This study was intended to clarify the indications for hemofiltration (HF) and simultaneous hemodialysis and hemofiltration (HDF) therapy which clears the uremic blood with the filtration process similar with the natural glomerular filtration, in patients with end-stage renal failure. 3640 treatments of HF and HDF were performed in total 60 patients including 45 males and 15 females with mean age of 44.1. The results were compared with those of conventional hemodialysis (HD) in the same patients to fulfill statistical requirement for evaluation. In HF and HDF, the incidence of disequilibrium syndromes and hypotensive attacks which needed some kinds of medical attention during the treatment decreased from 20 to 65% of HD. Fluid removal by HF and HDF was significantly superior to HD in safety and efficacy. From these results stated above which were confirmed with statistical reliability, we conclude that HF and HDF are useful and effective treatment methods for those patients who develop severe overhydration, hypo-tensive episodes and symptoms of disequilibrium syndrome resistant to conventional HD. Since these abnormalities differ in their etiologies, if we dare to categorize them into one clinical entity as an indication for HF and HDF, the term "dysdialysis syndrome" would properly be applied. In addition, it was noted that some patients were actually better on HF and HDF than HD in treatment of severe hypertension, uremic neuropathy, pigmentation and hypertriglyceridemia, although statistical superiority could not have been established for the lack in symptom-relatedd population. HDF shortened the treatment time from mean 5.64 hours of HD to mean 5.09 hours. In conclusion, HF and HDF are absolutely superior treatment forms to conventional HD in elimi-nation of " dysdialysis syndrome" with the definition and categorization stated above.

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The changes in serum concentrations of IgG, IgA, IgM and lymphocytes with time were assessed in 16 lipoid nephrotics given pulse therapy and 23 lipoid nephrotics treated with initial continued and alternate day oral prednisolone therapy. Consequent on pulse therapy serum IgG level was found to lower significantly to 40% of the normal value over a period from 2nd to 5th week. IgM attained to 100% 8 weeks after the initiation of pulse therapy, whereas it was kept as high as 160% even during the 10th week while on prednisolone. Serum IgA level decreased from 130% to 100%, but there was seen no significant difference between the two groups. The absolute number of lymphocyte increased during a period from 2nd to 4th week of treatment, but less markedly in pulse therapy group. FcIgG recptor cell fell in number following completion of the two therapy with no evidence of significant change in T- and B-cell ratio. On examination of adrenal reserve capacity according to rapid ACTH tolerance test 3 patients out of 16 were found abnormal. These observations suggest that pulse therapy may be thought to have a catabolism enhancing effect as well as an immunosuppressive action.

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Peripheral neuropathy and myopathy in chronic renal failure (CRF) were studied with special reference to their electrophysiological findings and also to the effects of dialysis. Of 57 patients with CRF, clinical neuropathy was recognized in 22 (33%), and reduced motor nerve conduction velocity (MCV) in 47 (70%). Clinical myopathy was observed in 13 (32%), myo-pathic changes on electromyography in 10 (24%) and elevated serum creatine phosphokinase (CPK) activity in 16 (39%) out of 41 patients with CRF. Thus the incidence of subclinical neuropathy was much higher than that of subclinical myopathy. Muscle weakness in CRF was proven to be due to either neuropathy or myopathy, or due to both in a few cases by electrophysiological and pathological studies. Positive relationship was not observed between the severity of slowed MCV in the peroneal nerve and serum concentrations of urea and creatinine. In contrast, serum CPK values were inversely correlated with serum concentrations of 25-hydroxycholecalciferol and calcium, which suggest thatt the abnormality of vitamin D metabolism may play an important role in the development of myopa-thy in patients with CRF. Short and infrequent hemodialysis performed twice a week, 4 hours for each time by using aa polyacrylonitril membrane (RP6) without the use of a closed recirculating dialyzate delivery system were effective in improving MCV in the peroneal nerve, and these observations suggest that the unknown middle molecular substances might be a possible pathogenetic factor of neuropathy in pa-tients with CRF.

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Fibronectin, a recently characterized high molecular weight glycoprotein being present in association with the surface of cells in connective tissues, was tested by immunofluorescence te-chniques for its localization and distribution in the kidney glomeruli obtained by biopsy. The biopsy specimens were classified according to the appearance of glomeruli under the light microscopy; minimal change lesion (Min), mesangioproliferative (P), membranous (M), membrano-proliferative (MP), and diffuse hyalinized (H), types. The distribution pattern of fibronectin in Min was similar to that of normal glomeruli in which only mesangium was stained by immuno-fluorescence. In P, the fluorescence was restricted to the mesangium but more prominent than in Min. When glomerular basement membrane (GBM), was involved as in M and MP, the fluorescence was found as linear pattern in close association with GBM. No fluorescence was detected in H, suggesting the requisite of functioning mesangial cells for the presence of fibronectin. The fluorescence was prominently found in crescent bodies, indicating that fibronectin is one of its componenents. The precise anatomical relationship with GBM of fibronectin present as a linear pattern and its pathophysiological significance have not been eluci-dated but should be interesting subjects in future studies.

