Search

Aim: A retrospective analysis of a clinical course of mesangioproliferative glomerulonephritis (MPGN) in patients with glomerular deposition of IgA (IgA nephropathy--IgA-N), with glomerular deposition of other Ig to determine prognostic factors of MpGN progression including IgA-N and to examine the patients' sensitivity to immunodepressive therapy., Material and Methods: 2000 patients with primary MPGN followed up from 1980 to 1999 from the disease onset to development of chronic renal failure (creatinine > 2.5 mg%). Factors affecting kidney survival were studied using the Cox regression model, factors predicting sensitivity to immunodepressive therapy--using multiple logistic regression., Results: IgA-N differed by the course and prognosis from other forms of MPGN. In IgA-N urinary syndrome and macrohematuria were encountered more frequently, in other forms of MPGN more frequent was nephrotic syndrome. Prognosis of patients with IgA-N was worse than in MPGN patients without IgA deposition: 10-year "renal survival" (creatinine < 2.5 mg%) was 64 and 97% (p < 0.05), respectively. Prognosis-deteriorating factors for MPGN patients were the following: male sex, nephritis onset in 40-year-olds and older subjects, acute nephritic syndrome (creatinine > 1.5 mg%), high proteinuria, hematuria (> 50 in sight), the presence of synechia and TIC in renal biopsy, location of immune deposits both in the mesangium and basal glomerular membranes. The responders to the immunodepressive therapy had 10-year renal survival 100%. Positive results of immunodepressive therapy were observed significantly more frequently in patients with normal level of creatinine, moderate hematuria, absence of synechias and TIC in renal biopsy, given large total course dose of corticosteroids and cytostatics. Efficiency of oral cyclophosphamide and its intravenous pulse-therapy did not differ significantly. In pulse therapy an average cumulative dose was lower 6 times, side effects occurred 3 times less frequently., Conclusion: The importance of morphological information for prognosis and predicting sensitivity of MPGN patients to immunosuppressive therapy necessitates renal biopsy before therapy. Intravenous pulse therapy with cyclophosphamide is preferable as an active treatment in patients with sclerosis in renal biopsy.

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.

Aim: To study gestational alterations of renal and uterine hemodynamics, their relationships with systemic and intracardiac hemodynamics in pregnant women (PW) with essential hypertension (EH)., Material and Methods: Echocardiography, ultrasound dopplerography of renal and uterine arteries, roll-over test were made in the course of trimester II-III and 3 months after the delivery in 48 PW with EH degree 1-2 and control 20 healthy PW. Hemodynamic parameters in pregnancy were compared to postpartum ones. The latter were supposed to be basal., Results: Changes in systemic and intracardiac hemodynamics in EH and control women were in many respects similar but systolic blood pressure in EH changed insignificantly, minute volume increased owing to increased heart rate. PW with EH of the second degree have in the III trimester more frequent positive roll-over test this evidencing for high pressor reactivity of the vascular system. PW with EH showed higher speed of the blood flow in the renal arteries in unchanged resistance. With growing gestation time the resistance of the uterine arteries declined. The resistance of the main stem of the renal artery went up in enhanced cardiac contraction regardless of total peripheral vascular resistance (TPVR). Blood flow in the uterine arteries worsened in elevation of arterial pressure, TPVR, lowering of the heart rate and systolic function of the heart. Renal and uterine hemodynamics were independent., Conclusion: Hemodynamic changes in control and EH PW were similar in many respects but higher arterial pressure, abnormal systolic function of the left ventricle, bradycardia disturb uterine blood flow. Renal circulation was independent of systemic and intracardiac hemodynamics and is unrelated to changes in the uterine circulation.

