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In most countries glomerulonephritis is the second most common cause of the end-stage renal disease, after diabetic nephropathy in renal replacement therapy programs. Occurence of primary glomerular diseases in young and middle aged patients, in whom they restrain their lives and professional careers, results in their particular position among causes of replacement therapy. A highly important component of the therapeutic approach to nephrotic patients is appropriate symptomatic treatment. Proteinuria reduction is crucial in the prevention of progressive kidney function decline in the course of glomerulonephritis. A long-term therapy of glomerulonephritis should be conducted both by the general internal medicine specialist and the nephrologist. The treatment with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers can be performed by the internist, but the immunosuppressive programs should be initiated and supervised by the nephrologist.

Thanks to a precisely regulated response, the immune system works to maintain homeostasis, and one of the significant mechanisms of this regulation is regulatory T cells. This paper presents the latest knowledge concerning the occurrence of natural regulatory T cells of CD4+CD25+ phenotype and their role in the pathogeneses of immune system diseases. Functional and quantitative disorders in this population of cells are found in many diseases which in their course attack the kidney, for instance mixed cryoglobulinemia, rheumatoid arthritis, Sjögren's syndrome, lupus erythematosus, and type 1 diabetes mellitus. The role of T cells and the effectory and regulatory mechanisms dependent on them in the development and progression of glomerulonephritis is presented. The role of regulatory T cells in the development and progression of chronic kidney disease is discussed as well. Qualms whether a decreased number and/or disrupted function of regulatory T cells promote the development of autoimmune diseases or whether they are secondary phenomena are settled by clinical observations in which restoration of the number of the cells prevents further tissue damage. Strengthening or blocking regulatory T-cell functions and obtaining a balance between activation and suppression in the immune system depending on current needs may become the key to the immunotherapy of many diseases. Another problem presented in this paper is the perspective of regulatory T cell therapy; however, attempts to modify their activity and change the number of cells must be carried with the greatest of care because such a procedure may result in dysregulation of the immune system.

Glomerulonephritis are known to be associated with cancer disease. Although these association is well documented but the number of conditions must be fulfilled to establish a causal relationship between the malignancy and glomerulopathy. Secondary membranous glomerulonephritis is relatively often noted type of glomerulopathy, but other types have been mentioned, especially IgA nephropathy, minimal-change disease, rapidly progressive glomerulonephritis and anti-GBM disease in the case of neoplastic obstruction of urinary tract. The most frequent types of malignancies are pulmonary, renal and gastrointestinal solid tumours. The pathogenesis is immunological due to the involvement of tumor associated antigens, re-expressed fetal antigens, and/or viral antigens. Immune complexes (circulating or formed in situ) containing tumor-associated antigens are suspected of causing glomerular injury. The diagnosis of malignancy may be established either before, concomitant or after the development of nephrotic syndrome. Slow remission of nephrotic syndrome is sometimes observed after resection or successful treatment of the tumor, and relapse has been reported during the relapse of cancer. The non-specific treatment of nephrotic syndrome is recommended and the immunosuppression generally should be avoided because this may exacerbate the malignancy. Sometimes also antiviral therapy can be considered. Patients with nephrotic syndrome due to membranous glomerulonephritis, aged over 50, should be carefully screened for malignancy. The tumor prognosis determines patient outcome.

