The glomeruli showing focal and segmental glomerular sclerotic lesions were studied by electron microscopy in 20 patients with glomerulonephritis (GN) (13 with IgA-GN, and 7 with MPGN), 3 with focal glomerular sclerosis, 4 with preeclamptic nephropathy, and 6 with diabetic nephropathy. In addition to the routine staining using lead and tannic acid, periodic acid methenamine-silver (PAM) staining method for ultra-thin section was applied. The sclerosing lesions in various glomerular deseases showed the following morphological features non-specifically. Mesangiolysis was indicated by edematous appearance of mesangial matrix, irregular widening of subendothelial space and loose connection between mesangial cells and GBM. It was considered to be one of the most important alterations that would initiate the segmental sclerosis in morphological aspect. An increase in mesangial matrix, with the formation of collagen fibers and fibrills in it, caused irreversible direct mesangial invasion. Circumferential mesangial interposition also lead to severe narrowing of the capillary lumina. The presence of platelet-aggregates and fibrin-like structures in the capillary lumina, suggested that intravascular coagulation could play a role in forming segmental glomerular sclerosis. Insudation deposits with multiple densities were initially formed in subendothelial space and paramesangial area, and then became large enough to separate mesangial cells from GBM and to protrude into capillary lumina with the progression of sclerosis. Many foam cells seen in the mesangial area were markedly swollen and compressed the adjoining structures, resulting in luminal reduction and structural disintegration of the glomerular segment. Ultrastructural characters of these foam cells suggested that they possibly came from either macrophages or mesangial cells. Some types of the epithelial detachment were thought to cause adhesions between tuft and capsule. PAM staining revealed the severe GBM injuries clearly in the sclerotic area. These GBM changes are seemed to be final key events in the sclerosing process by inducing extracapillary lesions. These ultrastructural findings that ultimately induce the capillary closure are considered to be essentially common in forming irreversible glomerular sclerosis.

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The relationship between the immunological characteristics of circulating immune complexes (CICS), the immunoglobulin (Ig) class of glomerular immune deposits and the degree of mesangial proliferation has not been studied in detail. Using enzyme-linked immunosorbent assays for Clq binding (Clq EIA) and anti-C₃ (a-C₃ EIA) and molecular analysis by sepharose column, sera from patients with IgA nephropathy (IgA GN, N=53), systemic lupus (SLE, n=41) and other renal diseases (n=65) were tested for the presence of CICS and their correlation with glomerular immunofluorescent and histological abnormalities. In IgA GN, 55% of pathents had CICS containing IgA, usually in association with IgG or IgM. The majority of CICS were medium-sized (approximately 500 KMW) but ranged from 150 K to 1000 K. The degree of mesangial proliferation correlated with the presence of IgG CICS or IgM CICS, but not IgA CICS. The Ig class of glomerular deposits correlated strongly with the Ig class of CICS. SLE patients had high levels of IgG CIC and IgA CIC, 76% showed more than one Ig class of CIC; CICS ranged in size from 150 K to 1000 K. Serial studied before and after treatment in 5 patients demonstrated a reduction in all size of CICs in all patiens; 3 of these showed the complete disappearance of large and small CICS. A high correlation between the Ig class of glomerular immune deposits and the Ig class of CICS. In conclusion. CICS may play a role in the pathogenesis of glomerular lesions seen in IgA nephropathy and SLE.

