropathy and was stable in several cell generations. The results obtained suggest the existence of primary hereditary variant (variants) of chemotactic function, which may lead to the development of amyloidosis in certain conditions.