The present study was carried out to clarify the mechanism of elevation of glomerular filtration rate (GFR) induced by synthesized α-human atrial natriuretic peptide (α-hANP) employing isolated perfused rat kidney (IPRK) maintained with a rather low perfusate flow. In addition, the binding sites of synthesized rat ANP (rANP) in the kidney were investigated. Despite the reduction in perfusion flow rate, the renal perfusion pressure (RPP) was temporarily reduced to 87.00 ± 7.01 mmHg from 92.38 ± 5.23 mmHg (p<0.1) within 5 min after the injection of a-hANP. This finding apparently suggested that α-hANP behaves as an accelerator of vasorelaxation mediated by a myogenic network mechanism. Also CIn was significantly increased to 0.24 ± 0.02 ml/ min/g (P<0.01) from 0.11 ± 0.01 ml/min/g. The increase in CIn following injection of α-hANP appeared to be accompanied by significant increases in urinary volume (0.12 ± 0.01 from 0.06 ± 0.02 ml/min/g, p < 0.01), CPAH (1.48 ± 0.09 from 0.44 ± 0.05 ml/min/g, p <0.001), and FENa (0.32 ± 0.07 from 0.21 ± 0.03, p < 0.005). After these changes, RPP gradually increased to reach 116.16 ± 9.54 mmHg (p < 0.005) at 15 min after the injection of α-hANP, and this was subsequently followed by remarkable increases in urine volume, CIn, CPAH, FENa and FEK. On the other hand, immunoreactive rat-ANP (IR-rANP) showed for more marked staining on the glomerular afferent arterioles compared to the efferent arterioles at 10 min after rANP exhibited its own renal effects. In conclusion we propose the hypothesis that injection of α-hANP primarily induced an elevation of the GFR by increasing the vascular permeability of the glomerular capilary wall and then a vasodilating effect on the glomerular afferent arterioles with vasoconstriction of the efferent arterioles.

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The levels of IgA, secretory-IgA (s-IgA) and free secretory component (FSC) in pharyngeal washings were examined in patients with IgA nephropathy, other glomerular diseases and healthy adults. The levels of IgA or s-IgA in the pharyngeal washings were significantly increased in patients with IgA nephropathy or other glomerular diseases as compared to those in healthy adults. There was a significant correlation between the levels of s-IgA and those of IgA and FSC in the pharyngeal washings from patients with IgA nephropathy. Infections of the upper respiratory tract within one year prior to the present study were more frequent in patients with IgA nephropathy than in those with other glomerular diseases. It is suggested that the mucosal resposise of the upper respiratory tract may be hyperreactive in patients with IgA nephropathy.

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Kidney biopsy specimens obtained from 4 non-nephrotic patients with hyperlipidemia showed the histology of focal glomerular sclerosis (FGS). One young patient had demonstrated protein-uria since the age of 15. He was obese and revealed genital malformation. However, his familial history was unremarkable for hyperlipidemia. The other 3 were found to have proteinuria in their thirties and underwent renal biopsies. The proteinuria was not so heavy as to induce hypoalbuminemia in all patients. They had no edema. The observed lipoprotein abnormalities were classified as type IV on the WHO classification in 2 patients and type V in one patient. On light microscopy, the focal segmental sclerotic lesions with hyaline deposits were identical to those generally seen in nephrotic patients. Glomerular IgM and C3 deposition was demonstrated in all patients except one in whom only C3 were deposited. The prognosis was rather poor. Renal function was deteriorated in 3 patients. One of them was sufficiently aggravated as to require hemodialysis. The other patient died of myocar-dial infarction. It is suggested that lipid toxicity may play an important role in the development of sclerosis in such non-nephrotic and hyperlipidemic patients, because other injurious factors causing nephrotic syndrome, i.e., hemodynamic abnormality or hypoalbuminemic hypercoagulability, do not operate. The role of lipids is supported by some experimental evidence in hyperlipidemic animals which displayed glomerular sclerosis.

