Cellular immunities mediated by lymphocyte may play important roles in the pathogenesis of the onset and progression of primary nephrotic syndrome. We have reported the decreased % of T and T_γ cells and increased % of B cells in the nephrotic stage of primary glomerulonephritis (PGN) We attempted to elucidate the presence of the antibodies to T_γ cells, T non-γ cells and to B cells byusing microcytotoxicity test in primary nephrotic syndrome. Studied patients were 8 cases of membranoproliferative glomerulonephritis (MPGN), 8 cases of minimal change glomerulonephritis (MCGN), and 4 cases of membranous glomerulonephritis (MGN), These cases were diagnosed by L.M., IF., and F.M.., The following results were obtained.1) In the nephrotic stage, complement dependent anti-T_γ cell antibodies were detected regardless of various renal histopathologies.2) High titers of anti-T_γ cell antibodies were associated with loss of peripheral blood T_γ cells in the nephrotic stage.3) In the nephrotic stage, anti-T non-γ cell antibodies and anti-B cell antibodies were also detected, although the titers of antibodies were less than the titers of anti-T_γ cell antibodies.4) These antibodies were not detected or decreased in the remission stage. These results suggest that these antibodies, especially anti-T_γ cell antibodies may play important clues in the change of lymphocyte subsets of the nephrotic syndrome with PGN.

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The steroid effects on N. S. have been investigated clinico-pathologically. As the parameters of clinical course, the acute phase reactants (APRs) were picked out. The latters were α₁-Antitrypsin (α₁-AT), α₁-Acidglycoprotein (α₁AG), α₂-Macroglobulin (α2M) and Haptoglobin (Hp), respectively. The quantitation of plasma proteins were carried out by single radial immuno diffusion method. Urinary proteins were analized by SDS-polyacrylamide gel electrophoresis (SDS-PAG)e They were classified into 2-patterns-selective glomerular proteinuria (SGP) and unselective glomerular proteinuria (UGP). The results were as follows.(1) APRs were correlated to clinical course of N.S.(2) 46.1% of SGP and 11.1% of UGP showed complete remission by steroid therapy, while 30.7% of SGP and 33.3% of UGP did not.(3) The selectivity was improved by steroid therapy-SGP (61.5%), UGP (33.3%). The levels of plasma proteins in N.S. especially APRs were regulated by protein turnover follow-ing urine excretion and shieving effect of GDM as well. However, the extent of inflammatory lesions would consern with the plasma protein levels.

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It has been suggested that patients with lipoid nephrosis (LN) have an immunological disorder. Toassess this, we studied the IgG synthesis of peripheral blood lymphocytes (2 ×10⁶ cells) from 7 nor-mal individuals, 3 LN patients, and 3 lupus nephritis patients (SLE) after 7 days of culture in the presence or absence of pokeweed mitogen (PWM). Untreated LN patients with nephrotic syndrome had significantly decreased levels of IgG synthesis (P<0.05) in the presence of PWM as compared with normal individuals (1100±310 vs. 1840±440ng/ml). In contrast, the levels of spontaneous IgG synthesis were significantly (P<0.01) enhanced in SLE patients as compared with normal individuals (4270±740 vs. 1170± 330). The rates of in vitro IgG synthesis correlated with the serum IgG levels in LN and SLE patients These findings suggest the possible defect in the immunoglobulin production of lymphocytes in LN patients.