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Dialysis without heparin was successfully performed with use of synthetic proteinase inhibitor, gabexate mesilate (GM). Although kaolin activated clotting time (KCT) in the dialyzer was pro-longed significantly, KCT of systemic blood was always normal because of good dialyzability and rapid inactivation of GM. Platelet count in GM group was significantly decreased, but its degree was not significantly different from that of dialysis with heparin (heparin group). Fibrinogen was not changed significantly in both groups. Other coagulation factors tested in GM group were not changed by dialysis. Effects of heparin on serum lipids during dialysis were observed in comparison with dialysis with GM. Totol cholesterol and phospholipids were not changed in both groups. In heparin group, triglyceride (TG) was decreased from 133±58(SD) mg/dl to 82±43 mg/dl(p<0.001), and free fatty acids (FFA) increased from 260±160 μEq/L to 620200 μEq/L (p<0.001) . The analysis of electro-phoretic pattern of lipoprotein revealed that, in heparin group, pre β and β lipoprotein of predialysis serum were fused into a new peak in postdialysis sample. On the other hand, in GM group, no changes were observed in TG, FFA and lipoprotein elec-trophoretic pattern. Since the dialysate contained 37 mEp/L of acetate and 200 mg/dl of glucose in both group, these data indicate that changes in lipids during dialysis can mainly be attributed to heparin which induces lipolytic activity from liver or other tissue, and that neither acetate nor glucose had any effect on lipids. Since high level of FFA might be contributory to dialysis-induced arrhythmias, heparin doses in dialysis should be reduced as low as possible. Dialysis with GM would show a favorable effect in such case. Thus, GM is established as a new member of anticoagulants for dialysis, or as an alternative agent for heparin in some group of patients.

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Angiotensin II (All) (0.075 ng/kg) was infused in 10 normal subjects during 20 seconds. Changes in left ventricular systolic time intervals (LVSTI) measured by mechanocardiography were examined. The LVSTI were QII, left ventricular ejection time and pre-ejection period. Their values were corrected for the heart rate (HR) and abbreviated to QIIc, ETc and PEPc. By response to the infusion of [1-Sar, S-Ileu] All (AIIA) (600 ng/kg/min) during 30 minutes, 10 normal subjects and 26 essential hypertensive patients (EHP) were classified into responder groups (RG) whose diastolic blood pressure (DBP) decreased more than 10 mmHg and others except for RG (non-responder groups : N-RG). Changes in hemodynamics measured by impedance cardiography were examined. By types of plasma renin activity (PRA), 32EHP were classified into high renin- (HRG), normo-renin- (NRG) and low renin groups (LRG). 1) HR decreased, QIIc, PEPc and PEP/ET increased, and systolic blood pressure (SBP) and DBP elevated by All infusion in normal subjects. 2) LVSTI, SBP, stroke volume (SV) and cardiac out-put (CO) didn't change, but DBP and total peripheral resistance (TPR) increased by AIIA infusion in normal subjects. 3) PEPc and PEP, ET were shortened, CO and cardiac index (CI) increased, and TPR decreased by AIIA infusion in RG. QIIc, PEPc, PEP/ET, BP and TPR increased, CO and CI decreased by AIIA infusion in N-RG. 4) To compare the values of the RG and N-RG before AIIA infusion, ETc was shorter, PEPc was longer, PEP/ET and TPR were larger, SV, stroke index, CO and CI were smaller in RG. BP and HR were the same in both groups. These suggested that the increased left ventricular load due to elevation of TPR was already present in RG. 5) To compare the three groups, the HR and QIIc were same, but ETc was the lowest in LRG and the highest in HRG. PEPc and PEP/ET were the highest in HRG and the lowest in LRG. These indicated that the cardiac load increased remarkably in HRG compaed with that in NRG and LRG. 6) Significant correlation was present between PRA and PEP/ET. Accordingly in EHP, LVSTI is available to ascertain if hypertension depends on All or not.

