Whether or not IgA nephropathy could be defined as a disease entity was investigated clinicopatho logically in 62 patients with primary glomerular disease, excluding membranous nephropathy, mem-banoprol if erative glomerulonephritis and minimal-change nephrotic syndrome. The patients were divided into three groups; M (mesangium, 35 patients), M-C (mesangium plus capillary, 12 patients) and C (capillary, 15 patients) according to the site of immunoglobulins deposition in the glomerulus. IgA was predominantly detected in the glomerulus in 31 (89%, IgA nephropathy), 10 (83%) and 9 (60%) cases in group M, M-C and C, respectitively. Their clinicopathological features were as follows 1) Patients in group M presented the most diverse clinical and histopathological appearances from mild to advanced glomerulonephritis, but 10 cases (32%) with episodes of gross hematuria were suffered from milder glomerulonephritis than the other cases without the episodes. The episodes were elicited in only one case in each group M-C and C (frequency ; 10% and 11%, respectively).2) Proteinuria over 1 gr/day was less common (35%) in group M than in the other two groups, and, on the other hand, it was most common (89%) in group C.3) In light microscopic findings, PAS-positive paramesangial deposit was most frequently observed in group M (61%), with decreasing frequencies in gronp M-C and C (30% and 13%, respectively). On the other hand, regardless of the site of immunoglobulins deposition, patients with predominant IgA deposition were suffered from milder glomerulonephritis than those with predominant IgG or IgM deposition. These results suggest that the clinical and histopathological appearances in primary glomerular disease relate mainly to the deposition sites rather than the classes of immunoglobulins. Furthermore, as the pathogenetic role of IgA is not determined, it is difficult to define a clinicopathological entity of IgA nephropathy based on only the immunohistological finding of predominant IgA deposition in the mesangium. In this investigation, however, it was appointed that a follow up study of patients present ing both the predominant IgA deposition in the mesangium and gross hematuria should be done for along period.

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Purified Cox. B4 virus was inoculated into the abdominal cavity of mouse, and the trend of virus and antibody titer of virus and changes in kidney tissue were studied for 16 weeks after inoculation of virus. Viremia developed at the 1st- 3rd day and 12th day after inoculation. The antibody titer of virus showed a biphasic rise in response to viremia on these two occasions. Changes in the kidney tissue occurred subsequent to the second viremia, presen ing a picture of proliferative nephritis. With the 6th week after virus inoculation as the peak, these changes mostly recovered thereafter, but findings suggestive of the progressive nature were obtained with considerable electron dense mes-angial and subendothelial deposits observed partly. Judging from the trend of virus and virus antibody titer and findings of the fluorescent microscopy, these changes in the kidney tissue were considered to indicate the immune complex type of nephritis which was produced by deposition of the circulating immune complex of virus and anti-virus antibody in the mesangium and basement membrane. Almost simultaneously with the appearance of glomerular iesion, infiltration of small round cells consisted mainly of lymphocyte was observed arterioles of the kidney. This is taken as the finding suggestive of the mechanism by which viral interstitial nephritis is produced.

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We have studied serum levels of guanidinosuccinic acid (GSA) and methylguanidine (MG), giving special attention toward longitudinal changes in the course of renal failure in relation to acute symp-toms associated with uremia. Serum GSA and MG levels were measured by the chromatographic methods according to Grof et al, and Stein. & Micklus, respectively. Hemodialysis was initiated with conventional Cuprophan dialyser in either condition : BUN avove 80 mg/d1, creatinine above 8.0mg/dl or displaying acute symptoms associa-ted with uremia.(1) In the stable state of renal failure, serum GSA or MG changed paralell with BUN or creatinine, respectively. The ratio of GSA to BUN (GSA/BUN x 100) was usually between 0.5 and 0.6.(2) At the start of hemodialysis, however, 16 patients displaying acute symptoms, such as CNS distur-bance, slow wave in EEG, uremic lung, pericarditis and severe vomiting, showed marked increase in GSA Level disproportionally to the increase in BUN, while the other 10 asymptomatic patients showed a similar level of GSA and GSA BUN as in the stable state.(3) Fourteen of 16 patients with acute uremic symptoms showed GSA/BUN above 1.0% at the start of hemodialysis. On the other hand, all of 10 asymptomatic patients showed GSA/BUN below 1.0.(4) Four patients of the symptomatic group, whose acute uremic symptoms continued despite intensive hemodialysis therapy, died within one month after the start of hemodialysis. In three of these four pat-ients, GSA/BUN remained above 1.0/ throughout the course These results indicate that serum levels of GSAA in relation to BUN, especially, the ratio of. GSA to BUN, might be a promising parameter for the managenent as well as the diciding the time to start dialysis therapy of patients with renal failure.

