Correlation between the expression of DNA topoisomerases I and IIalpha and clinical parameters in kidney disease.

Multiple factors interact during the evolution of renal diseases. In the present study, we examined the expression of DNA topoisomerases type I and IIalpha, which reflect gene transcription and DNA replication, respectively. Enzyme content was assessed by immunohistochemistry using two specific monoclonal antibodies, C21 and Ki-S4, on 81 archival punch-biopsy specimens from patients with renal diseases, including minimal change disease (MCD; n = 10), focal segmental glomerular sclerosis (FSGS; n = 6), mesangial proliferative glomerulonephritis (MPGN; n = 11), membranous glomerulonephritis (MGN; n = 10), mesangial capillary glomerulonephritis (MCGN; n = 7), rapidly progressive glomerulonephritis (RPGN; n = 12), lupus nephritis (LN; n = 15), and tubulointerstitial nephritis (TIN; n = 10). Both enzymes were strongly expressed in diseases tending to rapid progression, notably RPGN and LN, whereas MCD and MGN showed low protein levels in both the glomerular and tubular compartments. Moreover, topoisomerase expression was significantly associated with the density of monocytogenic infiltrates (monitored by means of the monoclonal antibody Ki-M1p), such pathogenesis-associated factors as antinuclear antibodies and paranuclear antineutrophilic antibodies, and serum immunoglobulin levels. There also was a positive correlation with serum creatinine levels and an inverse association with proteinuria and nephrotic syndrome. We conclude that the expression of DNA topoisomerases may be linked to pathogenetic mechanisms and may provide prognostic information. Because of their comparatively low nephrotoxicity, topoisomerase inhibitors might prove to be useful therapeutic agents in the treatment of renal diseases.

[New approaches to the treatment of nephritis]. / Novye podkhody k lecheniiu nefritov.

The paper provides evidence and results of using new therapeutical treatment of glomerulonephritis, such as pulse-therapy with cyclophosphane, therapy with angiotension-converting enzyme (ACE) inhibitors or that with antihyperlipidemic agents. Based on much experience with pulse-therapy with cyclophosphane (over 100 patients with chronic glomerulonephritis (CGN) and lupus nephritis), it is concluded that this method is highly effective. Treating 57 patients with ACE inhibitors has shown that in CGN these drugs should be used only when taking into account their antihypertensive effect and capacity of lowering intraglomerular hypertension, as evidenced by the renal functional reserve, and diminishing proteinuria. The long-term (7-12 month) antihyperlipidemic therapy (diet and lovastatin) in 20 patients with CGN accompanied by the nephrotic syndrome caused a significant reduction in the concentration of serum cholesterol and proteinuria, a significant increase in serum albumin levels; remission of the nephrotic syndrome occurred in 9 patients; but better effects were observed in non-inflammatory nephropathies, such as membranous nephropathy, focal segmental glomerulosclerosis, and nephrosclerosis.

[Disorders of intrarenal hemodynamics in glomerulopathies]. / Narusheniia vnutripochechnoi gemodinamiki pri glomerulopatiiakh.

The intrarenal hemodynamics was examined in 101 patients with chronic glomerulonephritis (CGN) and 111 patients with type I diabetes mellitus. Intrarenal hypertension was diagnosed from renal functional reserve (RFR) depletion. In CGN intrarenal hypertension was revealed in all clinical and morphological variants of nephritis: in 40% of patients with a nephrotic variant, in 25% with a latent variant and in 83% of patients with nephritis concurrent with the severe urinary syndrome. In focal segmental glomerulonephritis and fibroplastic nephritis, the depleted RFR was encountered 4 times more frequently than the preserved one. There was a association between RFR and arterial hypertension, albuminemia, blood creatinine. In diabetes mellitus intraglomerular hypertension was diagnosed in 34% of patients without renal damage (those having normal albuminuria), in 79% at the preclinical stage of diabetic nephropathy (in microalbuminuria) and in 93% at its clinical stage. Intrarenal hemodynamic disorders in diabetes mellitus are primary and provoked by hormonal metabolic disorders. The morphological signs of renal hyperperfusion failure develop at the preclinical stage of diabetic nephropathy.

[Antiviral immunity study in systemic diseases]. / Issledovanie protivovirusnogo immuniteta pri nekotorykh sistemnykh zabolevaniiakh.

The investigation of antiviral antibody titers to 8 different antigens: measles, influenza A2 and B, parainfluenza types 1, 2, 3, adenovirus and smallpox, of interferon in the blood serum, the interferon-synthesizing activity of the peripheral blood leukocytes in patients with autoimmune diseases in the period of the disease exacerbation revealed a number of immunological features. Thus, in all groups of patients antibody titers were high to measles, influenza, parainfluenza type 3 viruses, and titers of leukocyte interferon and interferon in the blood serum were 3-4-fold lower than in the control group.

[Cardiovascular aspects of systemic lupus erythematosus pathology]. / Serdechno-sosudistye aspekty patologii sistemnoi krasnoi volchanki.