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The effect of a selective Thromboxane A₂ (TXA₂) synthetase inhibitor, OKY-046, on reducing proteinuria was evaluated in the nephrotic rats. Protein excretion, and the contents of creatinine and arachidonic acid metabolites (6-keto-Prostaglandin F_1α and Thromboxane B₂, a stable metabolite of TXA₂) in urine were measured, and the synthesis of above compounds were also measured by biochemical assays using isolated nephrotic rat's kidneys. The preparation of nephrotic rats and the effect of OKY-046 on nephrotic rats were done as follows: male Wister rats were administrated daily subcutaneous injections of Aminonucleoside (7 mg/kg/day for 5 days and 10 mg/kg/day for 10 days), the effect of OKY-046 was observed by oral administration at 50 mg/kg/day, twice a day. Oral administration of OKY-046 decreased protein excretion in urine at the early stage of the disease. But at the developed stage, OKY-046 had no significant effects. Whereas Thromboxane B₃ excretion in urine was significantly inhibited during the all stage. On biochemical assays using nephrotic rats in the presence of OKY-046, Thromboxane B₂ synthesis was significantly inhibited as observed in in vivo assays, and furthermore inhibition rate of Thromboxane B₂ in cortex was higher than that in medulla. We suggest that excessive synthesis of Thromboxane A₂ in the hidney causes subsequent proteinuria at the early stage, and OKY-046 is effective on decreasing protein excretion in urine, but at the developed phase it can't decrease proteinuria no longer, probably many chemical-mediated factors except for Thromboxane A₂ and/or destructive lesions of the kidney would take part in proteinuria.

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The mechanism of polyuria associated with paroxysmal supraventicular tachycardia (SVT) was investigated in 8 patients whose SVT was provoked artificially by esophageal pacing. SVT was sustained for 60 minutes. Blood and urine samples were collected every 30 minutes from one hour before provocation to one hour after termination of SVT. Urine volume increasd in all patients more than two fold (on average 2.5 fold) of the control volume. Urine osmolality decreased from 546±66 (S. E.)mOsm/kg at the control period to 197±32 mOsm/kg at the peak of urine volume. Urinary Na excretion increased significantly (p<0.01) about 1.5 fold for 30 minutes after termination of SVT. Urinary antidiuretic hormone (u-ADH) was suppressed to one third of control period during SVT (from 30±11 pg/min to 8±2 pg/min), then increased significantly (p<0.05) to 74±15 pg/min after termination. Although plasma ADH level did not change during SVT, it tended to increased after termination. Plasma concentration of atrial natriuretic polypeptide (p-ANP) increased to 5 fold on average at termination of SVT and maximally attained value was 400 pg/ml. Urinary prostaglandin E₂(u-PGE₂) excretion increased after termination of SVT and percent changes of u-PGE₂ had a positive correlation with those of urinary Na excretion (r=0.64, p<0.001, n=5). Positive correlation was also found between percent changes of u-PGE₂ excretion and those of u-ADH excretion (r=0.72, p<0.001, n=5). The findings suggest the following conclusions: 1) The polyuria during SVT period was attributed mainly to the inhibition of ADH secretion, 2) Natriuresis after SVT period was due to i) the increase of p-ANP and ii) the release of renal PGE₂ associated with the increased ADH secretion.

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The relationship of the urinary excretion of NAG (U-NAG) and the renal function (Ccr, CH₂O, FENa) was studied after various ischemic periods (30, 60, 90 and 120 min) in rabbits, to clarify the significance of U-NAG on the ischemic renal damage. (1) U-NAG showed the peak after 60 min of total renal arterial occlusion (TRAO) and gradually decreased, while the renal function gradually decreased in proportion to TRAO time. (2) The urinary excretion of γ-GTP (U-γ-GTP) remarkably increased more than U-NAG after 30 min. of TRAO. (3) Ccr markedly decreased to 17% of control and CH₂O almost drawed to zero after 120 min of TRAO. (4) Urinary flow rate significantly increased on the ischemic kidney after reflow on every other occlusion time except 120 min of TRAO, compaired with control or non ischemic kidney, but it was not related with the ischemic time. These results suggest that U-NAG reflects the extent of the ischemic renal damage by TRAO, and must be useful as the index to detect the ischemic renal damage within 60 min. of renal ischemia. However, if the ischemic time is prolonged, U-NAG does not run parallel with the renal function and ischemic time, so this index may offer false estimation. Therefore, U-NAG should be consecutively measured with the routine renal function tests, and be assessed on the base of the data. 30 min of renal ischemia may impair mainly the renal brush border membrane of proximal tubules. The acute renal failure may be caused by 120 min. of renal ischemia. Urinary flow rate is inadequate as the parameter to detect the ischemic renal damage.

