Clinical study on nine cases (4.7%) of myoglobin-induced acute renal failure (Mb-ARF) out of 191 ARF experienced in our institution during the past 10 years was carried out and following results were obtained. 1) Age distribuition of Mb-ARF cases ranged from 15 to 61 y/o, average 37 y/o and all males. Swelling, pain etc. of extremities occupied 89% of all the clinical symptoms. Causes of rhabdomyolysis were classified as four cases of traumatic, three cases of non-traumatic and two cases of combined. Average time course of ARF was 40 days. 2) Laboratory examination revealed tendency of erythrocytosis, increased hematocrit, leucocytosis and extraordinary high value of myogenic enzymes. Blood urea nitrogen, serum creatinin, uric acid, potassium and inorganic phosphorus also increased, whereas calcium decreased. Histologic findings of muscle biopsy demonstrated severe myolytic degeneration at two to three days after the onset of Mb-ARF. 3) Infection, liver dysfunction and dehydration were complicated frequently in the objective cases. Conservative therapy was carried out for five cases, blood purification for four. Eight cases showed excellent prognosis, while ore case died in 55 days due to multiorgan failure and intracranial hemorrhage. 4) Frequency of Mb-ARF in various kinds of ARF revealed 4.7 to 25% referred from worldwide literatures including actual cases. 5) New classification of Mb-ARF was proposed as follows: I. traumatic, II. nontraumatic, III. combined, and each subgroups. Reported cases of Mb-ARF in Japan were collected as follows: 24 cases of acute exertional rhabdomyolysis, 10 cases of nontraumatic and two cases of combined. 6) Subgroups of Mb-ARF related to actual cases, viz., acute exertional rhabdo-myolysis, drug induced rhabdomyolysis and alcoholic myopathy were discussed. Patho-physiology, treatment and prognosis of the disease were also reviewed.

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The twelve children with hydronephrosis have been followed for the mean period of 2 years and 8 months. Their lesions were detected by the fetal echography in 8 (group A) and also detected within 4 months after their birth in 4 (group B). In group A the lesions were bilateral in 5 and unilateral in 3 and were due to the obstruction at the ureteropelvic junction (UPJ) except for one baby with urethral obstruction who died at 5 days old, but he did not have the oligohydramnios. The nephrostomy tube was inserted in 2 patients with severe unilateral hydronephrosis, but the nephrestomy was performed at 5 months old due to the poor urinary output and the urinary tract infection in one and the nephrostomy has been successfully continued for about 2 years in one. The other 5 children have been followed conservatively and the spontaneous improvement of hydrone-phrosis was observed in 4 and the lesion was unchanged in one. Hydronephrosis was detected by the various reasons in group B and was due to the bilateral vesicoureteral obstruction in 2 and unilateral UPJ obstruction in 2. The ne-phrostomy tube was inserted in one with severe unilateral hydronehrosis due to the obstruction at the UPJ, but it was removed after 3 months when the passage of the con-trast medium was confirmed at the UPJ. Spontaneous improvement was also observed in the other 3 patients. Recently the increasing number of children with the congenital hydronephrosis have been detected during their intrauterine life by the fetal echography and also at their neonatal period. Severe congenital hydronephrosis due the obstruction of the urinary tract requires surgical treatments, but the spontaneous improvement of these lesions with con-servative treatments or the nephrostomy was observed in 9 of 12 patients in this study. These observations should be considered in the managements of the surgical correction of the congenital hydronephrosis due to the obstruction of the urinary tract.

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To study the mechanism of steroid action on the pathogenesis of nephrotic syndrome, the author examined lymphocyte subsets using monoclonal antibodies in 52 children with steroid responsive nephrotic syndrome in the nephrotic, responsive and remission stages. single-color staining showed a relatively high OKT4/OKT8 ratio in the nephrotic stage as compared with the normal level. However, as proteinuria disappeared with steroid therapy, the OKT4/OKT8 ratio was lowered mainly because of a decreased number of OKT4 cells. The ratio became normal in the remission stage. HLA_DR⁺ CD8⁺ cells, suppressor-inducer T cells and suppressor T cells were examined by two-color staining to assess the kinetics of functional lymphocyte subsets. In children who responded to steroids, suppressor-inducer T cells were found to increase in the nephrotic stage, while suppressor T cells decreased. Treatment with steroid therapy resulted in a decrease in the number of suppressor-inducer T cells and an increase in the number of suppressor T cells and HLA_DR⁺ CD8⁺ cells. The above results indicate that the lymphoyte subset abnormalities in nephrotic syndrome mainly occur in suppressor inducer T cells and suppressor T cells, suggesting their possible relation with the etiology of the disease. The mechanism of action of steroids was considered to involve an increase in the number of suppressor T cells and a decrease in the number of suppressor inducer T cells.

