In order to clarify the cause of the decrease in the urinary excretion of NAG (U-NAG) in severe ischemic renal injury in rabbits, we studied intrarenal energy metabolism in ischemic renal injury. After 5 min of ischemia, energy charge and ATP significantly decreased by 50% and 29% respectively. These parameters, however, did not significantly show the change in more than 5 min of renal ischemia. Energy charge and ATP did not reflect the degree of renal injury produced by ischemia, while it was indicated that the longer the period of ischemia until 120 min of ischemia, the less the rate of intrarenal ATP resynthesis at 30 min after reflow. Intrarenal lactate content increased significantly from the 5 min ischemia group to the 180 min. These results suggest that no improvement in intrarenal energy metabolism with increasing duration of renal ischemia is showed and ischemic renal injury develops progressively. It is probable that the decrease in U-NAG in severe ischemic renal injury is due to the inability of the kidney to wash out NAG into the urine, although NAG may be released from the injured tubular cells in proportion to ischemic renal injury. Therefore, in spite of severe ischemic renal injury, U-NAG may show low values, and may lead to misjudgement that the proximal tubular cells are intact. U-NAG should be measured repeatedly and estimated in association with the other renal function tests, especially creatinine clearance, for the correct evaluation of ischemic renal injury.

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The relationship between prostaglandin E₂ (PGE₂) receptor and GTP binding protein was studied in the normal and aminonucleoside-induced nephrotic rats. Affinities and maximal binding sites of PGE₂ receptors in renal medulla of the male Wistar rats were examined by Scatchard analysis. Cyclic AMP and inositol phosphates were measured in the medulla tissues to examine the intracellular mediators of PGE₂ receptor activation. The following results were obtained: 1) GTPγS, a nonhydrolyzable guanine nucleotide, increased the ³H-PGE₂ binding in a concentration-dependent manner, and pertussis toxin partially attenuated the GTPγS effect, 2) PGE₂ stimulated the accumulation of inositol phosphates in the medullary tissues with a similar dissociation constant (Kd) value of binding analysis, and high concentrations of PGE₂ stimulated the accumulation of cyclic AMP, 3) the affinity of PGE₂ receptors in the renal cellular membranes taken from nephrotic rats were significantly lower than that in normal rats, and the effects of GTPγS on the affinity was greater in nephrotic rat kidney than normal one. These results suggest that PGE₂ receptor of the rat kidney links to a GTP binding protein. In nephrotic rat kidney, damages occur not only in PGE₂ receptor but also in the GTP binding protein.

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Sairei-tô, one of the herb drugs, has been demonstrated to have several effects. Clinically, evidence have been accumulated showing that sairei-tô has been able to reduce the frequency of relapse in minimal change nephrotic syndrome. It has also found that sairei-to has improved proteinurial in minimal change nephrotic syndrome as well as chronic glomerulonephritis in man. Although the mechanism of such effects is still unclear, it is supposed that its immune modulative actions that has been reported In this study, we quantitated the number of intrarenal Ia positive cells and T cells in nephrotoxic nephritis in rats in order to clarify the intrarenal immune actions of sairei-tô on immune mediated glomerulonephritis. Four groups of rats with nephrotoxic nephritis were experimented on. The first group was the controlled group, had no treatment whatsoever. The second group was administed with MPSL (solu-medrol 20mg/kg, alternate day). The fourth group with both sairei-tô and MPSL. The level of proteinuria in three groups treated was almost the same, that is, less than that of controlled group. On light micoscopy, sairei-tô suppressed glomerular inflammation such as endocapillary proliferative lesions and mesangial expansion, which were shown in controlled group. The histological improvement was almost the found in rats treated with MPSL and both. Sairei-tô suppressed infiltrations of intraglomerular Ia positive cells (P<0.01) and T cells (P<0.01) on the 7th day and 14th day as well. Remarkable suppression of T cells infiltration was noted in rats treated with MPSL along with sairei-to on the 14th day (P<0.01). Moreover, while marked intraglomerular fibrin deposition was found in rats treated with MPSL, such a finding was not shown in rats treated with MPSL along with sairei-tô. These results suggested that sairei-tô may not possibly suppress only intraglomerular cell mediated immunity, but also hypercoagulability, both of which are known as renal deterioration factors in human glomerulonephritis. Therefore, the same could possibly be true in humam immune mediated glomerulonephritis.