Aim: To characterize clinical manifestations, course and laboratory signs of nephropathy in primary antiphospholipid syndrome (PAS)., Material and Methods: 6 patients with PAS and renal affection were observed for 10 years since 1991. They were examined for anticardiolipin antibodies and/or lupus anticoagulant. Renal tissue was studied morphologically in one patient., Results: In all the patients renal damage manifested with arterial hypertension associated with isolated proteinuria. The majority of the patients had renal dysfunction. All of them had elevated level of antibodies to cardiolipin primarily in combination with lupus anticoagulant. Histological changes of renal tissue presented with thrombotic microangiopathy of glomerular and extraglomerular vessels, intimal proliferation and vascular wall thickening with occlusion of their lumen which combined with morphological indicators of focal segmental glomerulosclerosis., Conclusion: The thrombotic process in the intrarenal vessels in PAS dictates the necessity to develop novel approaches to treatment of such patients. In addition to immunodepressants the treatment should include indirect anticoagulants and antiaggregants.

Background: Circulating autoantibodies to human topoisomerases have been reported in glomerular kidney disease associated with scleroderma and systemic lupus erythematosus. However, limited information is available about the expression of topoisomerases in the kidney under normal and pathological conditions., Methods: The expression of DNA topoisomerases I and IIalpha was studied by immunohistochemistry on archival biopsies from 70 patients with chronic renal diseases. Normal kidney tissue was examined for comparison. Topoisomerase I was detected by means of monoclonal antibody (mAb) C21, and topoisomerase IIalpha was detected by means of mAb Ki-S4. In addition, mAb Ki-M1p was used to assess the density of monocytic infiltrates. All parameters were assessed in a semiquantitative manner., Results: Glomerular topoisomerase IIalpha levels were increased in mesangial proliferative glomerulonephritis (MPGN), rapidly progressive glomerulonephritis (RPGN), and lupus nephritis (LN) and were reduced in membranous glomerulonephritis (MGN), chronic transplant nephropathy (CTN), and tubulointerstitial nephritis (TIN). Tubular epithelia displayed high topoisomerase IIalpha levels in mesangiocapillary glomerulonephritis (MCGN), RPGN, TIN, miscellaneous entities (MISC) and LN, and displayed low levels in MPGN and CTN. Topoisomerase I expression was high in the glomeruli of focal segmental glomerulosclerosis (FSGS), MCGN, and RPGN and was extreme in LN, whereas it was strikingly diminished in the glomeruli of MGN, CTN, and TIN. Almost all conditions displayed lower tubular topoisomerase I levels than normal kidney, except for LN, in which the enzyme content was markedly increased. Increased glomerular monocytic infiltrates were found in FSGS, MCGN, RPGN, TIN, and LN, and tubulointerstitial Ki-M1p+ cells were seen at high numbers in MCGN, RPGN, TIN, MISC, and LN. The expression of the topoisomerases I and IIalpha was significantly correlated; also, topoisomerases showed a positive association with the density of monocytic infiltrates. The parameter profiles exhibited significant differences between distinct types of chronic renal disease., Conclusion: Topoisomerase IIalpha expression is tightly linked to cell cycling, and topoisomerase I is likely a reflection of gene transcription. Rapidly progressing glomerular disease therefore appears to be accompanied by active mesangial cell proliferation and increased metabolic activity in glomerular cells. The correlation with inflammatory infiltrates is likely to reflect a positive feedback mechanism involving cytokines, growth factors, and adhesion molecules. Assessment of topoisomerases may therefore be of diagnostic help and might allow prognostic predictions. Provided that our observations are supported by clinicopathological follow-up studies, one might envisage the use of topoisomerase inhibitors in the therapy of chronic proliferative renal disease refractory to current treatment protocols.

This review considers molecular mechanisms that underlie disorders in the structure and metabolism of renal extracellular matrix in diabetic nephropathy. The contribution of the increased synthesis of renal extracellular matrix proteins in the accumulation of renal mesangial matrix is considered, and the important role of the degradation system of the extracellular matrix proteins in the development of fibrosis is also shown. Data on changes in mRNA expression for the matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) in various forms of diabetic nephropathy are presented. A correlation is established between changes in the balance of MMP proteolytic activity and TIMP activity and the accumulation of extracellular matrix.