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The laboratory and pathological findings are reported for 1b patients wttn membra-nous nephropathy (MN) ; 10 with MN associated with hepatitis B virus infection (HBV-MN) and 5 with idiopathic MN. Most of the patients were found by chance hematuria and/or proteinuria, and four patients showed the nephrotic syndrome. There was no clear difference in sex and age between HBV-MN and idiopathic MN. All 15 patients were well responded with steroid treatment; one patient with idiopathic MN relapsed once. In two with HB-MN, serum transaminase were markedly elevated and returned to normal after the termination of the steroid treatment. None of the patient with HBV-MN showed seroconversion during the follow up. Immunoelectron microscopic studies were performed on the kidney biopsy specimens from 8 patients (6 with HBV-MN and 2 with idiopathic MN). In all the cases, IgG and C3 were stained within the subepithelial electron-dense deposits (EDD). Membrane attack complex (MAC), demonstrating the activation of the late complement components, were localized at the same loci in all the patients but one with HBV-MN. HBe antigen was detected within the subepithelial EDD in 5 of 6 patients with HBV-MN. These data suggest the important contribution of MAC and HBe antigen-antibody complex in the formation of subepitelial immune deposits in HBV-MN.

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Active and inactive renins in the brain were measured in postmortem patients. 1) Trypsin-activatable inactive renin was the highest in the pineal body, followed by the pituitary, striatum, hypothalamus, midbrain, cerebellum, cerebral cortex and medulla oblongata. 2) Active renin was the highest in the pineal body, followed by the pituitary, hypothalamus, cerebral cortex, midbrain, cerebellum, medulla oblongata and striatum. These results show widely but specifically localized renin in the brain. The observed high amount of active renin in the hypothalamus, which has been recognized as an important region for control of autonomic nervous system, may be linked to modulation of the system through locally generated angiotensin II.

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Studies were performed on a pathogenetic role of anti-FN antibody in human renal disease and in experimental mice immunized with human FN. For this purpose, the auther measured serum anti-FN auto-antibody by ELISA in the patients with primary glomerulonephritis, in comparison with the healthy controls and the patients with diabetic nephropathy. The serum level of anti-FN antibody did not change, after immune complex was eliminated by pre-incubating the sera with polyethyl-ene glycol, anti-C3 antibody and anti-Clq antibody. Anti-FN antibody was positive in 46.2% sera of the patients with mesangial proliferative glomerulonephritis, but negative in the sera of the healthy controls and in those of the patients with diabetic nephropathy. Anti-FN antibpdy level did not correlate with the level of plasma FN and with the degree of proteinuria and hematuria. The male BALB/c mice which were immunized with the human plasma FN emulsified in complete Freunds' adjuvant were sacrificed during weeks 22. The control mice were not immunized. Antibody to human plasma FN was detected in all sera of immunized mice. The examination of the kidneys by light and electronic microscopy revealed mesan-gial proliferative alternation in immunized mice. From these results, the auther concluded that anti-FN antibody was detected with high incidence in the sera of the patients with mesangial proliferative glomerulonephritis and had some role in the initiation and progression of mesangial proliferative glomerulo-nephritis.

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Elastase has been known as having elastin lytic action and also as a drug having control action of hyperlipidemia and atherosclerosis. To investigate the action of Elastase on Masugi nephritis, 5 mg (group E₅) or 1 mg (group E₁) of Elastase and PBS (group E₀) as a control were ip injected every day for eight weeks. The rats were unilatelally nephrectomized at 4th week and sacrificed at 8th week. The amount of proteinuria was E₀>E₁≅E₅. Severity of fibrin deposits in glomeruli was E₀>E₁>E₅. Severity of the renal histology was quantitatively evaluated using the enlarged photographs by computerized surface measurement and were E₀>E₁>E₅ in glome-rular sclerosis, cresent and cellular infiltration of tubulo-interstitial tissue. The widening of glomerular tuft and Bowman's capsule were E₀≅E₁≅E₅. These data suggested that Elastase had protective action in the progression of Masugi nephritis and might be useful for human kidney diseases.