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Glycosylated hemoglobin (HbAI), a normal minor component of hemoglobin A has been reported to be elevated in subjects with diabetes mellitus. As the results of markedly elevated HbAI levels in diabetic patients with the sequela of severe nephropathy and with ketoacidosis, HbAI suggests the importance of studying the metabolic conditions of patients with renal failure. The level of HbAI in non-hemodialysed uremics with acidosis were increased to levels higher than that of normal subjects. In invitro studies, it was observed that HbAI was synthesized in red blood cells fromm normal subjects incubated for several days in 30mM triethanolamine HC1 buffer with various pH. HbAI levels in red blood cells incubated in pH 7.00 were elevated compared to that of pH 7.45 and pH 7a 70. The elevation of HbAI in the blood of uremics might reflect uremic substances. However, in the present stLldy it is suggested that the formation of HbAI is influenced by the blood pH level.

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The metabolic disorders in the uremic erythrocytes were investigated in the aspect of Nicotinam-ide Adenine Dinucleotide metabolism and the following results were obtained.1) NAD content in the erythrocytes of uremic patients undergoing hemodialysis was higher than that of normal subjects.2) In vitro study revealed that NAD biosynthesis from nicotinic acid-7-14C had been accelerated in uremic human erythrocytes3) Increased NAD content was confirmed in the erythrocytes of the nephrectomized uremic mice, however no increment was observed on other organs.4) NAD biosynthesis from nicotinic acid was also accelerated in the erythrocytes of uremic mice.5) NAD biosynthesis from nicotinic acid.7-14C was accelerated in the erythrocytes of uremic mice6) In order to survey the accelerating factor, the effects of pH, inorganic phosphorus concentrationn and uremic toxin in the medium on NAD biosynthesis in human erythrocytes were examined, but the acceleration of the biosynthesis was not induced.7) The accelerating biosynthesis of NAD from nicotinic acid in the erythrocytes of uremic patients was reproduced in the patient's hemolysate, and the accelerating factor was detected in the uremic hemolysate.8) The substance to accelerate NAD biosynthesis in uremic erythrocytes was an intracorpuscular subs-tance with less than 10, 000 in molecular weight. This was stable against heat, acid, alkaline and not soluble in the Folch's solution, and not permeable through the erythrocyte membrane.9) The activity of the accelerating factor and high NAD content in the erythrocytes of uremic pa-tients was not corrected by usual hemodialysis.

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Antisera were prepared in rabbits to the purified soluble human and pig GBM antigen (Hs-GBM and Ps-GBM) by serial immunization. Antigenecity of the Hs-GBM and Ps-GBM was investigated by the double immunodiffusion method, the immunofluorescent technique, the passive hemagglutination test and the various absorbtion studies using the rabbit antisera, the prepared human and pig renall tubular basement membrane antigen(TBM), the immunized rabbits and normal renal sections of human, pig, rat, rabbit, dog, guinea pig and mouse. Also, altered antigenecity of GBM in renal biopsy speci-mens of human renal diseases were examined by the indirect immunofluorescence. Their clinical diag-nosis were acute glomerulonephritis in 6, chronic glomerulonephritis in 20, membranous nephropathy in. 12, chronic membranoproliferative glomerulonephritis in 4, IgA-IgG nephropathy in 8, anti-GBM anti-body type glomerulonephritis in 2, lipoid nephrosis in 11, diabetic nephropathy in 2 and amyloid kidney in 2(1) no cross-reactive antigenecity between follows ;*GBM and TBM . Bowman capsule in normal human, pig, rat, rabbit, dog, guinea pig and mouse.*GBM·TBM·Bowman capusle and lung·liver·spleen·skin in human and pig.(2) cross-reactive antigenecity between follows*TBM and Bowman capsule in normal human, pig, rat, rabbit, dog, guinea pig and mouse.*human GBM and the other examined animal's GBM.*human TBM·Bowman capsule and the other examined animal's TBM Bowman capsule.(3) Altered antigenecity of GBM in human renal diseases was seen as follows *local glomerulur tuft in membranous nephropathy.*membranoproliferative glomerulonephritis*severe mesangial proliferative area, fresh crescent and sclerosing glomerulus in chronic glomeru. lonephritis.*nodular sclerosis in diabetic nephropathy.*amyloid kidney.