Aim: To evaluate effects of pregnancy on the course and prognosis of lupus nephritis and fetal outcome, in particular, in patients with lupus nephritis (LN) and antiphospholipid syndrome (APS)., Material and Methods: A retrospective analysis was made of the course of LN in 31 females (44 pregnancies)., Results: A favorable outcome of pregnancy is possible in LN women if they had a persistent remission at conception. However, one third of these women had exacerbations of LN in pregnancy and early postpartum period. Pregnancy developing in active LN aggravated LN course in all the women. Fetal outcome was unfavorable. LN was especially severe if it arose in the course of pregnancy or early postpartum period. It seems that the presence of APS affected pregnancy outcome in a less degree than LN activity., Conclusion: Both in pregnancy and postpartum period, LN showed frequent exacerbations, but if the conception takes place during a persistent remission of LN, under adequate care and treatment, a delivery of a viable child is possible without an extraordinary risk for the mother.

Aim: To retrospectively analyze clinical course and results of immunodepressive therapy of patients with primary focal-segmental glomerulosclerosis (FSGS), to reveal prognostic factors of the disease progression and patients' sensitivity to immunosuppressive therapy., Material and Methods: Morphological diagnosis was specified, morphological indices of activity and sclerosis were estimated, renal survival was analysed, mono- and multivariate analysis of prognostic factors was made by the evidence obtained in the study of 135 biopsy specimens from CRF patients meeting the criteria of FSGS., Results: At the moment of the disease onset only age of the patients was related to FSGS: 5- and 10-year survival was 100% if the disease started under 16 years of age, if older--the survival was 80 and 65%, respectively. Nephrotic syndrome, hematuria, high creatinine, racemose alterations in the glomeruli worsened the disease prognosis. When cytostatics and corticosteroids were used in combination they produced better results and were associated with better prognosis than each of them in monotherapy. Patients with marked hematuria and low proteinuria were less sensitive to therapy than those with weak hematuria and high proteinemia. Patients with FSGS having high IA and SI required more aggressive therapy for response., Conclusion: Renal biopsy with quantitation of IA and IS increases the prognosis accuracy and is important for choice of the treatment policy in patients with primary FSGS.

Aim: To evaluate platelet dysfunctions and pregnancy outcomes in females with gestational exacerbation of chronic glomerulonephritis (CGN) and the disease remission., Materials and Methods: Platelet metabolism was studied by activity of intraplatelet LDG, platelet secretory activity by plasm beta-TG and ADP-aggregation in 75 gravidae. Of them 16 had exacerbation of CGN, 40 females were in remission of CGN and 19 healthy pregnant women served control., Results: Enhanced LDG activity and intensity of maximal ADP aggregation, high beta-TG levels compared to control were recorded in gravidae with CGN both in exacerbation and remission. The frequency of preterm deliveries, intrauterine growth retardation, neonatal hypotrophy was greater in women with gestational exacerbation of nephritis compared to pregnant women with stable nephritis., Conclusion: Metabolic and functional platelet hyperactivity with platelet intravascular activation in pregnancy in aggravated CGN suggest contribution of platelets to onset of the disease gestational exacerbation. Pregnancy-induced overactivation of platelets in CGN exacerbation stimulates intravascular coagulation in placental circulation with resultant microthrombi in placental vessels responsible for high rate of unfavorable pregnancy outcomes in relevant patients.

Aim: To investigate the relationship between polymorphism of angiotensin-converting enzyme (ACE) gene and predisposition to chronic glomerulonephritis (CGN) as well as antihypertensive and anti proteinuric response to ACE inhibitors (ACEI) treatment, therapy with angiotensin II receptor antagonists., Materials and Methods: Genotype was determined in 57 CGN patients and 113 subjects free of chronic diseases. Effects of ACE gene polymorphism on antihypertensive and antiproteinuric efficiency of ACEI and cozaar were studied in 35 CGN patients on monotherapy. 24-h proteinuria, levels of creatinine, potassium in the serum, arterial pressure, glomerular filtration rate were measured in all the patients., Results: No significant differences were found between incidence of ACE gene genotypes and alleles in patients with CGN and controls. Maximal antihypertensive response to therapy was observed after a month treatment in patients with genotypes II and ID. Lowering of arterial pressure in patients with genotype DD was observed on month 6-12 of continuous therapy. Proteinuria diminished on the treatment month 1-3 in patients with genotypes II and ID, in genotype DD proteinuria rose for the same period of time. Proteinuria dropped similarly in all the groups by month 6-12., Conclusion: Relations between ACE gene polymorphism and genetic predisposition to CGN were not found. Patients with genotype II were most sensitive to IACE and cosaar treatment. Lack of an early anti proteinuric response in homozygotes DD does not determine effectiveness of long-term IACE treatment and should not be a reason for the above drug discontinuation.