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Vascular eicosanoids (prostaglandins and thromboxanes) system is involved in the development or regression of arteriosclerotic changes as well as the regulation of vascular wall contractility. Thiazide diuretics have been reported to exhibit an arteriosclerotic effect, which may cancel the beneficial effects due to the hypotensive action of the agents. To assess the role of vascular eicosanoids system in the effects of thiazide therapy, we examined alterations of the eicosanoids system in aortic walls of spontaneously hypertensive rats (SHR) which had been treated with trichlormethiazide (8 mg/kg/day) for 2 weeks. Thiazide treatment significantly decreased systolic blood pressure in SHR by 10%, which was associated with a significant reduction in vascular prostacyclin (PGI₂) genera-tion by 29%. Thiazide diuretic lowered the PGI₂ production in both the aortic walls and cultured vascular smooth muscle cells (VSMCs) of SHR. A similar inhibitory effect was observed with furosemide. In contrast, the PGI₂ generation was stimulated by a non-thiazide diuretic, indapamide. The thiazide diuretic significantly lowered PGI₂ synthase activity in VSMCs of SHR without affecting the activities of phospholipase A₂ and phos-pholipase C. Thus, these data indicate that vascular PGI₂ generation is impaired in a prolonged treatment with trichlormethiazide partly through its direct inhibitory actions on PGI₂ synthase. The lowered PGI₂ generation is possibly related to the unbeneficial effects of thiazide diuretics on the sclerotic changes in the vascular wall.

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Long-term CaCO₃ treatment was studied in chronic hemodialysis patients. Twenty-three patients, who had been administered Al(OH)₃ before the study, were treated with CaCO₃. When pre-dialysis serum Ca had elevated beyound 5.5 mEq/L, CaCO₃ was reduced and Al(OH)₃ was administered again. Eighteen months later, serum P was controlled, and pre-dialysis serum P was less than 6.5 mg/dl in 13 patients with CaCO₃ alone. ALP levels significantly decreased, and serum aluminum was remarkably lowered in the patients who had discontinued Al(OH)₃. In patients who resumed Al(OH)₃, ALP levels rose after the resumption. The changes in serum aluminum concentration 48 hours after the infusion of 2 gms of desferrioxamine were significantly lower in patients who had discontinued Al(OH)₃ than in patients who resumed it, whereas no differences were noted between the two groups in dialysis duration and total amount of administered Al(OH)₃. These data indicate that CaCO₃ is an effective P-binder, which not only stops the progression of silent osteopathy presumably caused by oral intake of Al(OH)₃, but also may ameliorate the bone changes. However, further efforts will be necessary to control serum Ca within normal range, since the long term use of CaCO₃ induced hypercalcemia in almost half of the patients.

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To investigate the pathophysiological role of renal kallikrein-kinin system in diabetes mellitus, this study, first compared the urinary excretion of active kallikrein in 20 age- and sex-matched control subjects with 50 patients with type II diabetes mellitus who were normotensive without nephropathy, and second, examined the relationship between the urinary excretion of kallikrein and the efficacy of antidiabetic treatment. Urinary kallikrein was measured by the esterase method using pro-phe-arg-naphtylester as the substrate. The urinary excretion of active kallikrein was not significantly different between the controls and the diabetic patients (6.7±0.9<S.E.> vs 5.0±0.6 NU/24h/m², ns). However, the urinary excretion of active kallikrein was significantly less in diabetic pati-ents with hemoglobin Alc (HbAlc) equal to or of greater than 7% (group P) than in those with HbAlc of less than 7% (group G) ; 3.7±0.5 in group P and 7.6±1.0 in group G (P<0.01). Although the urinary excretions of inactive kallikrein and total kallikrein were also reduced in group P as compared with group G, urinary active kallikrein to total kallikrein ratio was comparable in two groups. There was a significant negative correlation between the urinary excretion of active kallikrein and HbA1c in the whole diabetic patients (r=-0.39, P<0.01). The reduced urinary excretion of active kallikrein in group P was associated with an increase in the urinary excretion of N-acetyl-19-D-glucosaminidase. Blood pressure, the urinary excretion of sodium, plasma renin activity and plasma aldosterone concentration were not significantly different between group P and G. These results suggest that the reduced urinary excretion of kallikrein in diabetic patients is related to inadequate treatment and that some tubular organic damage induced by hyperglycemia underlies the impairment of production of renal kallikrein.

