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In attempt to avoid a detrimental synergism between CsA and renal ischemia in the immediate postoperative period, ALG (425 lymphocytotoxic units/kg) with small doses of CsA (6-8 mg/kg) and P were applied as the initial immunosuppressive therapy in 14 recipients of cadaveric kidneys. ALG was administered for 5 to 14 days and 2 days before withdrawing ALG, Aza (2 mg/kg) was introduced. Results of this protocol were compared with those of 19 pts treated with CsA (12 mg/kg) and P. All the pts were followed for at least 12 months. The duration of posttransplant anuria was significantly reduced in the ALG/CsA/P group (p < 0.02). The sCr concentration after 12 months of observation was significantly lower (p < 0.05), no alterations in urinalysis were detected, the number of hypertensive pts was decreased. The acute rejection rates were equivalent in both groups, however 3 of 4 rejections in ALG/CsA/P group were resistant to steroids and occurred in pts with shortened period of ALG administration. The one year patient and graft survival in the ALG/CsA/P and control groups were respectively: 78.5%, 71.4% and 89.4%, 78.9%. Severe infectious complications in the group treated with ALG/CsA/P occurred in pts who were subsequently treated with OKT3.

We investigated the activity of some enzymes of the transcriptive DNA system to assess lymphocyte metabolic potential in patients with proliferative glomerulopathies. This study included analysis of the activity of three classes DNA-dependent RNA polymerases, before and 6 months after immunosuppressive therapy (Azathioprine + Prednisone). The enzyme activity was measured in nuclear extracts of T and B lymphocytes by estimation of the uptake of 3/H/UTP in the presence of alpha-amanitine. The immunoblotting technique using anti-polymerase I antibodies and nuclear proteins separation with immobilized exogenous DNA were employed to assess a type of the increase of the DNA-dependent RNA polymerase activity in lymphocytes populations (enhancement of the synthesis or limited depolymerization and degradation of the active enzyme). We found that the RNA polymerizing activity was increased in both lymphocyte populations. In T lymphocytes the increase was caused by an enhanced activity of transcript DNA enzymes, secondary to increased gene expression. In B lymphocytes an increase in enzyme activity was rather due to large stability RNA-polymerases in these cells. DNA-dependent RNA polymerase I in T and B cells was not modified by immunosuppression, while reduction in enzymatic activity of the remaining RNA-polymerase classes in T lymphocytes depends on partial limitation of their gene expression. Our study indicates that profound and various lymphocyte metabolic changes occur in patients with proliferative glomerulonephritis resulting from modifications in a gene expression and initiation of DNA synthesis in these cells.

The effect of immunosuppressive and anti-inflammatory drugs on the T and B lymphocyte populations, as well as cellular hypersensitivity in relation to GBM antigens (measured by MIF activity) in 60 patients with different types of glomerulopathy has been tested. The results were compared with a control group of 47 untreated patients and 32 healthy subjects. The treatment was carried out using the following drugs: azathioprine, cyclophosphamide, prednisone, ibuprofen and indomethacin. In a sample of 14 patients receiving ibuprofen and in 7 receiving arathioprine, indomethacin and prednisone, the T and B lymphocyte kinetics as well as MIF activity were repeatedly tested before and during the treatment of 150 days. In the patients under this treatment, a decreased percentage of lymphocytes with receptors for a complement as well as, in some cases. MIF suppression was observed. A comparison of healthy subjects and untreated patients with a group of 39 subjects tested for T and B lymphocytes as well as MIF activity after several months of the above treatment was made. It was found that supportive therapy with azathioprine and prednisone led to a normalization of B lymphocytes (EA and EAC rosettes) and to a small increase of T lymphocytes number. On the other hand, treatment with indomethacin and ibuprofen led to an increased B lymphocyte count (EA and EAC rosettes). Cyclophosphamide given with azathioprine caused a decrease in the proportion of T lymphocytes and an increase in the number of null cells. In addition, it was found that immunosuppressive drugs as well as anti-inflammatory drugs, even when administered in supportive doses caused in some cases, the suppression of cellular immunity as measured by MIF activity.

143 patients were evaluated clinically on the basis of the renal biopsy. Three methods for detecting circulating immune complexes (CIC) were employed: complement consumption test, inhibition of erythrocyte antibody IgG-EA rosette forming test and optical density of 4% PEG precipitated sera. CIC were present in the sera of all patients with acute poststreptococcal glomerulonephritis (2 weeks after streptococcal infection of the throat). In a group of patients with chronic glomerulonephritis the highest values in positive results were observed in lupus nephritis, chronic proliferative glomerulonephritis and chronic submicroscopic glomerulonephritis. These results were compared with levels of total hemolytic complement, C3, C4 components and serum immunoglobulins (IgA, IgG, IgM).

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.

The function of polymorphonuclear neutrophils in two groups of patients with glomerulonephritis was investigated. Patients were divided according to renal efficiency. In the group of 37 patients with renal failure a decrease in chemotactic activity, phagocytal index and iodination activity of leukocytes was observed (as compared with the control group). Our data indicate that renal insufficiency has some influence on the activity of polymorphonuclear neutrophils.

The EACA, known for its antihemorrhagic potential, has also been demonstrated to mitigate physiopathologic reactions linked activation of serum proteolytic cascades. Herein, we present results of experiments exploring a possible modification of nephrotoxic serum nephritis (NSN) in rats by the EACA. A combined intraperitoneal and oral administration of EACA to Lewis rats with the NSN (1 g/kg/12 h and 1 g/kg/24 h, respectively), significantly reduced albuminuria (p less than 0.05 EACA-treated rats vs. rats obtaining vehicle alone, days 2-3), enhanced endogenous creatinine clearance (ECC) - (p less than 0.01 - day 3) and attenuated renal histopathologic changes (day 3 post induction). The EACA given to control healthy rats did not cause any notable changes in the above parameters. We conclude that the EACA considerably diminishes the intensity of acute nephritis induced in rats by a nephrotoxic heteroantiserum.