Dynamic changes of T lymphocyte subsets and serum immunoglobulin (Ig) E levels were studied in focal glomerular sclerosis (FGS ; 8 cases) and minimal change nephrotic syndrome (MCNS : 11 cases), Twenty-two healthy volunteers were served as a control group. T lymphocyte subsets were identified by the indirect immunof luorescence technique using monoclonal antibodies; OKT 3 (T 3 ; peripheral T), OKT 4 (T 4 ; helper inducer) and OKT 8 (T 8 ; suppressor/cytotoxic). Serum IgE was measured by the radioimmuno-sorbent assay. All patients were treated with prednisolone in a daily dose of 40 mg or 60 mg for 4 to 8 weeks, follow by maintenance dose of 10 to 20 mg a day for at least 2 years. Patients with FGS were clinically separated into 2 groups, according to clinical status in the fourth month after initiation of the steroid therapy. In group I, 4 patients who were responded to the therapy, resulting in disappearance of proteinuria were included, and 4 patients in group II failed to response, remaining in nephrotic state or incomplete remission (urinary protein excretion > 1.0 g/day) through the initial 4 months. In the nephrotic phase of FGS and MCNS, serum IgE levels were markedly elevated, but there was no significant change of T lymphocyte subsets. After administration of steroid, T 3, T 4, and T4/T8 ratio were decreased, and serum IgE returned to the normal range in group I. However, in group II, T3, T4 and T4/T8 ratio were increased, and serum IgE was decreased but still remained in a higher level. MCNS showed decreases in T 3, T 4, T 4/T 8 ratio and serum IgE and increase in T 8 after steroid therapy as observed in group I of FGS. This study clarified that FGS could be separated into two groups based on the clinical response to steroid therapy, and each groups might have individual response pattern of T lymphocyte subsets, suggesting an important role of the response pattern to determine a prognosis in patients with FGS.

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Fifty one female Wister rats preimmunized with native BSA were received daily intravenous injections of native BSA or cationic BSA for 6 weeks to induce serum sickness. Two rats out of 8 immunized with native BSA showed mesangial deposition of rat IgG, C 3 and BSA by immunofluorescence (IF) and mesangial proliferalive glomerulonephritis by light microscopy (LM). Rats immunized with cationic BSA (pI 8.3-8.7) showed linear deposition of rat IgG without C 3 along the capillary wall and protenuria ( > 50 mg/dl) one week after starting of daily immunizations. The intensity of rat IgG deposition became strong and the deposition of rat IgG in granular fashion was replaced for linear along the capilary wall, concomitantly accompanying the granular deposition of rat C 3 . Also, large amount of proteinuria ( > 300mg/dl) was observed. The localization of BSA deposition was same as rat IgG, but the intensity was faint throughout the experimental period, No or mild prolif erative glomerular lesions were observed in rats immunized with cationic BSA by LM. These results suggested that the pathogenesis of immune complex (IC) deposition in rats induced by daily injection of cationized BSA is different from those of native BSA and "in situ" IC formation is favoured to induced the IC deposition along the capillary wall by daily immunization with cationic BSA. In the early stage, the fixation of cationic BSA followed by deposition of anti BSA antibody on the capillary wall resulted in the loss of anionic charge of a basement membrane. This is speculated to be one of the most important factors to induce proteinuria.

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Pathogenesis of focal glomerular sclerosis was examined in adriamycin (AD)-induce nephrotic rats. Experimental animals were divided into two groups. Group I was induced with a single intraperitoneal injection of 6 mg/kg BW of AD. This group was sacrificed 1 and 3 days and 1, 2, 3 and 4 weeks after dosage, Group II was given dosages (3 mg/kg BW) four times at one week intervals, and sacrificed at 4, 6, 8, 12 and 18 weeks after the last injection. Glomeruli of 3 days to 3 weeks in group I showed minimal alterations but those of 4 weeks of group I and all the animals of group II showed focal glomerular sclerosis (FGS). The basic findings common to groups I and II by electron microscopy were glomerular epim thelial alterations, which were characterized by the foot processes, detachment from GBM, the presence of numerous intracytoplasmic vesicles and filaments (microfilament) of 5-6 nm in diameter. From the observation by immunof luorescent microscopy we suggested that the filaments in the epithelial cells were of actin. These actin filaments showed an increase in amount and unusual distribution in the altered epithelial cells. We suggest that an increase or abnormal distribution of actin filaments may lead to a deformation of the epithelial cells and their detachment from the glomerular basement membrane (GBM). This GBM then rapidly wrinkles, providing one of the causative factors of segmental sclerosis.