Aim: To study the role of abnormal intrarenal hemodynamics (IRHD) in progression of lupus nephritis (LN) and its response to therapy with inhibitors of angiotensin-converting enzyme (ACE)., Materials and Methods: The trial included 30 LN patients (27 females, 3 males; age 29.8+(-)10.4 years). 19 had aggravation of active LN. All the patients were free of chronic renal insufficiency. IRHD was studied with estimation of renal functional reserve (RFR) using protein loading, evaluation of clinical activity of LN and renal function, blood pressure. The tests were repeated after 6 months of treatment with ACE inhibitors (captopril and ramiprilol) in 13 patients (11 of them had exacerbation of active LN)., Results: Disturbed IRHD was found in 37% of the patients. Blood hypertension deteriorated this condition. Treatment with ACE inhibitors in 6 months brought about a significant decrease in blood pressure and improvement of IRHD. Before treatment RFR was absent in 46% of patients, after treatment in 1 patient., Conclusion: Defects in IRHD occur in LN frequently. These are related with the presence of blood hypertension and activity of LN. Inhibitors of ACE seem perspective in management of essential hypertension in LN patients but this hypothesis needs confirmation by the results of further studies.

Aim: Comparison of two cyclophosphamide (CPA) treatment regimens in chronic glomerulonephritis (CGN) patients: oral daily CPA versus intravenous CPA pulses (IV-CPA) MATERIALS AND METHODS: 31 nephrotic patients entered the trial: 12, 16 and 3 with membraneous, mesangial proliferative and mesangiocapillary CGN, respectively. The patients were randomized into two groups. 13 patients of group 1 received oral CPA (1.5-2.0 mg/kg/day for 6 months, while 18 patients of group 2 received IV-CPA pulses (20 mg/kg/monthly, at least 6 pulses) combined with oral prednisolone (40-6-mg/day during 1.5 mo with subsequent tapering). At entry, no statistical differences (p > 0.05) were found between groups 1 and 2 by age, gender, duration of the renal disease, serum creatinine levels, frequency of arterial hypertension. Mean duration of follow-up was 27.6 and 22.6 mo (p > 0.05) for group 1 and 2, respectively., Results: After 6 months of follow-up there was no difference in the rate of complete and partial remission between the groups (69 and 83% for group 1 and 2, respectively). The rate of renal function deterioration was also similar. Side effects occurred 3 times more frequently in group 1 than group 2. The mean cumulative course dose of CPA per 1 patient in group 1 was 35.6 g, in group 2--5.6 g., Conclusion: The effectiveness of methods was similar irrespective of CGN morphological form, but in spite of similar rates of remission of nephrotic syndrome, pulse CPA is preferable being more safe as to possible complications.

Incidence of arterial hypertension (AH), its relation with activity of lupus nephritis (LN), other factors (antiphospholipid syndrome, old age, disturbances of purin and lipid metabolism), prognostic implication of AH were studied in a trial performed from 1957 to 1996. A total of 398 patients with LN were divided into 3 groups according to immunosuppressive therapy practiced in different time periods. Overall AH incidence and that of severe AH were similar at present and in the past. AH occurred frequently in patients with rapidly progressing LN and active LN with nephrotic syndrome. In remission of nephrotic syndrome AH incidence was on the decrease. This suggests that hypertension may be a criterion of LN activity. AH was also associated with the presence of antiphospholipid syndrome and old age. AH was a separate prognostic indicator in respect to overall and renal survival. Hemodynamic mechanisms may contribute to LN progression.