Background: High urinary excretion of lysosomal enzymes is thought to reflect tubulointerstitial damage and is observed both in the acute and chronic phases of various morphological forms of glomerulonephritis (GN). It is related to the degree of proteinuria and secondary interstitial inflammatory process. N-acetyl-beta-D-glucosaminidase (NAG) and beta-glucuronidase (beta-GR) are the most commonly used markers of tubulointerstitial injury. NAG and beta-GR are also contained in azurophilic granulations of polymorphonuclear leukocytes (PMNs) and may be released during the activation of PMNs., Aims: The aim of this study was to elucidate the role of PMN degranulation in causing the increase of urinary excretion of lysosomal enzymes that is observed in glomerulonephritis., Material and Methods: We analyzed the urinary excretion of NAG, its B isoenzyme NAG-B, beta-GR and leukocyte elastase (EL), in 91 patients with morphologically different primary and secondary glomerulopathies, and in 12 healthy controls., Results: Excretion of NAG, NAG-B and beta-GR were statistically significantly higher in all GN patients in comparison to healthy controls. In the whole analyzed GN population significant correlations between amount of proteinuria and excretion of NAG, NAG-B and beta-GR were ascertained. In subgroup analysis NAG excretion was significantly correlated with proteinuria in patients with diffuse proliferative GN (PGN), mesangiocapillary GN (MCGN), and minimal change disease (MCD). There was a significant correlation between NAG-B and proteinuria in MCD and PGN patients. There was a significant relationship of beta-GR and EL with proteinuria and EL with NAG in the PGN group. Significant relationships between serum creatinine and excretion of EL but not NAG, NAG-B, or beta-GR were observed in the whole examined group., Conclusions: Increased urinary excretion of elastase, with concomitant high proteinuria and NAG excretion in patients with proliferative GN may indicate that leukocyte degranulation is an additional source of enzymuria in the primary i.e. glomerular inflammatory process. Significant relationship between EL excretion and serum creatinine may indicate that EL released from PMN may also participate in the secondary i.e. interstitial injury that is decisive in the progression of GN.

We analysed the occurrence of anti-neutrophil cytoplasmic antibodies (ANCA) in sera of 191 patients with glomerulonephritis (76 females and 115 males) by the standard indirect immunofluorescence method (IIF). The presence of ANCA was demonstrated in sera of 4.4% (8/181) patients with idiopathic glomerulonephritis (GN) and in 30% (3/10) of patients with rapidly progressive glomerulonephritis (RPGN), as a form of renal limited vasculitis. In the experimental part of our study we analysed the influence of GN ANCA-negative sera on the neutrophil function in vitro and compared with the effect of ANCA-positive sera (titre > or = 4:40) from systemic vasculitis (SV) patients with renal involvement. The activation of neutrophils was established by reactive oxygen species (ROS) production and the ability of superoxide anion to reduce ferrocytochrome c. Among 30 ANCA-negative GN sera 20% (6/30) revealed the ability to activate neutrophils isolated from healthy donor. Remaining ANCA-negative GN sera and all sera from normal healthy individuals (negative control group) did not affect the neutrophil function and did not induce the superoxide anion production. Their effect was similar to the second negative reference system without serum. Only 33% (3/9) of high titre ANCA-positive sera (> or = 1:40) from SV patients were able to activate neutrophils and to produce the superoxide anion with following ferrocytochrome c reduction, but the effect of activation was most powerfully expressed (three times greater than by GN ANCA-negative sera). The remaining ANCA-positive sera and all SV ANCA-negative sera did not affect the neutrophil function in vitro. These experimental data indicate that the presence of ANCA in GN sera is not necessary to induce neutrophil activation in vitro. On the other hand the influence of the SV ANCA-positive sera was most powerful expressed, although only 33% of sera were able to activate neutrophils in vitro. Our results indicate that not always ANCA presence in serum was connected with the ability to neutrophil activation in vitro. It is possible that in ANCA-negative sera other factors were able to activate neutrophils in vitro, but the effect of activation was markedly lower.