The authors had 213 patients under observation with systemic lupus erythematosus. Changes in the heart were revealed in 171 patients, all had affection of the myocardium: myocarditis was found in 66 and myocardial dystrophy in 122. Appraisal of leucocyte migration inhibition with the myocardial antigen (in 23 patients) and detection of antibodies against the myocardium by immunofluorescence (in 33) suggest that disorders in cellular immunity play an important part in the development of lupus myocardial affection. Involvement of the heart in patients with systemic lupus erythematosus was partly associated with renal hypertension, which was conducive, first and foremost, to the development of myocardial hypertrophy and could be attended with increased cardiac ejection and peripheral resistance. A decrease in the cardiac output with a gradual growth in the activity of systemic lupus erythematosus was noted. Steroid myocardial affection was found in 1/4 of patients, which sometimes occurred with cardiac insufficiency and signs of inflammation. Besides mitral valve sclerosis (7%), mitral stenosis was revealed in 3 patients and aortic insufficiency in one. Echocardiography helped to make an early diagnosis of hypertrophy of the heart and pericardial effusion in patients with systemic lupus erythematosus.

[Immunomorphologic criteria of lupoid nephropathy and their value in diagnosing systemic lupus erythematosus]. / Immunomorofologicheskie kriterii volchanochnoi nefropatii i ikh znachenie v diagnostike sistemnoi krasnoi volchanki.

Immunohistochemical and electron microscopic examinations of 30 kidney bioptates from patients with systemic lupus erythematosus revealed characteristic immunomorphological features of lupoid nephropathy: glomerular immune complexes with the predominance of IgG in combination with other immunoglobulins and fibrin; subendothelial, subepithelial and mesangial depositions in d;fferent combinations found in glomerules; virus-like inclusions in the endothelium of glomerular capillaries. With these signs, the diagnosis of the lupoid nature of nephritis may be established even in those cases where the typical signs of lupus erythematosus are absent or insignificant.

[The action of cyclophosphane in different morphological variants of glomerulonephritis in mice]. / Deistvie tsiklofosfana pri razlichnykh morfologicheskikh variantakh glomerulonefrita myshei.

Heterologous serum glomerulonephritis (GN) was induced in CBA and C57BL mice. CBA mice developed diffuse proliferative GN. Glomerular changes in C57BL mice corresponded to the mesangial GN with proliferation of glomerular mesangial cells and mesangial infiltration with mononuclear phagocytes. Single administration of cyclophosphamide (CP) at the time of immunization exerted different effect on the development of the two morphological variants of GN. In CBA mice CP treatment resulted in disappearance of the immune complexes deposits with no influence on the cell reactions. In C57BL mice CP completely inhibited the development of the glomerular morphological changes. The lack of morphological similarity is most likely connected with the immunological differences in the histocompatibility complex (H-2).

[Tubulointerstitial nephropathies]. / Tubulointerstitsial'nye nefropatii.

The term tubulointerstitial nephropathy (TIN) means a renal disease, during which the tubules and interstice form a substrate of the primary injury or a substrate whose involvement is dominating in the disease clinical picture. The incidence of TIN is fairly high, with different etiology and pathogenesis. Drug, virus, bacterial and immune patterns are among the most common types of acute TIN. It is shown that the incidence of chronic drug TIN ranges from 0.2% among urban population to 0.6% among rural population. The incidence and gravity of renal injuries in hyperuricemia depend on the blood uric acid content. Study of the incidence and character of TIN in hypercalcemia in patients with sarcoidosis, hyperparathyrosis and multiple myeloma demonstrates the character of tubulointerstitial lesions to depend on the structure of paraprotein. In systemic lupus erythematosus, tubulointerstitial lesions are detected in 50% of cases. Such a comprehensive treatment of TIN opens up new vistas in the prophylaxis and therapy of this illness.

[The role of the renin-angiotensin system in the pathogenesis of nephrotic syndrome]. / O roli renin-angiotenzinovoi sistemy v patogeneze nefroticheskogo sindroma.

The state of the renin-angiotensin system (RAS) was studied in 102 patients with chronic glomerulonephritis with the nephrotic syndrome (NS) with relation to a phase of the edematous syndrome and sodium balance. Heterogeneity of patients with NS was shown with regard to RAS activity and the circulating blood volume in the whole group as well as in accumulation and stabilization phases of the edematous syndrome. A plasma renin activity value did not correlate with a degree of sodium retention permitting a review of the earlier concept of the role of RAS in sodium retention genesis during NS formation. In the phase of increment of the edematous syndrome there was definite relationship between a degree of sodium retention and glomerular filtration rate, its decrease in the initial period of NS formation being regarded as a possible factor of sodium retention.

[Acute tubulo-interstitial nephritis combined with uveitis (clinical case and review of the literature)]. / Ostryi tubulointerstitsial'nyi nefrit, sochetaiushchiisia s uveitom (klinicheskoe nabliudenie i obzor literatury).

The authors have presented a review of literature and their own data on acute tubulointerstitial nephritis combined with uveitis in a patient aged 47. In foreign literature this combination is defined as a separate syndrome (TIN-uveitis or TINU). The development of nonspecific symptoms (fatigue, weakness, nausea, loss of body mass, pains in the joints, skin rash) was characterized by change in some laboratory indices (raised ESP, anemia, eosinophilia, hyperproteinemia, hypergammaglobulinemia) and nephropathy. The signs of nephropathy were polyuria, a decrease in relative urine density, proteinuria of tubular genesis, renal glucosuria and aminoaciduria. A decrease in glomerular filtration and an increase in the level of blood serum creatinine were noted in most of the cases. In spite of the development of renal failure TINU prognosis is favorable: renal function gets back to normal by itself or after corticosteroid therapy. Uveitis shows a tendency to recurrence. The immune genesis of the TINU syndrome is assumed.