Sandimmun was given to 11 patients (7 males and 4 females) aged 16-34 years with chronic glomerulonephritis (CGN) and nephrotic syndrome (NS). Various morphological forms were revealed: minimal changes (MC), focal-segmentary glomerulosclerosis (FSGS), mesangiocapillary glomerulonephritis (MCGS), membraneous glomerulonephritis (MGN), mesangioproliferative glomerulonephritis (MPGN). They occurred in 1, 3, 2, 1 and 3 patients respectively. Biopsy was not made in 1 case. The duration of the disease varied from 1 to 4 years. Prior to this therapy 10 patients failed corticosteroids and cytostatics. Hypertension, high creatinine were registered in 3 and 5 patients, respectively. Sandimmun was given for 2-18 months in a daily dose 3-5 mg/kg. Serum concentration 70-180 ng/ml. After 1 to 18 months of treatment nephrotic syndrome relieved in 1 MGN, 3 MPGN, 2 FSGS, 2 MCGS patients. The recurrences were reported in 4 patients after the drug discontinuation. Serious complications were absent.

The activity of NO-synthase and formation of NO (EDRF) were assessed by an increase in the activity of NO-dependent hyanilate cyclase in response to L-arginine in vitro in platelets of 61 pregnant females (39, 8 14 with essential hypertension, preeclampsia and healthy controls, respectively) and in 9 hypertensive nonpregnant females. Compared to healthy pregnant females, EDRF synthesis activity was inhibited in hypertensive gravidas but enhanced in preeclampsia patients. Effectiveness of exogenic donator NO (transdermal nitroglycerine, Nitroderm NNS 5) was studied in a randomised trial of 76 gravidas with essential hypertension (EH), EH and chronic glomerulonephritis (GN). 39 of them were given transdermal nitroglycerine, 37 received acetylsalicilic acid and curantil. The number of treatment failures was the same in both groups. The conclusion is made that nitro compounds are adequate for use in EH and chronic GN gravidas.

Review of the literature and case report concern renal damage in hereditary osteo-onychodysplasia (nail-patella syndrome). This syndrome is a rare genetic disease inherited by the autosome-dominant type. It arises because of underdevelopment of tissues of mesodermal and ectodermal origin and is characterized by hypoplasia or absence of patella, ulnar dysplasia, nail plate dystrophy, growths on the iliac bones, renal affection. The disease was detected in early childhood. Renal affection presented with urinary syndrome with a concurrent nephrotic syndrome later on followed by moderate arterial hypertension and progression to renal failure. Renal biopsy revealed the picture of focal segmentary glomerular hyalinosis typical for this disorder. Because immunodepressants were thought inadequate, the treatment included lovastatin and inhibitors of angiotensin-converting enzyme to inhibit non-immune mechanisms of the disease progression.

To assess platelet changes in pregnant women with chronic glomerulonephritis (CGN) and essential hypertension (EH) we estimated platelet lactic dehydrogenase activity (LDH), beta-thromboglobulin and thromboxane B2 (TxB2) plasma levels and ADP-stimulated platelet aggregability. Five groups of gravidae (26-40 weeks of gestation) were studied: with EH (n = 20), with CGN and hypertension (n = 31), with CGN without hypertension (n = 29), with late toxemia (n = 11), nonpregnant CGN women (n = 10) and healthy pregnant women (n = 20). Activation of platelet function was found in gravidae with CGN and EH. Platelet disorders were especially pronounced in pregnant women with CGN and with EH, but they were less pronounced than in control group with late toxemia. We believe that hypertension is more important stimulating factor for platelet activation than renal disease. We suggest that platelet disorders in outpatients are brought about by endothelium damage caused by elevated blood pressure.

ELISA was used to measure tissue plasminogen activator antigen in blood plasma and urine of 42 patients with active lupus nephritis (16 with isolated urinary syndrome, 13 with nephrotic syndrome, 13 with rapidly progressive LN). Control groups consisted of 17 patients with inactive LN and 15 healthy subjects. Inhibition of fibrinolysis in vascular system correlating with the disease severity was found in patients with active LN. This may result from both defective synthesis of tissue plasminogen activator and neutralizing action of antiactivator. Urinary fibrinolytic activity was inhibited only in patients with rapidly progressive LN because of hyperactive synthesis of antiactivator. The above changes occur as endothelial cell dysfunction due to activating and damaging action of immune complexes, antibodies, cytokines on vascular endothelium. Zero activator activity of plasma and urine in patients with active LN reflects severe dysfunction of endothelial cell caused by its structural disorganization.