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Deposits of IgA and secretory component (SC) in the renal glomeruli were studied on 12 cases of IgA nephropathy (Berger's disease) and 8 cases of Henoch-Schonlein purpura nephritis. They were observed immuno-cytochemically by the light and electron microsn copic levels with fluorescence-laveled antibodies and peroxidase-laveled antibodies respectively. SC were stained positively by immunoelectron microscopic method in all cases. SC was identified with a distribution similar to that of IgA in both diseases. Therefore, it was assumed that there is a close relation between the etiology and secretory IgA deposition in glomeruli.

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Methylguanidine is possibly to be an oxidative product of creatinine. In this study, we investigated the effects of some reagents which were related to oxidation in some different pH conditions. Nonbiological synthesis of methylguanidine from creatinine (100 mg dl) in Tris-HC1 buffer was stimulated in acidic pH. Glutathione (final concentration 2 mg/ml) inhibited the synthesis of methylguanidine completely in the pH range from 6.6 to 8.2 within 12 hours, α-tocopherol (1 mg/ml) also inhibited the synthesis of methylguanidine in acidic pH. Ascorbic acid (1 mg/ml) stimulated the synthesis of methylguanidine in the pH range from 6.6 to 8. 2, and the stimulatory effect became stronger in basic pH. Stimulation and inhibition of methylguanidine synthesis by these reagents were also observed in the biosynthesis of methylguanidine in isolated rat hepatocytes. These results suggested that some substances such as glutathione, α-tocopherol and ascorbic acid might affect the methylguanidine synthesis in vivo.

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We found unidentified factor (s) which catalyzes methylguanidine synthesis from crea tinine in rat liver homogenate. This activity was brought about by heating the liver homo genate at 60°C for 10 minuets, but disappeared by heating over 80°C. In addition, this activity was inhibited completely by the addition of unheated homogenate. These results suggested that there might be stimulatory and inhibitory factor (s) of methylguanidine synthesis in rat liver homogenate. This activity was also found in the homogenate of the kidney and lung after heat treat-ment. However, the muscle, red blood cell, serum and stool had no activity of methylguani-dine synthesis with or without heating at 60°C for 10 minuets. Glutathione (final concentration 2 mg/ml) inhibited this activity completely. α-tocopherol (5 mg/ml) and ascorbic acid (1 mg/ml) inhibited this activity partially. These results present a clue to clarify the mechanism of methylguanidine synthesis in vivo.

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This study aimed to clerify that creatinine is oxidised to MG by active oxygen using various generators and scavengers of active oxygen. Exactly, we used 3 mM hypoxanthine and 0.015 units/ml xanthine oxidase as a source of superoxide radical, 0.05% hydrogen peroxide solution as a source of hydrogen peroxide, and 10mM FeSO₄ and 0.05% hydrogen peroxide as a source of hydroxyl radical. 100mg/ml creatinine was added to 50mM Tris-HCl buffer (pH 7.4 at 37°C), and incubated with generators of active oxygen at 37°C. The rate of MG synthesis in the incubation mixture containing creatinine and superoxide radical generator was 0.140±0.028 pmol/ml/ 5 sec., and it was inhibited by the addition of 300 units/ml superoxide dismutase. The rate in the mixture containing creatinine and hydrogen peroxide was 0.700±0.125 pmol/ml/ 5 sec. While, MG synthesis in the mixture containing creatinine and hydroxyl radical generator was at the rate of 25686±2105 pmol/ml/ 5 sec., and it was similarly inhibited by the addition of 0.16% sorbitol, 0.30% lactulose or 0.04% ethanol. These results suggest that creatinine is oxidized to MG by various species of active oxygen. Especially the effect of hydroxyl radical is most powerful, so the amount of hydroxyl radical derived from physiological concentration of iron and hydrogen peroxide may explain the MG production in the uremics. In addition, MG may be not only a uremic toxin, but also an index of peroxidative state in uremia from another viev-point.

