Human and bovine tubuli were isolated by the passage of renal cortices through a series of stainless steel sieves of varing pore sizes. Tubular basement membrane (TBM) was isolated from tubuli either by sonic disruption or detergents. Observation on ultrathin sections of the final pellets isolated by both methods confirmed that pure TBM was obtained. Using electron microscopy after negative staining, human and bovine TBM isolated and observed under different conditions were shown to be a fine meshwork composed of pores and strands. The average diameter of the pores varied among samples. The diameter of the pores was approximately 4-7 nm in human and 4-8 nm in bovine TBM. For ultrastructural study, sonication has the advantage that the basement membranes retained their native structure to a larger degree, whereas the molecular sieve of basement membranes was sometimes destroyed by the treatment with detergent.

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The studies dealing with focal glomerular sclerosis (FGS) of Wistar rat were divided into three groups: such as untouched group, saline group and unilateral nephrectomy group. Particularly we investigated the percentage of development of sclerotic glomeruli. distribution of glomerular lesion in different layers of renal cortex, and relationship between the degree of glomerular alteration and severity of proteinuria under the timely observation for three groups. Among each group, glomerular changes of segmental sclerosis and global sclerosis increased by aging. Development of FGS which showed more than 5% damaged glomeruli were seen among 27 cases out of 54 cases (50.0%). Concerning distribution of renal cortex, cases with predominance of inner cortex were seen in 33 cases out of 54 cases (61.1 %) and 19 cases out of 54 cases (35.2 %) showed a relation between development of FGS and severity of proteinuria. Pathogenesis of FGS was not be cleared yet but as aging, glomerular overload, and blood circulating factor are concerned for this. Rat FGS cases were observed to have a high percentage of complications of tubuloin terstitial lesions, therefore both morphological changes are considered to involutionally grow worse.

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The interrelation between renal function and histological changes in the renal cortex were studied on 83patients with IgA nephropathy. The mesangeal proliferation, adhesion with Bowman's capsule, crescent, Hyalino-sclerosis, tubular atrophy, interstitial cell infiltration and fibrosis were classified in 4 orders (0 to 3). Immunof luorescence intensity of IgA, IgG, IgM, C3, and fibrinogen were also graded in 5 orders (o to 4). Final serum creatinine concentrations (FSCR) of 55 cases after mean observation period of 1.6±1.9 years were remained below 1.3 mg/dl (group A), of 13 cases after 1.8±1.5 years were in the range from 1.4 mg/dl to 1.9 mg/dl (group B), and of 15 cases after 2.4±1.8 years exceed 2.0 mg/dl (group C). There were no significant differences among these observation periods. The striking significant difference between groups A and B was obtained in interstitial fibrosis and gromerular hyalinosclerosis and between groups B and C in hyalinosclerosis. On the other hand, there was no significant correlation between serum creatinine concentrations and fluorescence intensity or combinations of the immunopro-teins. It is concluded that (1) mesangeal proliferation, adhesion with Bowman's capsule and crescent formation do not play an active role in the process of exacerbation of IgA nephropathy, however, (2) both of gromerular hyalinosclerosis and tubulointerstitial injuries accelerate the disease to the level of FSCR in the range from 1.4 to 1.9 mg/dl, (3) more marked hyalinosclerosis than that of the group B cause an aggravation of the disease to the final goal of renal insufficiency (FSCR>2.0), and (4) fluorescence findings do not indicate the prognosis of the IgA nephropathy.

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By electron microscopy, 109 patients with IgA nephropathy were studied. Spherical microparticles (SMPs) were found in 64 patients. SMPs were frequently observed in subepithelial space of the peripheral capillary wall (position 1), in subepithelial space of the paramesangial area (position 2) and in the glomerular basement membrane (GBM) of the paramesangial area (position 3). Some SMPs were observed at a part of localized attenuation of GBM or disrupted GBM. When SMPs were obseved in association with localized attenuation of GBM, there was tendency that where the more SMPs accumulated, the more GBM was found to be attenuated. And the more SMPs were observed at the part of disrupted GBM. Therefore, it was suspected that one of the processes of disruption of GBM in IgA nephropathy might be associated with appearance of SMPs. There was tendency that SMPs in position 1 were more frequently observed in the cases of diffuse proliferative glomerulonephritis than those of other histology, and the patients with SMPs in position 1 had decreased GFR, compared with those without such findings. Therefore, it was suggested that the lesion with SMPs in position 1 might be associated with the progression of renal disease in IgA nephropathy. And there was tendency that the patients with SMPs in position 1 had obvious microscopic hematuria, compared with those without such findings. Hematuria in some patients with IgA nephropathy may develop from the gap of GBM associated with SMPs.