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Continuous ambulatory peritoneal dialysis (CAPD) is now accepted widely as effective dialytic method for chronic renal failure in Japan. The magnesium transfer during CAPD is yet obscure. In this work, we studied the factors affecting transperitoneal magnesium flux in forty seven patients. All patients (forty two men and five women) aged 25-67 years (average 47 years) were treated by CAPD for 0.2-5.4 years (average 2.2 years). They were not medicated vasodilater, steroid hormone or magnesium containing drug. They were medi-cated calcium carbonate as phosphate binder or calcium supplement and la-hydroxyvitamin D3(0.25-0.75 rig/day). Their serum level magnesium was 3.21±0.31 mg/dl (mean±SD) and serum albumin level was 3.94±0.44 g/dl (mean±SD). Total magnesium removal was 43.71±4.97 mg/bag (mean±SD) and net magnesium efflux was +5.01±0.72 mg/bag (mean±SD). Transperitoneal magnesium flux was a signi-ficant correlation between total drainaged volume (TDV) [P<0.01] and serum magnesium concentration level [P<0.01]. Effluent magnesium concentration showed no significant correlation to effluent albumin concentration. It was a significant positive correlation to effluent PH [P<0.05] and a significant positive correlation to effluent calcium concentrations (total calcium and ionized calcium). However, there was no correlation between total magnesium and total phosphorus concentration in the effluent. Our observations suggest following four points. Firstly, patients treated by CAPD had moderate hypermagnesemia. The transperitoneal magnesium efflux was insufficient. Secondly, factors affecting Mg-mass tranfer were TDV and serum magnesium level. It was suggested that the latter factor was more important than the former. Thirdly, a dialysate containing lower magnesium concentration could be made available to improve hypermagnesemia. Finally, it might be suggested that the diffusable magnesium fraction (ionized and complexed magnesium fraction) was important in regard to transperitoneal magnesium flux.

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The patient was a 50-year-old woman who had been suffering from Raynaud's pheno-menon and morning stiffness for four years. She complained of pain in the knee joints two years previously, and has been treated with gold and non-steroidal anti-inflammatory drugs. On, hematuria (2+) and proteinuria (1+) were first found in her urine sample. She was hospitalized for further evaluation on Physical examination revealed scleroderma of hands, forearms and face, and arthr-algia, but no arthral deformity. Crepitant rates was audible in the basilar lungs. Blood pressure was 130/80 mmHg. The results of laboratory evaluations were as follows: urin-ary protein 2 to 3 g/day, creatinine clearance 110 ml/min, erythrocyte sedimentation rate 60 mm/hr, white blood cells 7, 100/mm³, serum immunoglobulins normal level except for slight elevation of IgM, complements normal level, circulating immune complex negative. Although the rheumatoid factor, LE cells, anti-nuclear antibody (titer 512, specked pat-tern) and anti Scl-70 antibody were positive, other auto-antibodies including anti-dsDNA and anti-RNP antibody were negative. Findings of skin biopsy showed increased collagen fibers in dermis. Renal biopsy showed focal necrotizing glomerulonephritis with small crescents, but no evidence of arteritis was found in the obtained specimen. Diagnosis of progressive systemic sclerosis was made, based on scleroderma, positive Scl-70 and findings of skin biopsy. Administration of corticosteroid (Prednisolone 20 mg/ day) started immediately for nephropaty. In the second renal biopsy at April of 1987, the glomeruli showed only a cicatrical lesion. No aggravation was noted in the findings of urinalysis and renal functions. We concluded that the corticosteroid therapy in this case was successful.

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In renal tissues from 20 children with primary IgA nephropathy (IgAN), the localiza-tion of immunoglobulins (IgG, IgA and IgM) and complements (C3c and C3d) was studied by immunoelectron microscopy (IEM). Patients who showed intense IgA staining within the mesangial electron-dense deposits (EDD), or positive staining in both the mesangial and capillary EDD, had severe proteinuria, hematuria and histological changes. IgA staining in both the epithelial and endothelial cells may be a result of antigen or immune complex digestion. Not only IgA and IgG but IgM also appear to be immunological partici-pants in the onset of IgAN. The intensity of C3c staining may be associated with the acute phase of IgAN. It seems that the localization of C3d is an indicator of the immuno-logical reaction in situ. Inhomogeneous staining in the EDD might represent old deposits.

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