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We had administered urokinase (U.K.) to the patients of nephrotic syndrome (N.S.) for two weeks with a daily dosage of 60, 000 international units in 1979. In spite of two weeks administration of U.K., there had been no change in the urine protein contents and the renal function, but the fibrinogen and serum FDP levels had been improved. From the results of these observations, it was doubtful to us whether the amount of U.K, adminic stered would be proper or not, for fibrinolytic therapy of N.S.. Then we measured. U.K. Lysis Time by the thromboelastograph (TEG) in order to determine the most suitable amount of U.K, for fibrinolytic therapy of N.S.. The results were as follows ;1) The K of TEG became shorter and the ma of TEG became larger in the case of patients of N.S. and renal failure compared with normal.2) When 70u/ml or 100u/ml of U.K. was added to the plasma in vitro, in each case, larger ma of TEG in N.S. was observed compared with in normal.3) The U.K. Lysis Time in the case of the patients of N.S. was prolonged compared with in the case of renal failure and normal people.4) When 100u/ml U.K. was added to the plasma in vitro, any change of fibrinolytis in TEG was not observed among several patients of N.S..5) When U.K. was added to the plasma in vitro, the dissociation between antigen and activity, wasobserved, as to the reduction of α₂-plasmin inhibitor.6) When 100u/ml of U.K. was added to the plasma in vitro, reduction percentage of α2-plasmin inhibitor activity was 45% in the case of N.S. and was 5% in normal.7) These observations suggest that the amount of U.K. with daily dosage of 60, 000 units was not enough for fibrinolytic therapy for the patients of N.S..8) The U.K. Lysis Time by TEG seems to be a good marker of fibrinolytic therapy for the patients of N.S..

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Sera from patients with idiopathic nephrotic syndrome (INS) inhibited lymphocyte proliferative response induced with Con A (Con A response) and rosette formation with sheep erythrocytes (E). In this paper. we studied correlation between immunosuppressive activity of INS serum and its serum lipid levels or lipoproteins. The inhibition of Con A response was observed not only with INS sera but with hyperlipidemic sera from patients with other glomerulonepritis and familial hypercholesterolemia. The concentration of cholesterol and phospholipid of inhibitory sera was significantly higher than that of non-inhibitory sera and the inhibitory activity was related to the level of serum lipid. On the other hand, the inhibition of E-rosette formation was observed with INS sera but not with other hyperlipidemic sera. The inhibitory activity was not related to the level of serum lipid. Lipoprotein deficit INS sera did not have an inhibitory activity on Con A response and E-rosette formation. Therefore, it was suggested that serum lipoproteins of INS serum was one of immunosuptl pressive factors on T-cell function.

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To get a clue to the fibrinolytic therapy for the children with various renal diseases, a total of 9 children, including 3 patients with persistent glomerulonephritis (IgA nephropathy), 2 with chronic glomerulonephritis (CGN) and 4 with purpura nephritis (PN) were treated with urokinase (UK). All of them showed varying degree of fibrin/fibrinogen (Fb/Fg), factor VIII-related antigen. (VIII R : AG) and factor XIII subunit-A (XIII-A) and subunit-S (XIII-S) deposits in the glomeruli. Daily dosis of UK was 2, 000-2, 5001.U./kg, The clinical effects were evaluated, based on the improvement of creatinine-clearance or urinary protein before and after UK therapy, and these informations were compared to the histological findings of the glomeruli and the changes of fibrinolytic factors in the plasma or urine during UK therapy. UK therapy was effective for 3 cases with IgA nephropathy and 1 with PN, whose histological findings revealed focal-diffuse proliferation with crescents (30-40%) accompanied with intense deposits of fibrin, and the excretion of D-dimer fragments in to urine were found during UK therapy. Thus, in these cases, the depressicn of the secondary fibrinolysis may be a significant factors in the clinical progress and pathological changes. On the other hand, D-dimer fragments which seemingly originate from fibrin in the glomeruli, were excreted earlier than UK therapy in 4 cases for which UK therapy was not effective, 3 cases with PN and 1 with CGN. The level of D-dimer fragments remaind unchanged during UK therapy. Though α₂-plasmin inhibitor levels in the plasma clealy decreased during UK therapy, no obvious differences were not found between effective and non effective cases.