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The consecutive renal biopsy specimens of 151 children cases were immunofluorescentically, mor-phologically and clinically examined. Especially attention was paid to the cases having glomerular IgA deposition, and the cli.nicopa thological outcomes among the cases showing different patterns of the IgA depositions were studied. Morphologically, the examined cases included 6 membranous nephropathy, 13 membranoproli ferative glomerulonephritis, 7 incomplete membranoproliferative glomerulonephritis, 1 diffuse ores centic glomerulonephritis, 29 proli.ferative glomerulonephritis, 94 minor glomerular abnormalities and. 1 End Stage Kidney cases. By immunofluorescence, the cases with positive glomerular deposition of IgA, IgG and IgM were found in 28, 24 and 26% of total examined cases respectively. These im munoglobulins were mainly found granularly either along the glomerular capillary, mesangially or mesangiocapillary. In another respect, IgA positive cases were found in 55% of morphological proli-ferative glomerulonephritis cases and also noted in relatively high percentages in other types of glomerulonephritis. Comparing the cases with mesangial pattern of IgA deposition in the glomeruli to those with mesangiocapillary pattern, the formers were classified to the clinicopathologically rather milder group than the latters. Furthermore, within IgA mesangial pattern group of 14 cases showing segmentall mesangial deposition of IgA were found in 43%, and all of them revealed morphologically only slightt alterations. However, the cases with global mesangial deposition of IgA represented morphologically rather progressive proliferative glomerulonephritis. On the other hand, IgA mesangiocapillary pat-tern group consisted of morphologically rather advanced change cases and they all showing globall intraglomeralar deposition of IgA. As a resul, it was noted that IgA deposition in the glomeruli were seemed to be very common among the glomerulonephritis of childhood. Within the cases having the different patterns of in traglomerular IgA deposition, although the most cases of IgA mesangial pattern group may be in-cluded simplified disease entity of IgA nephropathy.

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The purposes of the present study are to investigate thickening of the glomerular basement membrane (GBM) in glomerulonephritis, to compare the thickness of the GBM in the histological types of glomerulonephritis, and to clarify the relationship between the thickness of the GBM and immune deposition or proteinuria. Biopsy specimens were obtained from 46 patients, aged 4 to 60 yrs., who showed proteinuria and/or hematuria. In the present study, glomerulonephritis was divided by the classification of I. Kihara into the following histological types; minimal glomerular lesions (minimal change), diffus endoc'apillaryy proliferative glomerulonephritis (D. End. PGN), diffuse mesangial proliferative glome-rulonephritis (D. Mes. PGN), diffuse proliferative glomerulonephritis with crescents (D. PGN with Crs.), membranous glomerulonephritis (Memb. GN) and membranoproliferative glomerulonephritis (MPGN). Immunofluorescent and electron microscopical findings were also taken into consideration in the classification on some cases. Two cases showing no histological changes (no changes) were also investigated as controls in the present study. Measuring points were set at the interval of 1 pm on the GBM at the peripheral part of the capillary loop in the electron micrographs of the magni-fication of 6, 600 or 10, 000 times. The results were at follows : 1. The GBM revealed a significant thickening in all types of glomerulonephritis as compared with cases of no changes (2 cases, 167 measuring points, 0.299±0.087 pm). Except for the difference between D. PGN with Crs, and D. End. PGN, there was a significant statistical increase of the thick-ness of the GBM in the following order; minimal change (3 cases, 236 points, 0.328±0.105 tam), D. PGN with Crs. (3 cases, 275 points, 0.349±0.100 pm), D. End. PGN (3 cases, 336 points, 0.354±0.109 pm), D. Mes. PGN (22 cases, 1, 601 points, 0.401+0.131 pm), Memb. GN (10 cases, 921 points, 0.751 + 0.479 pm) and MPGN (5 cases, 400 points, 0927±0.781 pm). 2. As to Memb. GN, the thickness of the GBM increased in proportion to the frequency of the presence of deposition in the GBM. The same result was obtained, even though measurements were carried out only at the points without deposition. 3. The cases of D. Mes. PGN were divided into two groups according to the grade of protei-nuria ; one was the group showing proteinuria under 1 g of protein perr day, and another was the group showing pra oteinuria of 1 g or more per day. The thickness of the GBM was 0.335±0.113 pm in the former, and 0.475±0.119 pm in the latter. When the cases were divided by the grade of proteinuria without any relation to the histological type, the GBM was also found to be significantly thicker in the cases of proteinuria with 1 g or more per day than in the cases of proteinuria under 1 g per day.

