Many investigators have suggested the presence of some unknown toxic substances, which accumulated in uremic sera but not in normal sera. However, these substances have not been identified chemically, and their biological roles and serum levels in uremic patients have not been clarified. The present dtudy was undertaken to elucidate and identify unknown toxic substances in uremic sera by the methods of gel-filtration, ion-exchange chromatography, high voltage paper electrophoresis and amino acid analysis. The results obtained were summarized as follows. (1) The chromatographic pattern on Sephadex G-75 of uremic sera consistently showed three peaks (I, II and III) higher than those of normal sera. (2) Ion-exchange chromatography of Peak Iand the structure analysis of the major component of the Peak revealed the accumulation of. β₂-microglobulin in uremic serum. (3) Analysis of Peak II of uremic serum by high voltage paper electrophoresis demonstrated the presence of five unidentified ninhydrin-positive substances. These substances were identified as .β-aminoisobutyric acid, .β-aspartylglycine, N-monoacetylcystine, homocysteic acid and cysteic acid by comparison with authentic samples, respectively. (4) The quantitative determination of .A-aspartylglycine, N-monoacetylcystine and, .A-aminoisobutyric acid in plasma revealed that the plasma concentrations of these substances in uremic patients increased much higher than those in normal subjects. Many investigators have suggested the presence of some unknown toxic substances, which accumulated in uremic sera but not in normal sera. However, these substances have not been identified chemically, and their biological roles and serum levels in uremic patients have not been clarified. The present dtudy was undertaken to elucidate and identify unknown toxic substances in uremic sera by the methods of gel-filtration, ion-exchange chromatography, high voltage paper electrophoresis and amino acid analysis. The results obtained were summarized as follows. (1) The chromatographic pattern on Sephadex G-75 of uremic sera consistently showed three peaks (I, II and III) higher than those of normal sera. (2) Ion-exchange chromatography of Peak Iand the structure analysis of the major component of the Peak revealed the accumulation of. β₂-microglobulin in uremic serum. (3) Analysis of Peak II of uremic serum by high voltage paper electrophoresis demonstrated the presence of five unidentified ninhydrin-positive substances. These substances were identified as .β-aminoisobutyric acid, .β-aspartylglycine, N-monoacetylcystine, homocysteic acid and cysteic acid by comparison with authentic samples, respectively. (4) The quantitative determination of .A-aspartylglycine, N-monoacetylcystine and, .A-aminoisobutyric acid in plasma revealed that the plasma concentrations of these substances in uremic patients increased much higher than those in normal subjects.

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A survey has been made of 210 cases of acute renal failure. The overall mortality was 37.1 per cent. Of the patients, 128 were male and 82 female, ranging in age from 5 to 79 years. The clinical, biochemical and other data were compared statistically, and factors affecting the prognosis in these patients were evaluated prospectively. Some major factors have been identified as having an adverse influence on prognosis, namely age, sex, etiology of acute renal failure, maximal blood urea nitrogen, and complications. Mortality rate rose with age, being especially high in those patients over the age of sixty, and was twice as high for male as for female, probably due to the preponderance of females in the etiologic group with the lower mortality rate and maybe due to unknown factors. Mortality was high in post traumatic group and postsurgical group, especially gastrointestinal and brain surgery. Blood urea nitrogen. mortality rose with the daily rise of BUN, but was not statistically significant. Maximal level of BUN was high in the poor prognosis group. Complications: infections, especially septicemia and pneumonia, gastrointestinal hemorrhage, congestive heart failure, coma had an adverse influence on prognosis.

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A laboratory model of membranous glomerulonephritis was induced in rats by the injection of pronase-digested homologous renal tubular epithelial antigen, and the renal lesions in the experimentallyinduced nephritis were studied sequentially by electron microscope. Rat tubular antigen, which was obtained from pronase-treated tubular segments and partified by gel filtration through a Bio-Gel column, was emulsified in the same volume of Freund's adjuvant and injected in rear foot pads of rats. After the antigen injection, urinary protein was determined quantitatively and the kidneys were obtained by unilateral nephrectomy or sacrifice at the intervals of 1-4 weeks. Proteinuria developed about 6 weeks after the antigen injection. In the renal specimens taken 3 weeks after the antigen injection, a few electron-dense deposits were first detected along subepithelial surface of the GBM. Epithelial foot processes often fused to each other at the place of deposition. After the appearance of proteinuria, the amount of deposits increased in number and size, and the fusion of foot processes became widespread. Small deposits were also found near the epithelial slit membrane. In the more advanced cases, about 3 months after the appearance of proteinuria, the GBM was thickened irregularly, containing many deposits within it, In much more survived rats, the deposits were seen a rough granule. There were some areas of low electron density or electron-lucent areas. These ultrastructural changes observed in the experimental nephritis were similar to those observed in human membranous glomerulonephritis. In some rats, however, which were weakened gradually and dead within 6 months after the development of proteinuria, marked thickening of the GBM with numerous dense deposits were found. No electron-lucent areas in the GBM were observed in these rats.