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The serum and urinary β₂-microglobulin (β₂m) levels were measured in 11 patients with chronic glomerulonephritis (CGN), 7 patients with pure toxemia of pregnancy, and 7 healthy women during pregnancy and after delivery. In the toxemic patients, the serum β₂m was significantly higher than that in the other two groups at 34-36 weeks of gestation (wks). The urinary total β₂m and fractional β₂m excretion (FEβ₂m) were also the highest among the three groups at the third trimester in the toxemic gravida, but there were no significant differences. The FEβ₂ m and daily urinary protein excretion were closely correlated (r= 0.915, p<0.001) in the patients with CGN and pure toxemia groups who had proteinuria levels of above 1 g/day. Although we found very high levels of serum and urinary β₂m in the pure toxemic gravida, we were unable to differentiate toxemic syndrome due to CGN from pure toxemia on the basis of the level of β₂m.

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A total of 269 cases of urinary stone colic occurring within a basin in central Japan was studied in relation to the climatic condition. The incidence was high in the hot season. Factors which caused small stones in the renal pelvis to initiate colic were analyzed. Days of falling atmospheric pressure were associated with a high incidence of colic and days of rising pressure with a low incidence . Falling temperature provoked colic in the cold season. In the hot season, days with a rising temperature were not associated with a high incidence, probably because the summer is cool in this area.

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In adenine-administered rats, urine volume increased gradually with the progress of renal dysfunction to polyuria, but the amounts of urea, creatinine (Cr), guanidinosuccinic acid (GSA) and guanidinoacetic acid (GAA) excreted into the urine showed a significant decrease throughout the experimental period. In contrast, excretion of methylguanidine (MG) was markedly increased. The glomerular filtration rate (GFR), renal plasma flow (RPF) and renal blood flow (RBF) decreased progressively as the renal impairment increased due to prolonged administration of adenine.

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In rats with chronic renal failure induced by adenine, the level of methylguanidine (MG) was significantly increased and could be detected in the cardiac muscle, liver, skeletal muscle, small intestine, kidney and serum; guanidinosuccinic acid (GSA) was detected in the liver, kidney, and serum. The amounts of MG and GSA which accumulated in the body increased according to the number of days of adenine feeding. In contrast, the level of guanidinoacetic acid (GAA) became decreased in the kidney, serum, and then the skeletal muscle. No remarkable changes in these levels were recognized in the brain.

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In rats given an adenine diet, marked changes were observed, such as a fall in renal blood flow, increase in blood pressure, partial activation of the renin-angiotensin-aldosterone system, and reduction in the prostaglandin E₂ level, resulting in renal hypertension.

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In order to estimate the exposure levels of mutagenic and carcinogenic heterocyclic amines in humans, we determined 2-amino-3-methylimidazo [4, 5-f] quinoline (IQ), 2-amino-3, 4-dimethylimi-dazo [4, 5-f] quinoline (MeIQ) and 2-amino-3, 8-dimethyl imidazo [4, 5-f] quinoxaline (MeIQx) by high-performance liquid chromatography. The dialysis fluid of 10 patients who had received con-tinuous ambulatory peritoneal dialysis was examined by this method. The amounts of IQ, MeIQ and MeIQx in the total dialysate (about 6 liters) per day were 300.8 ± 71.3 pmole, 334.6 ± 113.9 pmole and 322.5 ± 132.8 pmole (mean ± S.D., n = 10), respectively. The mean recoveries of IQ, MeIQ and MeIQx by our assay method were 66.1%, 62.5% and 65.2%, respectively. These results indicated that patients with uremia are actually exposed to carcinogenic IQ-type heterocyclic amines. Based on the recoveries, the total exposure level of IQ-type heterocyclic amines (IQ, MeIQ plus MeIQx) in the uremic patients was estimated to be about 1500 pmole per capita per day.

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Cases without glomerular deposition of C3c in spite of deposition of immunoglobulin are known to occur in membranous nephropathy or IgA nephropathy. When the deposition of C3d as a C3 breakdown product or H as a control protein was investigated by immunofluorescence in such cases, depositions of C3d and H were found in all cases. From the results obtained, it is considered that C3 underwent decay due to the action of control protein, etc., and was converted to C3d in spite of the involvement of complement at that localization in the kidneys.