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Plasma vitamin A level was estimated by Natelson's method on 101 specimens (77 cases) in renal failure under hemodialysis. In chronic renal failure due to chronic glomerulonephritis, vitamin A level was 316±186 IU/dl, and 45 specimens (53%) were hypervitaminosis A (exceeded 300 IU/dl) on the contrary in hydronephosis, polycystic kidney and acute renal failure, vitamin A level did not exceed normal value. There were no significant relationship between vitamin A and sex, age, hemodialysis period, daily urine volume, and laboratory data, such as serum urea N, creatinine, calcium, phospharous, alkaline phosphatase, GOT, GPT, total protein, total cholesterol, triglyceride, 13-lipoprotein, hematocrit and pruritus cutis, but vitamin A level decresed when uremic patients were well stabilised condition on hemodialysis and well nutrition, or after renal transplantation. As above stated reasons, plasma vitamin A level is seemed to be one parameter, wheather uremic patient is well condition or not.

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It has been suggested that cell mediated immune response is suppressed in uremic patients in view of the low skin test reactivity, prolonged homotransplants survival, or the reduced reactivity of the lymphocytes to the mitogens and the second antigens in vitro. We studied in this paper three types of cell mediated cytotoxicity on chronic haemodialysis patients (HD), i. e., spontaneous cell mediated cytotoxicity (SC), PHA induced cytotoxicity (PIC), and antibody dependent cell mediated cytotoxicity (ADCC). Many reserchers consider that effector cells are NK cells in SC, cytotoxic T lyphocytes in PIC, and K cells in ADC`C. In our investigation, lymphocytes from HD revealed significantly low cytotoxic activity in comparison with those from healthy controls in these three assay systems. NK cells are considered to play some part in tumor rejection, while Sutherland et all reported the increased incidence of malignancy in chronic renal failure. It is interesting NK cell activity decreased in HD. It is widely accepted that cytotoxic T cells are generated by the stimulation of specific antigens or mitogens. Cytotoxic T cells are related to some infections in vivo. The spread of infectious diseases in HD may be partly due to decreased cytotoxic T cell activity. Although the role of ADCC is not yet clarified in vivo, it is an attractive mechanism because it is located in the point of contact between humoral and cellular immunity. There also was significant relationship between months on HD and SC or PIC activity at first five months of HD. Inamoto et al. reported that skin test sensitivity was the lowest at first three months of HD. These facts suggest that cellular immune function may be suppressed most severely at first several months of HD.

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As an assistant measure to normalize nitrogen metabolism in chronic renal failure, we tried to consider oxystarch to be useful in the basic and clinical studies. The combination rate of oxystarch and urea nitrogen has increased following rise of pH. The combination rate of oxystarch and uric acid, urea nitrogen, and ammonium were respectively 14.4±e. 6%, 22.1±7.0%, and 53.6±2. 5%, at pH 1.0, and also respectively 21(7±3. 4%, 46.7±2. 1%, and 100±0% at pH 7.4.(n=5) The combination rate of oxystarch, amino acid of glycine and histidine was around 30%, but with other amino acid it was under 10%. With the acute toxicity test for oxystarch given mice, LD50 was over 6, 500mg/kg. With the chronic toxicity test there was no significant difference in the growth situation of mice in the oxystarch group comparing with the comparison group. In the bilateral ligated ureter rats the survival rate of the rats were significantly increased of to administ rotor of oxystarch. In the rats survived over 48 hours after ligating bilateral ureter, there was more significant de-crease in serum urea nitrogen and serum creatinine in the oxystarch given group comparing with the comparison and the Kayexalate given group. In N.P.R. rats there was a significant decrease in serum urea nitrogen; from 43±5 mg/dl before dosing of oxystarch to 25±5 mg/dl after doing of oxystarch. (n=6) Using each jejunum, ileum, and colon of normal rats, bilateral ligated ureter rats, and N.P.R. rats, we measured the net flux of uric acid, from serous membrane side to mucous membrane side, by ever-ted sac method. Then, the net flux increased significantly in all cases by dosing oxystarch. Then, we gaoe 5 patients of chronic renal failure not having dialysis treatment, and also 5 pa-tients having dialysis treatmet for long time oxystarch of 20-40g per day for 5 to 20 days. And we found there was 39.3-36.6% decrease in serum urea nitrogen, but no significant change in creatinine and uric acid. From the above test results we consider that oxystarch is very useful as an assistant measure to normalize nitrogen metabolism for of chronic renal failure.

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