IgM and IgG rheumatoid factors (RF) were measured by radioimmunoassay in 25 serum and 10 urine samples of patients with idiopathic membranous nephropathy (MN), 29 sera of systemic lupus erythematosus (SLE), 29 of rheumatoid arthritis (RA) and 29 of normal controls. Significantly low levels of IgM-RF and IgG-RF were detected in the sera of MN patients (P<0.02, P<0.05), whereas the IgM-RF levels were significantly high in the sera of RA patients. The 17 MN patients with nephrotic syndrome showed significantly low levels of serum IgG-RF (P<0.05) and IgM-RF (P<0.01), in comparison with 10 nephrotic controls (minimal change, 6; diabetic nephropathy, 4), There was no evidence that serum RF of nephrotic patients with MN flowed out in the urine. A good correlation was obtained between IgG- and IgM-RF in the sera of MN patients. The immune complexes (IC) of IgG class, detected in MN patients' sera by solid phase Clq (ClgSP) binding assay and solid phase conglutinin (KgSP) binding assay, were compared with the levels of serum IgG-RF. No patients sera showed higher than the normal range of IC levels by ClgSP assay, and only 5 of 25 sera (20%) revealed higher levels by KgSP assay. The levels of IgG-RF showed an excellent correlation with the amounts of SPClq-IC (P<0.001), and a relatively good correlation with those of SPKg-IC (P<0, 02). These data may support the immunopathological background of MN, i.e. suppressed production or accelerated clearance of antibodies including RF.

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A patient with chance proteinuria, who presented very interesting clinico-pathological features, is described. This case with quite mild proteinuria as the only renal symptom, had hypocomplementemia serologically from an early stage. Morphologically, a mild increase in mesangial cells and matrix, and thickening of the glomerular capillary basement membrane were revealed by light microscopy. By im-munofluorescence, coarse granular deposits of only C3 were found in the mesangial areas. Ultrastructural studies demonstrated irregular intramembranous granular dense deposits. It is suggested that this case, with a strikingly mild clinical course without worsening of the urinary findings and decrease of renal function, in addition to the above morphological features, had membranoproliferative glomerulonephritis type II with atypical intramembranous dense deposits.

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Prednisolone and cyclophosphamide were administered to 17 patients (12 male and 5 female) with IgA nephropathy for 6-12 weeks (8 weeks on average). The results showed an improvement in urinary findings in 10 cases (9 males and 1 female), and recurrence or ineffectiveness in 7 cases (3 males and 4 females). The duration from the start of concomitant administration of both drugs to improvement in the urinary findings ranged between 1 and 36 weeks (22 weeks on average). On light microscopy, no correlation was found between the degree of changes in the renal tissues and the therapeutic effects. The fluorescent findings revealed that as a result of administration of the two drugs, improvement in urinary findings was present in 9 (75%) of 12 cases where IgA was mainly demonstrated in the stylobasal membrane of the glomerulus, but this regimen was effective in only 1 (20%) of 5 cases where IgA was observed chiefly as masses in the mesangium. Renal biopsy was performed twice, before and after the treatment, in 8 of the 17 cases. Improvement in urinary findings and disappearance of IgA in the renal glomerulus were observed in 2 cases, while IgA positive findings continued even after improvement of the urinary findings in 4 cases. The urinary findings and histologic findings were unchanged in the remaining 2 cases.

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The prognostic significance of mesangial sclerosis was analyzed in IgA nephropathy. Mesangial sclerosis was evaluated histologically in biopsied specimens based on its grade and distribution (mesangial sclerosis index, MSI). The index was compared with the creatinine clearance (Ccr) at the time of biopsy. The results indicated that patients whose mesangial sclerosis index exceeded 0.5 and whose Ccr was under 90 ml/min showed an unfavorable course as determined by the Ccr at 2 years after the second biopsy. Comparative analysis of mesangial sclerosis in biopsy specimens and renal function at the time of biopsy is thus considered valuable for assessing the prognosis of patients with IgA nephropathy.