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The nutritional assessment in hemodialyzed patients is a still important problem although remarkable development of hemodialysic technique has been achieved. To assess the nutritional status of these patients, we made this survey by the method with dietetic interviews and diaries, urea nitrogen appearance (UNA) study, anthropometry, evaluation of the degree in social rehabilitation, and the measurement of serum protein (alubumin, transferrin, cholinesterase, C₃). The results of UNA study showed a close relationship to dietetic diaries in spite of mass study, and raised both the objectivity and authenticity. Certain anthropometric measurements were abnormal in the greater part of patients in the following parameters such as % relative body weight, skinfold thickness and mid-arm muscular circumference. From the synthetic evaluation of these measurements, the most patients remaind still malnutritioned, and it was suggested that they might intake a lowenergy diet. Meanwhile, 1.2 g of protein per kilogram of body weight is a sufficient dose for prescription. The low phosphorus diet cannot recommended at present, because it may force low protein diet to patients.

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To elucidate the difference of glomerular hemodynamics and function between subcapsular cortex and juxtamedullary cortex, we investigated an aspect of branch of afferent arteriole at the vascular pole, the observation of intraglomerular capillary anastomoses, and the measurement of inside diameter on the afferent and efferent arterioles by the scanning electron microscope (SEM) using plastic model of the glomeruli. This material were obtained 4 autopsied kidneys without renal disease. By SEM, the ovale shaped impression (probable representing the endothelial cells) in afferent arterioles and longitudinal folds in the efferent arterioles were seen. The afferent arteriole after reaching the vascular pole of glomerulus, almostly divided into three or four branches, more than 60% of glomeruli in 4 cases. However the difference of number and shap of arteriolar branches between both layers were not significant. The anastomosis of glomerular capillaries were mostly observed T-shaped anastomosis in all cases. The results of the measurement of inside diameter of afferent and efferent arterioles, the afferent arterioles in the subcapsular glomeruli were larger than the efferent arterioles. Novertheless the inside diameter of the efferent arterioles in the juxtamedullary glomeruli were nearly equal or larger than the afferent arterioles, statistically (t-test). Furthermore, standard deviation of the numerical value of efferent arterioles inn the juxtamedullary glomeruli were seen with great variation. These results is similar to our experimental model of FGS in a previous paper and it was suggested the followings: In subcapsular cortex, individual glomeruli are approximately equal of glomerular hemodynamics and function, but in juxtamedullary cortex, these hemodynamics and function may be different in individually.

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During a 5-year period from April, 1982 to March, 1987, an infra-red spectroscopic analysis was performed on 1, 828 urinary calculi obtained from Kanazawa University Hospital and its affiliated hospitals. The chemical compositions of the calculi were studied in connection to clinical characteristics. Especially, the calculi consist of calcium oxalate and calcium phosphate were investigated by dividing them into two groups with less than or more than 10% content of calcium phosphate. The results obtained were as follows: 1) The ratio of the upper urinary tract calculi to the lower one was 7.01 to 1. 2) The ratio of male to female patients was 2.64 to 1. Uric acid calculi were found more frequently in males than in females (p<0.01). On the other hand, magnesium ammonium phosphate and calcium phosphate calculi were found less frequently in males than in females (p<0.01). 3) The mean ages of patients with uric acid, magnesium ammonium phosphate and calcium phosphate calculi were significantly higher than those of patients with calculi of the other compositions (p<0.01). 4) The presence of concomitant urinary tract infection was significantly higher in magnesium ammonium phosphate and calcium phosphate calculi than in the other calculi (p<0.01). 5) The incidence of multiple and/or recurrent calculi was significantly lower in calcium oxalate calculi than in the other calculi (p<0.01). The incidence of spontaneous discharge of calculi was significantly higher in calcium oxalate and lower in magnesium ammonium phosphate calculi than in the other calculi (p<0.01). 6) In 1982 and 1983, 224 stones out of 299 (74.9%) were removed by open surgery. However in 1986 at which time percutaneous nephrolithotomy (PNL) and transurethral ureterolithotomy (TUL) were introduced, out of 185 stones, 74 stones (40.0%) were removed by PNL and 48 stones (25.9%) by TUL. Open surgery accounted for only 12.4%.