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The purpose of the present study is to investigate the role of HBe antigen in the pathogenesis of membranous glomerulonephtitis (MGN) in Japanese children. Of 364 children who underwent renal biopsy from 1978 in our institutions, 10 (9 male, 1 female, ages 1 to 14 years) were found to be HBs antigen carriers, and one additional patient was found 2 years proir to this survey. These 11 patients comprise the present study. All of them exhibited some abnormality on a routine uri-nalysis at one time during the course. Serum HB associated antigens were studied in all. A routine light, fluorescent, and electron microscopic study was performed on 14 biopsied specimens from the 11 children. In addition, direct immunofluorescence for HBsAg, HBeAg and HBeAg was done in the majority of the specimens. The 14 specimens were divided into 2 groups depending upon clinical manifestations at the time of renal biopsy (Group A : 9 specimens from 9 children with nephrotic syndrome or heavy protei-nuria, Group B : 5 specimens from 4 children with minimal hematuria). All of the Group A speci-mens showed MGN stage II or III and the Group B showed either minimal changes or MGN stage H. in all of the 5 Group A specimens studied HBeAg immune complex was present along the glo-merular capillary wall, but not present in any of the 4 Group B specimens. However, HBsAg was demonstrable in only one of the 9 specimens tested. At the time of renal biopsy, circulating HBeAg was studied in 8 children (Group A : 4, Group B : 4). It is of interest that all of the 4 Group A and 2 of the 4 Group B children were found to have HBe antigenemia. The above data suggests there is a highly significant relationship between glomerular HBeAg immune complex and the development of MGN. We believe that most cases of HB associated ne-phropathy seen in the Japanese children are HBeAg mediated MGN.

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One hundred and eight dialyzed and 85 undialyzed patients in chronic renal failure were studied on their clinical aspects of calcium metabolism. Then, 48 dialyzed and 14 undialyzed patients were investigated on the effects of 1α-OH-D₃ treatment for six months. The results were as follows : 1. Half of undialyzed and dialyzed patients showed low level of serum total calcium. Half of undialyzed and two thirds of dialyzed patients showed low ionized calcium (whole blood). 2. Two fifths of undialyzed and half of dialyzed patients exhibited high AlPase. About 90% of patients showed high serum iPTH. There was positive correlation between iPTH and AlPase. 3. Bone survey by X-ray showed half of dialyzed patients had abnormal findings. 4. Intestinal calcium absorption in both undialyzed and dialyzed patients was markedly impaired, while mean daily intake in 40 dialyzed patients was only 323 mg. Net calcium transfer during dialysis was correlated negatively with difference between serum and dialysate calcium concentration. Cal-cium and phosphorus balance study in 2 undialyzed and 6 dialyzed patients revealed -116 mg/day (mean) of calcium and + 118 mg/day of phosphorus balance. 5. Significant increase in serum total calcium was observed in dialyzed patients received 1α-OH-D₃. The patients, administered 1α-OH-D₃ and Ca lactate, showed significant decrease in serum phosphorus and Ca x Pi, while marked elevation of tatal calcium was found. The group with low serum total calcium and high AlPase showed significant increase in serum total calcium and Ca × Pi in parallel with decrease in iPTH and AlPase after 1α-OH-D₃ treatment. 6. However, undialyzed patients received 1α-OH-D₃ showed biochemical improvement, they also exhibited elevation of serum creatinine. The changes of creatinine correlated positively with those of Ca × Pi. It is concluded that many patients showed biochemical, roentgenographic abnormalities in calcium metabolism which seemed to be partially related to negative calcium balance and little dietary intake, so that 1α-OH-D₃ with calcium supplements may be considerably beneficial in this respect.

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Twenty three female rabbits divided into three groups, and rabbits of each group were injected intramuscularly with dimethoxyphenylpenicillin (DMPPC) 500 mg/kg/day for 5 weeks (group 1), with cephaloridine (CER) 150 mg/kg/day for 5 weeks (group 2) and with DMPPC 150 mg/kg/day × 5/week for 24 weeks (including 7 week intermission) (group 3). Histopathological examination of the kidneys revealed interstitial fibrosis, interstitial cell infiltration, tubular epithelial degeneration and casts in tubules in all of the groups. The significance was confirmed by point volumetry that tubular com-ponents decreased and interstitial components increased. The blastogenesis of the lymphocytes from the rabbits of groups 1 and 3 was highly stimulated by autologous serum and DMPPC or with kidney specific antigen and DMPPC, while it was stimu-lated by autologous serum alone in group 2. The results on group 3 might support the hypothesis that DMPPC acted as a hapten and kidney specific antigen acted as carrier protein. Also the peak of blastogenesis with DMPPC and kidney specific antigen was paralleled with development of the histopathological changes in group 3. On the contrary blastogenesis of lymphocytes in group 2 was unremarkablly stimulated with CER and kidney specific antigen. Histopathological changes were very similar but there might be difference in their cell-mediated immunity as expressed by the blastogenesis.

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