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In order to clarify the abnomalities of cell-mediated immunity in patients with mesangial proliferative glomerulonephritis[IgA nephropathy (IgA N) and Non-IgA nephropathy(Non-IgA N)], lymphocyte subsets were analysed by using monoclonal antibodies with flow cytometric two-color analysis and interleukin-2 (IL-2) production from lymphocytes of the patients was measured by ELISA system. A markedly decreased percentage (11.6±10.5%) of CD4⁺ 45R⁺ cells was found in the patients with IgA N when the results were compared with the normal controls (20±6%) (P<0.01). No difference was found between patients with IgA N and the controls as to the percentage of CD4⁺ 45R^-, CD8⁺, 11⁺ and CD8⁺ 11^- cells, respectively. Patients with Non-IgA N also showed a significantly decreased percentage of CD4⁺ 45R⁺ cells (10.9±6.5%), while CD8⁺ 11⁺ cells was parallely lowered (7.4±5%) in compared with the controls (10±4%). The percentage of HLA-DR positive cells was found to be increased in the patients with both IgA N and Non-IgA N, although the antigen bearing cells were reduced after stimulation with Concanavalin-A (Con-A). No diffrence in IL-2 production from lymphocyte of both patients groups and the controls cultured with Con-A was found. These results suggested that a deficiency of suppressor inducer T cells played a part of the pathogenesis of IgA N and Non-IgA N.

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Comparative studies of clinicopathological findings were carried out in 89 patients with adult and juvenile onset of IgA nephropathy Among 89 patients with IgA nephropathy, there were 42 patients with juvenile onset, i.e less than 19 years old, and 47 patients with adult onset, i.e. more than 35 years old. Clinical activities of both groups were examined as follows; urinary protein, mean blood pressure renal function (PSP 15 min, Ccr) and serum IgA (s-IgA). The histology of renal tissues was also examined by light microscopy and immunofluorescence in both groups. The levels of mean blood pressure or s-IgA in patients with adult onset group were significantly higher than those in patients with juvenile onset group (p<0.01). The levels of Ccr in patients with adult onset group were markedly decreased. The patients with more than 1.0g/day of proteinuria and more than 110 mmHg of mean blood pressure showed severe proliferative glomerular injuries by light microscopy. It is suggested that the patients with adult onset of IgA nephropathy show severe progressive and/or exacerbating factors during the clinical course.

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Discriminant analysis of clinical markers before renal biopsy in patients with IgA nephropathy is described. Sixty eight patients with IgA nephopathy (IgA nephropathy group) and 66 patients with other chronic glomerulonephritis (non-IgA nephropathy group) were examined. The discriminant analysis was applied to separate those .two groups by using twenty clinical parameters as well as binding capacity of serum IgA to the glomeruli of renal specimens. Binding of serum IgA of patients to the glomeruli obtained from patients with IgA nephropathy was performed using avidin-biotin immunofluorescence. Among twenty clinical markers, the levels of serum IgA and creatinine, and degree of microhematuria in IgA nephropathy group were significantly higher than those in non-IgA nephropathy group Furthermore, the positive incidence of serum IgA binding of IgA nephropathy group was significantly higher than that of serum IgA binding of non-IgA nephropathy group. The correct classification rate were 79.10% using five clinical markers including serum IgA, microhematuria, serum C4, quantitation of proteinuria and degree of proteinuria. It is indicated that the levels of serum IgA and the binding of serum IgA to the glomeruli were considered to be major markers for clinical diagnosis of patients with IgA nephropathy It was concluded that the discriminant analysis before renal biopsy was useful for diagnosis of IgA nephropathy