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Experiments were performed on rats with chronic or acute renal failure in order to investigate the alteration of guanidino compounds. The purpose of this paper is to gain the profiles of urea cycle metabolism in renal failure, because the guanidino compounds, as uremic toxins, would take an important part in elucidating the clinical features of uremia. Chronic renal failure was produced by the method of Platt and acute renal failure was produced by bilateral Iigation of the ureter in male roister rats. The concentration of guanidino compounds in the plasma, brain, liver, kidney, skeletal muscle and intestine were measured by JASCO G-520 guanidine autoanalyser. In the rats with chronic renal failure, the concentration of guanidinosuccinic acid(GSA), guanidinobutyric acid (GPA), guanidine (G) and methylguanidine (MG) were increased in almost every organs, while arginine (Arg.) remained unchanged. However, the concentration of all guanidino compounds were not changed in the brain. In the rats with acute renal failure, a decrease of guanidinoacetic acid (GAA) and an increase of GSA, G and MG were detected in each organs. Furthermore, there was a decrease of Arg, and an increase of G and MG in the brain.

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Biopsy specimens of 165 cases with IgA nephropathy were examined by electron microscopy and the correlation between electron microscopical findings and the other laboratory data were analysed to clarify the indices and mechanisms of progressive disease. Electron microscopical findings were divided into two groups, dense deposits and periferal capillary wall abnormalities. The variation and frequency of these findins were as follows; mesangial deposits (100%), subepithelial deposits (17.0%), subendothelial deposits (22.4%), intramembranous deposits (4.2%), attenuation (66.1%), splitting (36.4%), interruption and indentation (11.0%), mesangial interposition (4.8%), spherical microparticle (11.0%) The cases with attenuation, splittig, and capillary loop deposits had decreased creatinine clearance compared with those without such findings. Under the investigation of the anionic sites of G. B, M. in 5 cases, reduced and disappeared polyethyleneimine stained particles were seen more frequently in the cases with decresed creatinine clearance than those with normal creatinine clearance. In conclusion, it was suggested that the capillary loop abnormalities as well as mesangial proliferation and sclerosis had an important role in progressive mechanisms.

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To elucidate intracellular magnesium content of patients with renal disease and on regular hemodialysis treatment, erythrocyte and mononuclear cell magnesium contents were measured. 31 patients with mild chronic glomerulonephritis (Ccr ≥ 30 ml/min), 15 patients with severe chronic glomerulonephritis (Ccr < 30 ml/min), 31 patients on regular hemodialysis treatment and 14 healthy subjects were included in this study. The content of mononuclear cell magnesium was significantly higher than the erythrocyte magnesium content. Mononuclear cell magnesium content was significantly higher in patients with severe chronic glomerulonephritis and on regular hemodialysis treatment than in healthy subjects. An inverse correlation between creatinine clearance and mononucler cell magnesium content was found, Positive correlation between content of mononuclear cell magnesium and potassium in patients on reguar hemodialysis treatment was found. However, correlations of mononuclear cell magnesium content with plasma c-terminal parathyroid hormone level and hematocrit in patients on regular hemodialysis treatment were not found. After hemodialysis treatment, plasma magnesium concentration was decreased, but erythrocyte and mononuclear cell magnesium contents were not changed. These results suggested that the intracellular magnesium retention accompanied with renal dysfunction was remarkable in mononuclear cell than in erythrocyte. No change in erythrocyte and mononuclear cell magnesium contents after hemodialysis treatment indicated slow exchange between these intracellular stores and the entracellular fluid.