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Carbon black suspension (25% diluted solution of Pilot black ink), 150mg/kg of body wt, was injected into normal rabbits. Open renal biopsy and/or nephrectomy were performed at intervals from 1 hour to six weeks after injection. Transient thrombocy-topenia and proteinuria were observed. The specimens were studied by light and electron microscopy. The results were as follows. Many aggregated platelets and carbon particles appeared in the glomerular and the peritubular capillary lumina at 1 hour after injection, carbon particles were found in endothelial fenestrae and mesangial matrix by 24 hours. They were not present in mesangial matrix at four days. The mesangial cells contained large carbon-filled vacuoles with a single limiting membrane at 24 hours after injection. This relative concentration of carbon particles in mesangium continued until two weeks. The relative concentration in mesangium decrea-sed from four to six weeks after injection, however, the frequency of juxtaglomerular apparatus cotaining carbon particles increased simultanously. These carbon particles noticed within the vacuoles surrounded by a single limiting membrane in the cytoplasm of lacis cells. Carbon particles were also found in the interstitial cells, such as fibroblast and other mononuclear cells, in the renal cortex from four days to six weeks after injection. Carbon particles did not penetrate the basement membrane of the peritubular capi-llary. They were not observed in the glomerular basement membrane, epithelial cells and urinary spaces.

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In the present study, we determined erythrocyte 2, 3-diphosphoglycerate (2, 3-DPG), hemoglobin Al (HbAl), oxygen dissociation curve (ODC), erythrocyte defor-mability, erythrocyte osmotic fragility and blood viscosity, using washed erythrocytes for the purpose of investigating causative factors of tissue hypoxia in patients with renal failure. Erythrocyte 2, 3-D and HbAI levels in uremic subjects, regardless of hemodial-ysis, were higher than those in normal subjects. The ODC for erythrocytes showed a right shift in uremic patients before heodial-ysis treatment. However, the ODC in patients with renal failure showed a left shift after hemodialysis. A decreased erythrocyte deformability and an erythrocyte osmotic fragility shifted to the yperosotic side were observed in uremic patients. Moreover, blood viscosity in non-hemodialysis uremic subjects was high at the shear rate of 334sec-1 as compared with that in normal subjects. The above data suggest that these factors are important in developing tissue hypoxia in the treatment of hemodialysis of uremic patients.

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Thyrotropin releasing hormone (TRH) was administered iv to 6 normal subjects and 32 patients with chronic renal failure (9 undialysed patients below Ccr 5 ml/ruin, 13 dialysed patients within 1 year and 10 dialysed patients over 1 year). The basal plasma TSH levels were slightly elevated in chronic renal failure compared with normal controls. The basal T4 levels were subnormal in all patients and tended to fall progressively the longer the patients were on hemodialysis. The basal T3 levels were subnormal in undialysed patients and dialysed patients within 1 year. After the administration of TRH (200μg), the prolonged and blunted release of TSH was found in chronic renal failure and the Max. ΔTSH levels in the patients with chronic renal failure (undialysed patients 5.5±1.1, dialysed patients within 1 year 7.2±1.1 and dialysed patients over 1 year 6.2±1.6μU/ml) were significantly different from normal controls (13.0±2.4μU/ml) (P<0. 05). There were no significant differences among chronic renal failure. However, the pattern of TSH release after TRH admini-stration in the dialysed patients was similar to that found in normal controls. These results suggest that there may be pituitary dysfunction in chronic renal failure. And this disturbance can be recovered slightly but not perfectly by adequate hemodialysis. There were no correlation between Max. ΔTSH and small molecular substances (BUN, CRN and UA) in chronic renal failure. So, the abnormality of TSH secretion in chronic renal failure may be related to middle molecular substance.

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In order to clarify the role of plasma carnitine on the pathogenesis of ischemic heart disease in patients with chronic hemodialysis (CHD), the measurements of plasma carni-tine, serum triglyceride (TG), serum total cholesterol, serum HDL-cholesterol, hematocrit and cardiothoracic ratio (CTR) were performed in 21 normal subjects, 10 patients with chronic renal failure without dialysis (CRF) and 41 patients with CHD. Blood pressure, heart rate and electrocardiogram (EGG) before and after double Master's two-step exercise test were also measured in 88 patients with CHD. As compared to that in normal subjects, the plasma carnitine level was significantly higher in CRF and lower in CHD, of wich the plasma level was remarkably reduced immediately after hemodialysis. In CHD, plasma carnitine gradually decreased during 2 years of HD, and the low plasma level of carnitine continued thereafter. In CHD over 2 years of HD, significantly negative correlations was found between the value of plasma carnitine and serum TG or CTR. Patients with positive ischemic change of EGG by exercise test had significantly longer duration of HD and higher value of left ventricular voltage (Sv1+Rv5 or Rv6) in ECG (LVH) and of double product than those with negative ECG change. In principal component analysis, symmetrically inverse situation between ischemic ECG change after exercise and plasma carnitine was observed. In discriminant analysis, ischemic ECG change closely depended on duration of HD, LVH in ECG, and low level of plasma carnitine. These results suggest that sustained hypo-carnitinemia might be one of important risk factors of ischemic heart disease in the patients with CHD.