Background: Some preliminary observations suggest that predisposition to a particular type of glomerulonephritis (GN) may be connected with the genetically determined charge of the glomerular capillary wall. A correlation between erythrocyte surface and the glomerular capillary wall charges has also been observed. The purpose of this study was to verify and extend previous investigations. Therefore we measured erythrocyte and platelet surface charge from patients with idiopathic membranous and mesangial GN as well as idiopathic membranoproliferative GN and lupus nephritis., Methods: The erythrocyte and platelet surface charge was determined by the binding of the cationic dye, alcian blue (AB). A fresh alcoholic AB solution was made for each experiment, which were run in batches of four, each including cells from a healthy person and from patients each with a different type of GN., Results: In patients with idiopathic membranous and membranoproliferative GN, a significant decrease in the erythrocyte and platelet charges was observed irrespective of their clinical state (remission or nephrotic syndrome). Erythrocyte charge was decreased despite the normal amount of membranous sialic acid. In contrast, patients with idiopathic mesangial GN, in complete or partial remission, exhibited normal erythrocyte and platelet surface charges. Exclusively in this type of GN, the appearance of nephrotic proteinuria was associated with a slight decrease, the erythrocyte charge, which was not statistically significant (P > 0.1). A reduction in the negative erythrocyte charge in lupus nephritis was less in magnitude than in idiopathic membranous or membranoproliferative GN, and occurred independently of the level of daily proteinuria, whereas the platelet charge was normal., Conclusion: The decrease of the erythrocyte and platelet charge in idiopathic membranous and mebranoproliferative GN seems to be a pre-morbid feature.

In the present study influences leading to in vitro formation of dysmorphic erythrocytes were studied. Fresh and surface altered erythrocytes pretreated with several proteases were passed through different solutions representing distinct nephronís fluids. After passage of intact erythrocytes only 12-15% dysmorphic cells were observed. In case of protease treated cells the number of dysmorphic cells rose to 35-80%. The hemoglobin content was decreased. PAGE and electron microscopical findings demonstrated substantial losses of transmembrane and membrane skeleton proteins. It is assumed that surface protein degradation, loss of membrane skeleton proteins and hemolysis seem to be closely associated with dysmorphic malformation of urinary erythrocytes characteristical for glomerulonephritis.

Tests on blastic transformation of peripheral blood lymphocytes after stimulation with nonspecific mitogens (PHA, Con A, PWM) were performed on 55 patients suffering from glomerulonephritis and 32 persons belonging to the control group. On the basis of results obtained, the patients with glomerulonephritis were divided into three groups. The first, comprised patients with acute proliferative glomerulonephritis in whom the values of blastic transformation after stimulation by three mitogens used did not differ from the control group. The second, comprised patients with chronic proliferative, membraneous-proliferative, and membraneous glomerulonephritis. In 1/3 of them, a decrease blastic response to one of three mitogens was observed which was most often connected with stimulation by Con A. The third group comprised patients in the active phase of submicroscopic glomerulonephritis and lupus nephritis showing the lowest values of blastic transformation. The estimation of mitogen-induced blastic transformation was repeated in 17 patients after several weeks of nonsteroid anti-inflammatory drug therapy. After the treatment, values of spontaneous blastic transformation decreased statistically significantly. The mean values of mitogen-stimulated blastic transformation were also lower after the treatment, but the difference was not statistically significant.

Studies on the adenosine deaminase (ADA) and aldolase activities in lymphocytes were performed in 67 patients with glomerulonephritis (gn) and in 20 healthy individuals from the control group to get an insight into the lymphocyte metabolism. Statistically significant decrease of ADA activity was found in the groups of patients with chronic proliferative gn, membranoproliferative gn, membranous gn and lupus nephritis in comparison with the healthy individuals from the control group. As far as decrease of aldolase activity is concerned it has reached statistical significance in patients with mesangial gn, membranoproliferative gn, membranous gn and lupus nephritis. The lymphocyte metabolism did not show any abnormalities in the enzymatic indicators only in patients with acute proliferative gn and submicroscopic gn. The activity comparison between both enzymes in the lymphocytes, contrasted on the basis of high and low clinical dynamics of gn, revealed a tendency to lower ADA and aldolase activities in patients with high clinical dynamics. However, this difference was at the limit of statistical significance (p less than or equal to 0.10).