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The clinical findings and histological changes in the kidney of a patient with IgA nephropathy complicated by poststreptococcal acute glomerulonephritis are described. The histological diangosis at the first renal biopsy was focal segmental glomerulonephritis. Seven years later, acute nephritic syndrome occurred after a latent period of 11 days following acute pharyngitis. A second biopsy was performed and diffuse global mesangial and endocapillary glomerulonephritis with crescent formation was diagnosed. Since both the antistreptolysin-O and antistreptokinase titers were rising and typical "humps" were observed by electron microscopy, this episode was concluded to be due to poststrepto-coccal acute glomerulonephritis. Reexamination of the first biopsy specimen by an unlabelled peroxi-dase-antiperoxidase method demonstrated .widespeared distribution of IgA in the mesangium. The present patient was thus a very rare case of IgA nephropathy complicated by poststreptococcal acute glomerulonephritis.

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A 43-year-old male developed anasarca, pulmonary edema and severe hypertension in the acute phase of poststreptococcal glomerulonephritis, Vigorous treatment of the anasarca with intravenous furosemide and of the hypertension with multiple antihypertensive drugs failed to control the intra-vascular volume overload and severe hypertension. The patient subsequently developed cerebral hemorrhage. The severe hypertension was controlled only by intravenous diazoxide. Reports of intracranial hemorrhage in acute poststreptococcal glomerulonephritis are very rare but the prognosis is poor. Aggressive antihypertensive therapies including diazoxide are recommended when the blood pressure is not controlled by diuretics and conventional anti-hypertensive drugs.

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Based on the distribution and intensity of fibrin related antigen (FRA) in the glomeruli, we devised an FRA index in patients with IgA nephropathy. The patients already had moderately or severely affected renal function at the time of renal biopsy. The group of patients with an FRA index of less than 2.0 revealed no significant changes in renal function during the subsequent 2 years. On the other hand, the patients with an FRA index of more than 5.0 showed significant deterioration of renal function. Among the patients with an FRA index of between 2.0 and 5.0, 8 of 10 patients (80.0%) treated with antiplatelet drug alone and 5 of 13 patients (38.5%) under warfarin and anti-platelet therapy revealed a significant decrease of renal function in terms of the reciprocal creatinine values by linear regression, respectively. Among the patients having both a controlled period and treated period in their courses, 5 patients showed an FRA index of 2.0 to 5.0. Although singificant improvement of renal function was seen in only one patient during the treatment period, steeper deterioration of renal function during the treatment period as compared to the control period was not observed in these 5 patients. These results suggest that the FRA index may be useful as a prognostic index and that warfarin was effective in some patients with IgA nephropathy, particularly those with an FRA index of 2.0 to 5.0.

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Intraglomerular coagulation and fibrinolysis were examined in vitro and in vivo in 50 patients with IgA nephropathy, Deposition of alpha 2-plasmin inhibitor (α2-PI) was prominent in glomeruli of patients with IgA nephropathy. There was a significant correlation between the incidence of α2-PI deposition and that of fibrinogen deposition in the glomeruli from such patients. These findings were associated with advanced histopathological changes such as capsular adhesion or crescent for-mation. It appeared that deposition of α2-PI might strongly inhibit fibrinolysis in the glomeruli for a long period in patients with IgA nephropathy. Clinical improvement in the degree of proteinuria, microscopic hematuria and the levels of serum creatinine was significantly noted after 'single shot' administration of urokinase (UK). Such improvement was significant in patients with 'consecutive' UK administration for 22 months compared with those with 'two weeks' UK administration. It was evident that 'consecutive' UK treatment could ameliorate renal injuries in patients with IgA nephropathy.

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The correlation between the severity of morphologic changes in the glomerular basement mem-brane (GBM) and clinical features was investigated in 28 patients with idiopathic membranous nephro-pathy (IMN). Morphologic changes in the GBM were photographed by electron microscopy to measure the area of electron dense deposits (D.D.) in the subepithelium and of the original basement membrane (B.M.). The ratio between these areas (D.D./B.M.(%)) was then calculated. A significant positive correlation (r 0.76) was noted between the D.D./B.M. ratio and the amount of urinary protein discharged daily, indicating that the degree of lesions in the GBM was proportional to the degree of proteinuria. Using polyethylene imine, the disappearance and disarrangement of anionic sites in the GBM was observed in regions where immune complex deposition was significant. The results obtained suggested that the deposits in the GBM might cause a reduction of the number of anionic sites and destruction of the charge barrier, so that massive proteinuria followed clinically. The present findings indicate that the D.D./B.M, ratio might represent a useful parameter for evaluating not only the degree of morphologic changes but also some of the clinical features, especially the degree of proteinuria, in patients with IMN.

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