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The opinionaire survey was performed for the Symposium regarding the choice of the treatment for renal osteodystrophy at the 24th General Assembly of Japanese Society of Nephrology in October, 1981. Answers were contributed from 82 hospitals in almost every district of Japan. Number of patients was 7, 297. Medical treatment was adopted in 95.1% of hospitals and in 80% of patients. No medical treatment was performed in 14% of patients. Single therapy with either of 4 kinds of drugs (calcium compounds, aluminum hydroxide gel, vitamin D preparations or calcitonin) was chosen in 35% of patients. Aluminum hydroxide gel was preferred in 95.8%, vitamin D preparation in 81.0% of hospitals. la(OH)D3 was most frequently used among other vitamin D pre-parations. Daily dosage of la(OH)D3 ranged from 0.5 to 1.5 pg. Calcitonin was admin-istered at doses of 20 to 80 u.at the time of dialysis. As to combined treatment, the combination of aluminum hydroxide gel and vitamin D preparation was preferred in 97.3% of hospitals and 81.9% of patients. The combination of calcium and vitamin D prepara-tions was adopted in 27.0% of hospitals and 3.5% of patients and that of calcium pre-paration, aluminum hydroxide gel and vitamin D preparations in 9.5% of hospitals and 6.0% of patients. Partial parathyroidectomy was indicated when other treatments were ineffective in 51 hospitals.

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In the present study, prostaglandin(A+E) levels in urine and plasma were radioimmu-nologically measured in normotensives(NT) and essential hypertensives(EH). The results obtained were as follows. (1) There is neither significant sex difference in urinary PG(A+E) excretion (UPG(A+E)⋅V, ng/hr/m2) in NT and in EH with normal renal function, nor is there significant difference between the two groups in the combination of males with females. (2) UPG(A+E)⋅V in EH with renal dysfunction is significantly and markedly lower when compared with EH with normal renal function. (3) UPG(A+E)⋅V positively and significantly correlates with UNa⋅V, urinary Na/K ratio and urinary volume both in NT and in EH, except for UK⋅V. (4) In EH, in combination with the patient with renal dysfunction, UPG(A+E)⋅V correlates neither with mean arterial pressure (supine) nor with hypertensive severity indices classified in Three Departments of Internal Medicine, Tokyo University. (5) Plasma PG(A+E) level in EH is significantly lower than that in NT, and is likely to be influenced by blood pressure rather than by the grade of renal dys-function. From these results, it appears possible to draw conclusion that in EH, alterations in urinary and plasma PG(A+E) level mainly relate to the renal handling of sodium and to blood pressure, respectively, and PG(A+E) plays some roles in their pathophysiology.

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The first purpose of this study is to investigate the effects of hypertension progress and increasing age on responses of plasma renin activity(PRA)to three different stimuli, such as 1) head-up tilt, 2) administration of loop diuretics (bumetanide) and 3) low sodium diet + administration of bumetanide + ambulation in essential hypertensive patients (EHT). The second is to examine the responses of PRA, plasma aldosterone concentra-tion (PAC), urinary sodium excretion and urinary kallikrein excretion to sodium load (120mEq Na/525ml for 1 hour) in ETH. The study was performed in 57 normotensives (NT) and 130 EHT, who were clas-sified as stage I and stage II according to WHO stage classification. The groups studied were age-matched in three groups (young ; below 39 years old, middle; 40 to 59 years old, ; above 60 years old). The results obtained were as follows: 1) The responses of renin release to three different stimuli did not significantly differ in NT and EHT of stage I. However, EHT of stage II showed significan-tly lower responses of renin release to old, all three stimuli than EHT of stage I and NT. Both EHT and NT showed significantly lower responses with increasing age. 2) With progress of hypertension and increasing age, PRA responses to sodium load were reduced and urinary sodium excretion after sodium load increased significan-tly, but PAC responses to sodium load were not significantly differed. 3) Urinary kallikrein excretion significantly increased after sodium load in NT and EHT of stage I. But EHT of stage II showed significantly lower basal level and response than NT and EHT of stage I.4) Urinary sodium excretion and urinary kallikrein excretion to sodium load were not influenced by administration of indomethacin prior to the examination. These results suggest that the fluid volume expansion is advanced with not only progression of hypertension but also increasing age. Reduced renal kallikrein-kinin system in EHT of stage II may contribute to this volume expanded state.

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