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The selectivity patterns of proteinuria were determined in 12 renal transplanted patients. The selectivity patterns of proteinuria were defined as the slope of regression line relating the log of renal clearance of β2-microglobulin (β2-m), lysozyme (ly) and IgG, relative to that of transferrin(tr), to the log of their molecular weights. In patients who were transplanted within 3 months, renal excretion of tubular proteins, such as β2-m and ly were increased, suggesting the presence of the damage in tubular reabsorption. In patients at stable stage, the selectivity patterns of proteinuria resembled to that in normal subjects. At progressive stage, renal excretion of glomerular proteins, tr and IgG, and/or tubular proteins were increased. The increased excretion of glomerular proteins suggested recurrence or de novo type of glomerulonephritis. The presence of chronic renal rejection was suggested in patients with increased excretion of both glomerular and tubular proteins. The present results showed that the determination of selectivity pattern is a useful tool to evaluate the function of transplanted kidney and the treatment effects.

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Pre-eclamptic focal glomerular sclerosis, hitherto an undescribed complication of IgA nephropathy, was diagnosed in two patients. A 37-year-old female (case 1) was first found to have microscopic hematuria at age 10, and had mild proteinuria during four prior pregnancies. At 26 weeks in her fifth pregnancy urinary proteinuria was noted again in association with elevation of blood pressure to 158/90 mmHg, followed by development of a nephrotic syndrome at 34 weeks and by cesarean section at 35 weeks. Renal biopsy, carried out beyond 2 months after delivery, because of persistences of proteinuria of more than 2.0 g per day and high blood pressure, revealed swelling of glomerular endothelial cells and hyalinosis together with foam cells and focal glomerular sclerosis, which was already known as a type of pre-eclamptic glomerular lesions, as well as typical lesions of IgA nephropathy composed of mild mesangial proliferation and mesangial IgA and C3c deposits. A 28-year-old female (case 2), presented with intermittent proteinuria following upper respiratory tract infection, was histologically proven to have IgA nephropathy. At 34 weeks in her second pregnancy, she showed (_??_) proteinuria and hypertension of 140/100 mmHg. As (_??_) proteinuria persisted for more than one month after delivery, renal biopsy was carried out, revealing almost the same pathological findings as observed in case1. After delivery, proteinuria decreased to 0.8 g per day in case 1 and became negligible in case 2 ultimately and final determination of GFR was estimated as 92 and 104 ml/ min, respectively. These results suggest that worsening of renal symptoms observed in the two patients may be attributed to a complication of pre-eclamptic focal glomerular sclerosis rather than exacerbation of underlying IgA nephropathy. This is the first report, which described the pre-eclamptic focal glomerular sclerosis as a complication of IgA nephropathy.

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A case of repeated membranous nephropathy after cadaveric renal transplantation immunosuppressed with conventional and ciclosporin was presented. Immunofluorescent and electron microscope were essentially available to make a diagnosis of membranous nephropathy. It was impossible to define recurrent or de novo membranous nephropathy, because histologic diagnosis of original disease leading to end stage renal disease was not established. Laboratory examinations revealed nephrotic range proteinuria and deteriorated graft function in every clinical course. Consequently, the outcome of every graft was poor and graftectomy was required. Concomitant chronic rejection played more important role than membranous nephropathy as a cause of graft loss under conventional immunosuppression. Circulating immune complex was studied to clarify the pathogenesis of post-transplant membranous nephropathy. Circulating immune complex was not found evidently. The presence of renal tubular epithelial antigen that was corresponding with nephritogenic antigen of Heymann nephritis was estimated by indirect immunofluorescent microscope. No evident deposition of renal tubular epithelial antigen was shown on membranous nephropathy after renal transplantation. However, some kinds of antigen derived from graft with chronic rejection and renal injuries may play an important role in pathogenesis of post-transplant membranous nephropathy.