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.

The treatment with inhibitors of angiotensin-converting enzyme (ACE) was conducted in 57 patients with chronic diffuse renal diseases. Of them 45 patients received Capoten, 12 patients Renitek. ACE inhibitors were examined for effects on arterial pressure, proteinuria, renal and intrarenal hemodynamics. A hypotensive effect was apparent in hypertension and minimal in normotension. One month later renal bloodflow increased, glomerular filtration rate did not change. ACE inhibitors proved able to correct intrarenal hypertension: renal functional reserve returned to normal on posttreatment month 1-3 in 10 of 16 patients. Noticeable antiproteinuria effect of the drugs emerged 3 months after the treatment.

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.

Inhibition of non-immune progression of renal insufficiency for control of glomerulonephritis was attempted via hemodynamic, metabolic and hypolipidemic means. Hemodynamic correction was conducted using inhibitors of angiotensin-converting enzyme capoten and renitek. The action on metabolic factors of progression was realized by lovastatin mevakor. Capoten and renitek exhibited in 57 patients with chronic nephritis not only a hypotensive effect, but also reduced intraglomerular hypertension and proteinuria. A long-term (7-12 months) hypolipidemic therapy (diet and lovastatin) in 20 patients with chronic glomerulonephritis with nephrotic syndrome resulted in lowering of serum cholesterol concentrations and proteinuria, raised serum albumin. 9 patients achieved remission of nephrotic syndrome. The highest effect occurred in non-inflammatory nephropathy: membranous nephropathy, focal-segmental glomerulosclerosis, nephrosclerosis.

In view of weak implication of immunoinflammatory mechanisms in pathogenesis of noninflammatory nephropathy one may expect the disease course improvement and more slow progression of renal dysfunction. The mechanism of this action can be realized through hypolipidemic effect. In recent research there are data on a direct lovastatin action on the mechanism underlying nephritis progression by means of inhibiting proliferation of mesangial cells.

Time course of 187 pregnancies was followed up in 103 females with chronic renal diseases (CRD), 76 females with essential hypertension (EH) and 14 posteclampsia females. Three variants of arterial pressure (AP) and 5 types of proteinuria changes were recognized in CRD and EH patients. The pattern of these changes was compared to that in posteclampsia patients, the eclampsia being an absolute criterium of late toxicosis. It is shown that neither elevated AP and proteinuria nor their absolute values can serve reliable signs of late gestosis in CRD and EH patients. Only the trend in these parameters is significant. CRD and EH females with late gestosis exhibit rapidly growing proteinuria in line with the onset or exacerbation of EH. Retrospective analysis of the pregnancies has confirmed association of late gestosis in 15% of EH and 7% of chronic glomerulonephritis patients. These estimates are lower than commonly accepted. Early diagnosis of late gestosis in pregnant females with CRD and EH requires not only regular AP registration, but also dynamic, in some cases hourly, evaluation of proteinuria.

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.

Sandimmun (ciclosporin A) treatment of chronic glomerulonephritis with nephrotic syndrome in a dose 2.5-5 mg/kg for 6-10 months relieved nephrotic syndrome in 2 and resulted in clinical improvement in other 2 of 4 patients treated. In 3 cases the patients failed previous therapy with high-dose corticosteroids and cytostatics. The drug reduced proteinuria, elevated serum levels of albumin and total protein, had low nephrotoxicity.

A venous occlusion test was used to evaluate the reserves of the kidneys and that of vascular endothelium fibrinolytic activity (VEFA) in patients with lupus nephritis (LN). Prior to and following venous occlusion functional activity of plasminogen activators in plasma and urine (PAPU), plasma activity of antiactivator (PAAA), urokinase urine activity (UUA) were measured by fibrin plate lysis test in 24 patients with active LN, 6 SLE patients with intact kidneys, 10 healthy subjects. Venous occlusion test revealed normal reserve of plasma activator activity in mild LN and depletion of this reserve in LN patients with nephrotic syndrome and rapidly progressive LN. In the latter patients PAPU and PAAA were suppressed. PAPU reserve existed in all the patients, but those with rapidly progressive LN. UUA in LN was close to normal and did not change significantly after venous occlusion. The data obtained suggest that patients with severe LN had reduced reserves of VEFA, while in those with progressive LN there were also diminished reserves of renal fibrinolytic activity reflecting the severity of endothelial lesion.