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In 51 regular hemodialysis patients, the relationship between the degree of anemia and the nutritional status was investigated. Following conclusions were made ; 1) In patients without iron deficiency (serum iron>110γ/dl), the serum transferrin levels correlated well with the caloric and protein intake, and also with the degree of obesity. Thus the serum transf errin levels are regarded as an indicator of nutritional status. In these patients, the serum transferrin levels correlated significantly with the RBC and hemoglobin levels. And the correlation between dietary intake and hemoglobin levels was also significant. These findings suggest that if protein and calorie intake is inadequate in dialysis patients, anemia become more severe, probably due to decreased globin synthesis. 2) In patients with low serum iron levels (serum iron≤110γ/dl), there were no significant correlations between the degree of anemia and each of serum transf errin levels and dietary intake. This seems attributable to changes in serum transf errin levels, decreased red cell production or reduced hemoglobin synthesis probably caused by the presence of iron deficiency, insidious chronic inflammation, or RE-block. 3) From the viewpoint of nutrition and anemia, it is conceivable that caloric intake of 35-40 Cal/kg and protein intake of about 1.2 g/kg is adequate in patients on thrice weekly hemodialysis.

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Dspyrsdamole was used in 30 cases of nephrotic syndrome, mostly of intractable type. The results indicate that the drug therapy proved to be effective in decreasing urinary protein and controlling nephrotic condition in 40% each of cases after an initial period of treatment. Long-term results of the drug on urinary protein and on nephrotic condition were rated as good in 36.4% and 53.3% respectively, of cases treated. The exact mechanism of action of dipyridamole in the nephrotic syndrome is still obscure in many respects. However, the fact that the drug shares its anti-platelet action with the non-steroid anti-inflamat ory drugs, e.g. aspirin and indomethacine, and the rapidty with which it produces its urinary-proteinn decreasing effect strongly scggest that it acts to inhibit the release of vasoactive amines and other chemical mediators from blood platelet. So far as the present study is concerned, adverse side-effects of dipyridamole were few or minimal, even when the drug was used in large dose over a prolonged period of time. From these results it is considered that dipyridamole provides a new remedy which is worthy of trying in nephrotic syndrome as a means of reducing the requirement of steroids and immunosuppressive drugs.

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We report here 13 patients with idiopathic nephrotic syndrome examined by kidney biopsies at 5 months to 12 years intervals. All of the initial biopsy specimens showed 'minimal change'. At the second biopsy, however, 5 cases were diagnosed as focal glomerulosclerosis (FGS), because there observed sclerosing lesions with eosinophilic deposits, hyaline thrombi, foam cells and vacuoles in three or more glomeruli. Besides in these specimens interstitium was also more increased than in initial biopsy speci-mens. By retrospective detailed histological examination, 4 initial biopsy specimens from FGS patients showed segmental mesangial thickness and capsular adhesions to capillay loops in one or two glomeruli. Clinically, these 4 cases had been steroid-resistant from the early stage and more than 1g/day of urine protein remained throughout the follow up periods. One of the 4 FGS patients never showed throughout the follow up periods. One of the 4 FGS patients never showed any improvement in the nephrotic syndrome, and took a downhill course to uremia necessitating hemodialy sis 7 years after the onset of the disease. In another patient with FGS, steroid therapy was at first effective, but he died of renal failure 16 years after the onset. In the other 3 patients second biopsy specimens showed no abnormality but a few proliferative or hyalinized glomeruli. These cases were steroid-responsive and the renal function was not deterior ated throughout the follow up periods, although they often needed steroid therapy because of relapses of nephrosis. Four biopsy specimens from patients with FGS (3 at the second biopsy and 1 at the third biopsy) and 3 second biopsy specimens from patients with 'minimal change' were studied by immunofluorescent technique. Significant depositions of IgM and .β1c were demonstrated in all of FGS but no deposition in 'minimal change'. These findings lead us to assume that FGS is caused by different factors from that of 'minimal change' type nephrotic syndrome.

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Serum 25-hydroxyvitamin-D (25-OH-D) was determined in 24 normal subjects and in 60 patients with chronic renal failure (CRF). Mean concentration of 25-OH-D was low (25.4±11.2 ng/ml) in sera from the patients as compared with that (33.9±10.6 ng/ml) of normal controls, although the values in earlier stage of the renal failure were considered to be within normal ranges. In more progressive stage, however, the value decreased extremely (11.3±5.5 ng/ml)e In contrast, the patients receiving regular hem. odialysis 3 times a week showed an almost idetical serum 25-OH-D level (26.4±11.2 ng/ml) to those of another normal controls, the level of which had been measured in winter season. The protein intake by patients with CRF is limited depending upon the degree of disturcance of their renal function, although such a diet therapy was not given to the patients when their chronic hemodialysis was started. The reduction of serum 25-OH-D levels in patients with CRF would be thus attributed to the limitation of vitamin D intake resulting from diet therapy with low protein intake. The estimation of excretion of 25-OH-D in the urine was performed on the urinary samples from 5 normal subjects and these from 24 patients with renal diseases showing proteinuria. Mean urinary excretin of 25-OH-D in 5 control subjects was 4.8±4.7 ng/day whereas those of the patients with light (urinary protein<3.5 g/24h) and heavy (urinary protein>3.5g/24h) proteinuria were 24.3±19.9 ng/day and 75.5±43.9 ng/day respectively. By the administration of 25-OH-D (200 μg) to the same subjects, this tendency became more remarkable. Since concomitant 25-OH-D binding activity appeared in the urine, renal loss of low molecular weight protein (Transcalciferin ?) supposed to be the cause of low circulating serum 25-OH-D levels in heavy proteinnuric patients. The present data suggest that low levels of serm 25-OH-D in patients with CRF might be due to the leakage of 25-OH-D in the urine as well ar due to the diet therapy with low protein intake.

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