Lymphocyte suppressive activity after stimulation with Con A and lymphocyte function as the effectors in the ADCC test had been examined in 68 patients with chronic glomerulonephritis (GN) and in 20 healthy controls. Lymphocyte suppressive activity was lower in patients with chronic GN than in the healthy individuals. In regard to chronic proliferative GN and mesangial GN the difference was statistically significant. The lymphocyte efficiency in the ADCC test was generally adequate in patients with chronic GN and none of the morphological types showed significant deviation from the control group. In the general analysis of patients with chronic proliferative, mesangial, membrano-proliferative and membranous GN a decrease of lymphocyte suppressive activity below the lower standard limit has been detected (45% of cases). A similar defect in lymphocyte function in the ADCC test has been found in 18.6%. A statistically significant relationship between the lymphocyte function disorders and the high clinical dynamism of GN has been noticed, although in some cases there was a deviation from this tendency. It is supposed that circulating immune complexes, detected in some patients with chronic GN are not the only decisive factors responsible for defects in lymphocyte function.

In vitro reactivity of lymphocytes to phytohemagglutinin (PHA) and pokeweek mitogen (PWM) was studied in 17 patients with chronic glomerulonephritis treated systematically over many months (average, 23 months) with immunosuppressive drugs (prednisone, indomethacin, azathioprine, cyclophosphamide). Blastic transformation of lymphocytes in cultures stimulated with PHA was tested three times: before beginning of treatment, during the course of therapy with full doses, and after prolonged ambulatory treatment with maintenance doses. The degree of blastic transformation under the influence of PWM was determined only after periods of many months of treatment with chemical immunosuppresors. The results showed that neither treatment of chronic glomerulonephritis for several weeks with full doses, nor subsequent prolonged administration (for periods of tens of months) of maintenance doses of immunosuppresors regularly inhibit blastic transformation of lymphocytes stimulated with PHA. Similar observations were made using PWM after many months of immunosuppressive therapy. Reactivity of lymphocytes to PWM in all patients resembled reactivity to PHA.

Studies were performed on 79 subjects, out of which 32 belonged to the control group and 47 suffered from glomerulonephritis. The number of T and B lymphocytes in peripheral blood was determined using the technique of E, EA and EAC-rosette tests. Also, the lymphocyte blast response to non-specific mitogens (PHA, Con A, PWM) was established in vitro. Patients suffering from acute proliferative glomerulonephritis, as compared to the control group, displayed a statistically significant increase of lymphocytes with the receptor for complement (EAC-rosettes). Their reactivity to all three mitogens did not differ from the values obtained in the control group. In patients suffering from chronic glomerulonephritis (proliferative, membranous-proliferative, membranous), shiftings in the contents of the peripheral blood lymphocytes pools were of opposite directions, i.e., statistically significant in comparison with the control group. Also an increase in the absolute number of T lymphocytes (E-rosettes) was observed. Generally speaking, the values of blast transformations after mitogen stimulations were smaller in patients suffering from chronic than in those suffering from acute glomerulonephritis. In 1/3 of them, the decrease of blast response to one of the three mitogens was detected. The decrease exceeded the lower limit of values of healthy subjects, and most often, it was connected with Con A stimulation.

Blastic transformation of peripheral blood lymphocytes following stimulation with phytohemagglutinin during immunosuppressive therapy (prednisone 2 mg/kg body weight, indomethacin 2--3-5 mg/kg, azathioprine 2--4 mg/kg, cyclophosphamide 1-5--3 mg/kg per day) was studied in 59 patients with various morpholigic forms of chronic glomerulonephritis and in 7 with lupus erythematosus nephritis. No uniformly regular influence of immunosuppressive therapy in the doses employed in glomerulonephritis on blastic transformation in in vitro cultures was noted. The specific drug administered was not decisive for the character of the change in reactivity of lymphocytes (increase or decrease in blastic transformation). The interesting observation was made that efficacy of treatment was high in patients with lowest initial values of blastic transformation and its greatest increase during therapy. Apparently, disorders of cellular immunity assessed on the basis of blastic transformation of lymphocytes stimulated with phytohemagglutinin are not a decisive prognostic factor in glomerulonephritis. The results are discussed from the aspect of a possible influence of immunosuppressive therapy on restoration of the physiological proportion of T and B lymphocytes in peripheral blood.