A study was made of diagnostic significance (sensitivity and specificity) of early (precritical) signs of late gestosis (LG). A total of 179 females (187 pregnancies) with essential hypertension (EH) and chronic renal diseases (CRD) were examined. EH women are at high risk of LG when they have proteinuria above 0.3 g/s, of relative prognostic importance are severe hypertension and marked hyperuricemia. Severe hypertension, fetal growth inhibition, positive roll-over test may indicate LG in CRD. Primiparas with EH or CRD are especially at risk of LG. As all the above LG signs in its precritical stage are not specific and indicate only probability, they can be used primarily for screening of patients with high risk of LG onset. The diagnosis of LG in EH and CRD should be based on follow-up changes in the clinical and laboratory indices.

A SLE course has been analyzed retrospectively in pregnancy and after delivery for 34 patients (44 pregnancies). Aggravation of the disease was registered in 6 cases (13.5%). Only two of them received prophylactic corticosteroid maintenance. Two SLE patients with unaffected kidneys had no pregnancy-related SLE exacerbations though they developed nephropathy of the pregnant. After delivery the disease aggravated in 12 patients (27.3%). Five patients had moderate exacerbations within half a year after the delivery, seven patients developed severe exacerbations within 3-11 postnatal months. Five out of seven women presented nephrotic syndrome. One of the patients died of rapidly progressive glomerulonephritis. Three women had renal damage after the delivery as initial condition. SLE exacerbations were reported more frequently in young patients (under 30, in 15 of 31 pregnancies) than in older ones (over 30, in 3 of 13 pregnancies). Postnatal SLE aggravations can be prevented by large doses of prednisolone (20-30 mg/day) administered for 2-3 weeks.

Pregnancy complications have been analyzed in 124 females suffering from essential hypertension (EH) and chronic glomerulonephritis (CGN). Such complications, as late gestosis (8.9%), ablation placentae (1.6%), premature delivery (14.5%), intrauterine growth retardation (14.5%) occurred more frequently than in population. Pre- and perinatal deaths were encountered with the same frequency as in the population. Morphologically, the placentas had in many cases histological evidence of moderate placental insufficiency (PI). In more than 60% of the patients there were uteroplacental and fetoplacental hemodynamic defects. Placental circulatory disorders and PI ran subclinically in most of the cases as they were compensated. In EH and CGN pregnant women, compared to healthy controls, red cells acquired abnormal forms more frequently, serum thromboxane B2 levels got elevated, lactate hydrogenase activity became enhanced. Erythrocytic damage and platelet activation in EH and CGN pregnant women may indirectly confirm the existence of systemic angiopathy. It is suggested that ischemic placenta may produce endothelial toxin, that systemic endothelial damage in EH, CGN, PI may be synergetic which potentiates its clinical appearance in the form of the above pregnancy complications.

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.

A fibrin plate technique was employed to study functional activity of plasminogen activators in plasma and urine (FAAP, FAAU), activity of antiactivator in plasma (AAAP), urokinase urine activity (UUA) in 35 lupus nephritis (LN) patients. The latter comprise 3 groups by the disease severity: 22 patients with active LN attended by urinary syndrome (group 1), 7 patients with LN associated with nephrotic syndrome (group 2), 6 patients with rapidly progressing LN (group 3). Control groups included 5 SLE patients with unaffected kidneys and 25 healthy subjects. FAAP proved heterogeneous both in SLE and healthy subjects. SLE patients with progressive LN had diminishing FAAP which was accompanied by growing AAAP. The latter reached maximal values in groups 2 and 3. UUA declined with LN aggravation. The relation of low FAAP in LN patients to affection of vascular endothelium and binding of plasminogen activators with the inhibitors to form inactive complexes is considered.