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Systemic lupus erythematosus (SLE) is a disease of unknown etiology in which many organs are damaged by deposition of pathogenic autoantibodies and immune complexes Clinically lupus nephritis occurs about 50% in SLE Many studies revealed the association between autoantibodies and lupus nephritis However, the pathogenetic role of autoantibodies in lupus nephritis remains obscure. To elucidate the pathogenetic role of anti-SSA antibody in lupus nephritis, 32 patients with SLE were evaluated by serological and histological methods. Enzyme-linked immunosorbent assay for anti-SSA antibody was developed for this study. It was confirmed that this assay was specific, did not detect autoantibodies other than anti-SSA antibody. The levels of anti-SSA antibody determined by this assay significantly correlated with the levels determined by double immunodiff usion (p<0.01). The level of anti-SSA antibody greater than or equal to 200 units was regarded as positive. The serum levels of antinuclear antibody, anti-DNA antibody, anti-RNP antibody, anti-SSA antibody, anti-SSB antibody, C3, and C4 were also determined. Renal biopsy materials were evaluated according to the WHO criteria, and activity index (AI), chronicity index (CI), and pathologic score (PS) were calculated according to Austin et al. The patients were divided into group A (AI>4, n=17) and group B (AI<3, n=15) The levels of anti-DNA antibody were significantly higher in group A than in group B (p<0.05). The frequency of positive anti-SSA antibody in group A (70.6%) was greater than in group B (23.3%) significantly (p<0.05) However, there were no differences in the levels of anti-nuclear antibody, anti-DNA antibody, anti-RNP antibody, anti-SSA antibody, anti-SSB antibody, C3, and C4 between group A and group B. Then these patients were divided into group I(anti-SSA>200 units, n=17) and group II(anti-SSA<200 units, n=15). AI and CI were greater than in group I than in group IIsignificantly (p<0.05). The frequency of pericarditis in group I (35.3%) was greater than group II (6.7%) (p=0.061), but the frequencies of the other clinical manifestations were not different. AI was correlated with anti-DNA antibody significantly (p<0.01), but there were no correlations between other serological data and parameters. From these data it is suggested that anti-SSA antibody could be involved in the pathogenesis of lupus nephritis.

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In order to investigate the pathogenesis of renal anemia, erythroid marrow cellularity, factors affecting erythropoiesis and hemolysis, hemolysis starting point by Parpart method and red cell life-span were studied in 21 patients undergoing hemodialysis (HD). Mean value of serum erythropoietin level (EPO) in HD patients was 28.4 mU/ml, which value was nearly equal to that in healthy subjects. Total erythroblast count was higher than normal up to 25.2% in HD patients with Ht below 25% (A group), on the other hand, in HD patients with Ht above 25% (B group) it was 216%, nearly equal to normal. Total erythroblast counts positively correlated to EPO level, but did not correlate to ribonuclease, aluminium and parathyroid hormone. Red cell life-span was 23.4 days in A group, and it was 19.8 days in B group Hemolysis starting point was observed at 0.61% NaCl in B group, and at 0.56% in A group. Hemolysis starting point negatively correlated to red cell life-span, but did not correlate to BUN, serum creatinine and serum guanidino compound. Hb level negatively correlated to nuclear cell counts of bone marrow in HD patients, and positively correlated to hemolysis starting point. These results suggested that erythroblast count was controlled by both erythropietin and hemoglobin levels in HD patients. Hemoglobin level in HD patients was maintained by balance of counteracting factors between erythropoeisis and hemolysis.

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Echocardiography was studied in 83 uremic patients on maintenance hemodialysis and 18 normal subjects. Cardiac systolic and diastolic functions were evaluated according to Yamaguchi's method. Systolic functions such as ejection fraction and fractional shortening decreased in the patients receiving hemodialysis for less than 3 months. However, they remained within normal range in the patients under hemodialysis for more than 3 months. There were no significant correlations between systolic functions and mean blood pressure or vaious serum biochemical parameters such as urea nitrogen, creatinine, Na, K, Ca, P, hematocrit and PTH-C. Diastolic functions such as rapid filling rate/endosystolic volume, mean velocity of circumferential fiber lengthening during rapid filling, diastolic descent rate and diastolic posterior wall velocity also decreased in the patients receiving hemodialysis for less than 3 months. However, they increased slightly in the patients under hemodialysis for more than 3 months, although they were still lower than those in normal subjects. They were not related to mean blood pressure or various serum biochemical parameters. Hemodialysis patients had left ventricular hypertrophy regardless of duration of hemodialysis. Diastolic dysfunction in hemodialysis patients seemed to be due to systolic dysfunction, left ventricular hypertrophy and diminished ventricular compliance with myocardial degeneration. It was also suggested that increasing slow filling and atrial contraction in diastole might be related to diastolic dysfunction These cardiac changes may be compensatory reactions of cardiac muscle to various uremic environments such as anemia, hypertension, fluid retention, electolytes disturbance or uremic toxins.