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A case of Korean hemorrhagic fever in a 52-year-old male is reported. He travelled in Korea from High fever, chills, malaise, anorexia, and diarrhoea appeared on followed by back pain and macrohematuria on After the fever subsided on september 1, he complained of dyspnea and showed severe azotemia. Hemodialysis was initiated, and after 4 hemodialyses, his renal function was improved. Anti-Hantaan virus titer increased 128-fold. Renal biopsy showed massive lymphocyte accumulation around small veins in the corticomedullary junction along with acute tubular necrosis. This histological finding may indicate affinity of Hantaan virus for the vascular endothelium.

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In order to clarify the bone metabolism of renal osteodystrophy in long-term hemodialysis, the relationship between histomorphometric findings of biopsied iliac crest bone specimens and serum concentration of PTH, vitamin D metabolites, alkaline phosphatase, Ca, P and vitamin A was studied in 42 patients on chronic hemodialysis. (1) The serum level of C-terminal PTH was significantly correlated with the number of osteoclasts, osteoblastic activity and bone formation rate. In the patients, in whom the serum level of 1, 25(OH)₂D₃ was relatively low, osteoid volume depended on osteoblastic activity. Fibrous tissue was demonstrated in most of the patients showing more than 5 ng/ml of C-terminal PTH. It was significantly correlated with serum C-terminal PTH. (2) The serum level of N-terminal PTH did not reflect a long-time effect of PTH to bone. Serum C-terminal PTH seemed to be a more useful maker of bone histology than serum N-terminal PTH. (3) Serum 1, 25(OH)₂D₃ was correlated with bone formation rate. It was suggested that lack of 1, 25(OH)₂D₃ seemed to be one of the pathogenetic factors of osteomalacia in chronic renal failure. (4) Serum 24, 25(OH)₂D₃ was participated in activation of osteoclast and osteoblast. In patients with markedly low serum level of 24, 25(OH)₂D₃, coupling of resorption with formation seemed to become very weak, so that impaired calcification increased osteoid tissue. (5) Serum alkaline phosphatase was correlated with the osteoblastic activity. (6) The mineralization of bone matrix seemed to delayed in hypocalcemic patients. (7) Serum P had a tendency to increase in patients with increased resorption. (8) In patient with relatively low or normal serum level of C-terminal PTH, hypervitaminosis A stimulated the activity of osteoclast and osteoblast. In patient with markedly high level of vitamin A, the shifting from resorption to formation was disturbed, so that resorption surface increased subsequently.

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A 28-year-old male with a 10-year history of asymptomatic proteinuria received renal biopsy because of recently developed nephrotic syndrome and of impairment of renal function. Laboratory examinations revealed urinary protein of 5-7 g/day, total protein of 5.4 g/dl and glomerular filtration rate of 49 ml/min. In urinary sediments, oval fat bodies and cholesterol crystals were observed. Light and immunofluorescence microscopies revealed moderate mesangial proliferation and mesangium-dominant IgA deposits in association with small crescent formation in glomeruli. In addition, in the tubular lumens, especially in the corticomedullary junction, spindle or needle-shaped cholesterol crystals were observed. By electron microscopy, small crystals were found in the tubular epithelial cells as well as in the tubular lumens. Some of the latter were large enough to compress the epithelial cells and tubular basement membrane and grew out into the interstitium to form granulomas by infiltration of mononuclear cells surrounding the crystals (cholesterol granuloma). Of 258 patients with a histologically proven primary or secondary nephrotic syndrome, similar cholesterol crystals were observed in 7 patients (2.7%), two with membranous nephropathy, two with membranoproliferative glomerulonephritis and 3 with IgA nephropathy. However, the crystals were not found in 82 patients with minimal change nephrotic syndrome, in which nephrotic syndrome does not generally persist for a long time. The granulomas were observed in the 3 patients (1.2%) with IgA nephropathy. Six of the 7 patients described above showed an elevation of serum cholesterol level at the time of renal biopsy or during the nephrotic phase before biopsy. These results suggest that both choresterol crystals and granulomas may be formed in a circumstance of hypercholesterolemia, increased permeability of glomerular capillary wall and persistence of nephrotic syndrome, and to our knowledge, this case report is the first description of a patient showing cholesterol crystals and granulomas in renal tubules and interstitium in the Japanese literature.

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