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Four female patients showed persistent hypocomplementemia (less than 70% of normal CH 50) without any findings of liver diseases or collagen diseases. CH 50 and complement components were measured on serial sera and kidney biopsy specimens were investigated immunohistologically. The age at the onset of the disease ranged from 13 years to 42 years. During the follow up period of about 8 months CH 50 and C 3 level showed persistent mild decrease, while the 'protein concentration of C 4, C 5 and C 9 were within normal range. None of them had C 3 NeF detected by Vallota's method. All cases showed mild mesangial proliferative GN without predominant mesaugial IgA deposition. The characteristic changes of the glomerular basement membrane observed in MPGN were never seen by electron microscopy, Glomerular deposition of C3 was observed in 3 cases but most of the cases didn't show the deposition of early complement profile, which was compatible with an alternative pathway activation but the deposition of immunoglobulin was rather fluctuating in case to case. Glomerular lesions are caused not only by direct action of chemical mediators released by complement activation but also by complement deficiency. The persistence of hypocomplementemic state may be related to glomerular injury, though the pathogenesis was unclear. It is difficult to make diff erantial diagnosis of mild hypocomplementemic renal diseass such as SLE, MPGN and post APGN etc. in their early stage but these 4 cases may belong to a separate entity.

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A 59 Year-old man was admitted to hospital because of oliguria and an attack of gout. During the past 16 years, he has suffered from recurrent attacks of gout. He never received any drugs except for colchicine and antiphlogistics. Apart from these attacks, he had not suffered from chronic infections and inflammatory diseases. The physical examination showed multiple tophi on extremities. Laboratory studies revealed a hemoglobin of 7.7 g/dl, hematocrit of 23.1 %, and a white blood count of 10, 300/ mm³. The serum uric acid was 9.9 mg/dl, blood urea nitrogen 119 mg/dl, serum creatinine 13.1 mg/dl, total serum protein 6.2 g/dl, and base excess -11 mEg/l. The erythrocyte sedimentation rate was 155 mm/hour. Therefore, hemodialysis was started 3 times a week, and antibiotics and human serum albumin were received. After 18 days, he was admitted to because of paralytic ileus and hypotension. After 6 days, he died from pulmonary edema. The autopsy showed multiple tophi on extremities and right auricle, gouty nephropathy of both kidneys, systemic amyloidosis including various organs with kidneys, hydrothoraces, and hypertrophy of heart. Amyloid protein of renal glomeruli was amyloid A protein. Finally, we diagnosed this case a secondary amyloidosis associated with polyarticular gout. So far as we know, there has been few reports in the world on the secondary amyloidosis due to gout. But, many other chronic inflammatory arthritis includind rheumatoid arthritis, juvenile rheumatoid arthritis, ankylosing spondilitis, and psoriatic arthritis, often occur systemic amyloidosis. We discussed about the possible combination of gout with systemic amylodosis.

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Buerger's diseae, predominantly in young and middle-aged male smokers, is a non-specific inflammation of small and medium-sized arteries with thrombus obliteration and without arteriosclerotic change. Renal biopsy specimens from two cases of Buerger's disease showed unexpectedly mild mesangial proliferatve GN and predominant IgA deposition in mesangium, morphologically identical to primary IgA nephropathy. One was a 36-year-old man, the other was a 47-yearr old man. Both smoked heavily. They had never been pointed out urine abnormalities o Proteinuria and microscopic hemam tuna were observed in both cases first at the almost same time when Buerger's disease appeared clinically. It is considered too hasty to decide promptly that these two diseases are mere complica-tionsm These cases suggest heterogeneity of IgA nephropathy.

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The patient with primay hyperoxaluria was a man, aged 27 years. His illness started with abdominal pain; hematuria and proteinuria in At that time his laboratory data including blood urea nitrogen and serum creatinine showed a uremic state. An x-ray film of the abdomen revealed bilateral nephrocalcinosis with renal stones. From this data hemodialysis treatment was started in After 19 months of hemodialysis, on, a kidney obtained from his moo ther, was transplanted into his right iliac fossa. Postoperative course had been extremely good for 53 months, however, after that he developed high fever and colic pain, laboratory investigations disclosed a recurrent uremic state. So he was transferred back to outpatient hemodialysis therapy. During the period of chronic renal failure, he had venous complications such as hematoma, urolithiasis, urinary tract infection and so on. Death, preceded by supervened pain after onset of hematoma of inguinal region, was due to gastrointestinal hemorrhage. Microscopically, oxalate crystals were observed to be deposited most commonly in tubules in his own kidney as well as the transplanted kidney. The problems of managing terminal uremia secondary to primary hyperoxaluria were discussed.

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