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The present study aimed to elucidate the role of Na, K-ATPase inhibitor in renal sodium metabolism in essential hypertension. Mean arterial pressure(MAP), heart rate(HR), urine volume(UV), urinary excretion of sodium(U_NaV), endogenous creatinine clearance(Ccr), fractional excretion of sodium (FE_Na), plasma renin activity(PRA) plasma aldosterone concentration(PAC), plasma noradrenaline concentration (PNA) and urinary excretion of noradrenaline (UNA) were measured before and after intravenous injection of ouabain (0.1mg/m²·BSA) in 12 normotensive (NT) and 22 mild-to-moderate essential hypertensive subjects (EHT). Following ouabain injection, UV, U_NaV FE_Na significantly increased, but PRA decreased, in both NT and EHT. MAP, HR, Ccr, PNA, and UNA did not change significantly in either group. On the other hand, a significant decrease in PAC was observed in NT, but not in EHT. The changes of U_NaV and FE_Na were significantly attenuated in EHT as compared to NT. No significant difference in change of MAP, HR, UV, Ccr, PNA, UNA, or PRA was demonstrated between NT and EHT. A significantly positive correlation was found between ΔU_NaV and ΔFE_Na in both NT and EHT, while no significant correlation was observed between ΔU_NaV and ΔMAP, ΔUV, ΔCcr, ΔPRA, ΔPAC, ΔPNA and ΔUNA in either group. These results suggest that 1) Na, K-ATPase inhibitor clearly augments natriuresis by suppression of sodium reabsorption in renal tubules, 2) since this augmentation was attenuated, there is an elevation of endogenous Na, K-ATPase inhibitor(s) should be considered in EHT, and 3) an increase of the inhibitor might participate to the hypertensive mechanism in EHT.

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From April 1986 to March 1988, 7, 800 subjects (3, 887 men and 3, 913 women, age from 24 to 80 years, with a mean age of 48.7 years) underwent renal ultrasound during a screening by our Health Survice. Of these sujects 29 were suspected to have solid masses in the kidneys. Further examination with computerized tomography (CT) was employed. Four angiomyolipomas and 16 malformations of the kidneys were diagnosed clinically at that time. Among 9 subjects who underwent complete urological evaluation including excretory urography (IVP), CT and renal angiography 6 malignant renal tumors were disclosed. Six patients were treated by radical nephrectomy. In this report we studied the 6 patients whose tumors were pathologically diagnosed as renal cell carcinoma (RCC). The six patients were 48 to 60 years old with a mean age of 55.8 years There were 4 men and 2 women. There are no signs or symptoms referable to RCC In 1 patients microscopic hematuria was deteced via a laboratory study . Erythocyte sedimentation rate (ESR) was slightly elevated in 4 patients. In the 6 patients, the renal tumors were diagnosable by CT and all tumors had positive findings for malignant neoplasms angiographically An IVP, without nephrotomography, did not reveal a small tumor growing in the upper pole of the right kidney of 1 patient. Surgical specimens were 180-475 g in weight. Tumors, were found in the right kidneys (2) and in the left kidneys (4), were well circumscribed. The size of the tumors measured from 3 to 7 cm in the longest axis . Pathological diagnosis was made as renal cell carcinoma 3 with G1, pT2a, 2 with G2, pT2a and 1 with G2, pT2b. The value of routine renal ultrasound in over-all health screening are discussed

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A 83-year-old male patient with IgD myeloma associated with renal amyloidosis and acute renal failure is described. We also reviewed the clinicopathological findings of IgD myeloma in the literature. Although hemodialysis was performed 36 times for acute renal failure, he died of severe gastrointestinal bleeding. Renal necropsy specimens revealed typical features of amyloidosis in light microscopic, electron microscopic and immunofluorescent examinations. The levels of serum IgD (755 mg/dl), immunoelectrophoresis, and immunofluorescence of bone marrow and renal specimens were consistent with IgD myeloma (λ type). IgD myeloma is generally considered to be a rare disease of juvenile onset and is complicated with extramyelogenic tumors according to previous reports. However, IgD myeloma without extramyelogenic tumors occurred in a 83-year-old patient reported here It appears that advanced age onset IgD myeloma associated with renal amyloidosis and acute renal fialure is rare This was the oldest case of IgD myeloma we examined.

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