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In order to investigate abnormalities of serum lipoprotein (Lp) metabolism in renal disease, especially in non-dialyzed patients with renal disease, serum Lp polyacrylamide-gel (PAG) disc electrom phoreses were performed in three groups of renal disease; 28 non-azotemic patients with nephritic or nephrotic syndrome (GN group), 26 azotemic patients with chronic renal failure who were not yet on dialysis treatment (CRF group), and 37 uremic patients on long-term hemodialysis therapy (HD group) Controls were 9 healthy adults. Blcod urea nitrogen and serum creatinine levels were within normal range in both the controls and the GN group, 74.3±7.7 (mean ±SE) and 6.6 ±1.2mg/dl in the CRF group, and 71.7±3.2 and 11.9±0.4mg/dl in the HD group, respectively.1) The number of patients with the broad-midband pattern (BMP) was 28 cases (76%) of the HD group.2) Electrophoretic profiles similar to the BMP were detected in 18 cases (69%) of the CRF group.3) In the GN group, there were 5 patients (18%) with electrophoretic profiles resembling the BMP, including of some atypical electrophoretograms.4) Such electrophoretic profile as detected in non-azotemic and/or non-dialyzed patients was defined as broad-midband pattern' (BMP') in this study.5) On the other hand, normal electrophoretic profiles were observed in 55% of fhe GN group, in 19% of the CRF group, and in 24% of the HD group. These results suggest that serum Lp abnormalities including BMP' or BMP originate in early stagesof renal disease, and then primitive BMP' is transformed into typical BMP when aggravating renal function and as hemodialysis therapy would be introduced.

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We suppose that heparin, used in hemodialysis, may play an important role in the pathogenesis of dialysis ostepenia. We investigate the adverse effect of heparin with or without renal failure, using rats. Sixty-eight Wistar-strain male rats were divided into 6 groups according to various treatment. (namely, sham-operation and partial nephrectomy, and furthermore the difference of drug, saline, heparin-Na, heparin-Ca.) And they were injected intramuscularly with heparin 400iu daily for eight weeks. The results are as follows. 1) Heparin administration induced obvious adverse effects on bone, including, i) diminished bone density and thinning of bone cortex width on bone soft X-ray.ii) increased bone resorption on contact microradiography.iii) increased urinary hydroxyproline excretion.iv) decrease of various bone parameters, such as, wet weight, inorganic weight, Ca content, P content, Ca/hydroxyproline ratio, P/hydroxyproline ratio.2) Partial nephrectomy treatment induced bone change, but the degree wasn't so prominent that the adverse effect of heparin was exaggerated furthermore.3) No difference was observed on adverse effect of heparin between heparin-Na and heparin-Ca.To summarize these findings, heparin administration induced adverse effects on bone. And the bone change was consisted of loss of bone mass and bone mineralization defect.

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In 8 hyperrtensive patients (5 primary and 3 malignant), some diuretics might cause the elevap tion of plasma Renin Activity (PRA), loss of body weight and accelration of hypertension. On the contrary, after the cessation of these diuretic drugs, lowering of elevated PRA, weight gain and amelioration of hyrertension were recognized. From these results, it was concluded that these transient hypertension due to diuretics might resulted from negative sodium-water balance in the body which in turn, stimulated renin-angiotensin system. The administration of diuretics, therefore, must be careful, especially in patients having emaciation, high PRA and hypopatremia which may reflect the negative sodium-water balance in the bodyo

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During two year periods between 1979 and 1981, we have experienced 28 cases of acute renal failure (ARF) with various causes. Among them 7 cases were thought to be originated from myoglobinuric ARF due to rhabdomyolysis. The causes of rhabdomyolysis were burns in one case, crush injury in one case, marathon running in one case, hypoxygenation from acute adrenal insufficiency in 2 cases and drugs in 2 cases. The serum and/or urinary level of myoglobin (Mb) detected by radioimmunoassy were moderately or highly elevated at the initial phase of ARF in these 7 cases. Also, there were hematest positive dark urine and dehydration of various degrees. There were no constant tendency in the serum level of uric acid, calcium, potassium in our cases with myoglobinuric acute renal failure (Mb-ARF), althought these parameters were fairly abnormal in Mb-ARF in the previous reports. Five cases received hemodialysis and two cases were treated conservatively. Six cases recovered completely from ARF and one case due to haloperidol induced Mb-ARF died, although frequent hemodialysis were performed. It was concluded that (1) Mb-ARF might be a considerably common cause of ARF, (2) measure-ment of serum and/or urine Mb might be very sensitive diagnostic tool for the differentiation of etiology of ARF. (3) However, Mb-ARF must be carefully differentiated from the acute exacerbation of chronic renal failure (CRF), since in patients with CRF the serum level of Mb were considerably high due to the disturbance of urinary excretion of Mb, (4) The outcome of Mb-ARF was relatively good.

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