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The effect of 1α-hydroxyvitamin D₃ (1α-OH-D₃) on the skeletal muscle of uremic rats was studied. In order to induce uremic changes, 70% of the left kidney was damaged by electrocoagulation and right nephrectomy was subsequently carried out. Control animals were sham operated and pair-fed. Two weeks after the operation, the uremic animals were divided into 2 groups, one of which was given 1α-OH-D₃ and the other was untreated. Biochemical data and pathological findings for the gastrocnemius muscle and sciatic nerve were compared between the 3 groups at 6 weeks after the operation, the untreated uremic animals, there was a significant (P<0.02) elevation of serum creatine phosphokinase (CPK) values, atrophy of all types of muscle fibers, with a relative decrease in the number of type II fibers, and no patholoogical changes in the peripheral nerves as compared to the controls. These biochemical and morphological changes in uremia were thought to represent primary muscle damage, and administration of 1α-OH-D₃ was effective not only in suppressing the elevated serum CPK levels but also in suppressing the development of morphological muscle changes.

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Two sisters received long-term hemodialysis to manage chronic renal failure resulting from treatment of their cystinuria. Both had progressive renal failure caused by D-penicillamine treatment after surgery for urolithiasis. These are the first reported cases involving sisters. The 34-year-old sister had received dialysis since April 1975 and her 26-year-old sister had been on dialysis since October 1977. There has been little variation in the treatment of chronic renal failure whether caused by cystinuria or by other diseases. However, we treated these sisters with cystinuria, along with other patients, by differential diet management. The balance of plasma amino acids improved remarkably after 3.5 years of treatment and both sisters are now undergoing excellent dialysis. The diet restricts methionine and crystine to 2.5 g/day.

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The effects of the angiotensin converting enzyme inhibitor, captopril, on renal function and serum electrolytes were studied in 29 hypertensive patients with normal and impaired renal function. After 5 to 27 days (12.3 ± 0.9, Mean ± SE) of treatment with 50 to 200 mg/day (89.7 ± 6.4) of captopril, 10 patients (Group I) with normal renal function as indicated by a creatinine clearance (Ccr) of more than 70 ml/min showed no change in either renal function or serum electrolytes (sodium and potassium). Another 10 patients (Group II) with mildly impaired renal function (50 ml/min ≤ Ccr 70 ≤ml/min) revealed no effect on renal function but had an increased serum potassium level (from 4.0 ± 0.2 to 4.4 ±0.1 mEq/l, P <0.05). The remaining 9 patients (Group III) with moderately to severely impaired renal function (Ccr <50 ml/min) had deterioration of renal function (from 39.2 ± 3.0 to 30.3 ± 3.8 ml/min, P <0.01) and had an increased serum potassium level (from 4.2 ± 0.2 to 4.9 ± 0.3 mEq/l ; p <0.05). There was no correlation between deterioration renal function and reduction of mean blood pressure in any single group or in the total group of subjects. In patients with considerably impaired renal function, a decrease of renal plasma flow associated with a decrease of blood pressure and the renin-angiotension system in the kindney might play a critical role in the maintenance of the glomerular filtration rate. There were weak, but statistically significant, inverse correlations between the change in serum potassium and that in plasma aldosterone concentration (PAC; r=-0.45, P <0.05) and between the pretreatment Ccr and change in serum potassium (r=-0.74, P <0.01). These results suggest that the hyperkalemia produced by captopril administration may be due to the potassium-retaining tendency of renal insufficiency and in part to the reduction of PAC. During captopril treatment, renal function and serum potassium should be closely monitored in patients with impaired renal function.

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The present study was undertaken on 12 hypetensive patients to compare the acute effects of three structurally different converting enzyme inhibitors (CEIs) on blood pressure, the renin-angiotensin system and the kallikrein-kinin system. Each drug (25 mg captopril, 5 mg SA-446 or 5 mg MK-421) was given orally on separate days. All three CEIs exerted potent hypotensive effects. The maximal fall in mean blood pressure (MBP) occurred at 2 h, 1 h and 12 h after administration of captopril, SA-446 and MK-421, respectively, with MK-421 exhibiting the most prolonged depressive effect. A positive correlation was observed between the reduction in MBP by the three CEIs and the pretreatment level of plasma renin activity (PRA; r=0.51, P <0.005) and plasma bradykinin (BK; r = 0.61, P <0.005). There were significant correlations between the reduction in MBP and the increase in BK by captopril (r=-0.73, P <0.01) and SA-446 (r=-0.67, P <0.01). However, a similar correlation was unexpectedly not observed in the case of MK-421. The antihypertensive action of CEIs appears to be linked to the accumulation of BK as well as inhibition of the conversion of angiotensin I to angiotensin II. However, MK-421 may differ slightly from captopril and SA-446 in its effect on the hypotensive role of BK.

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The acute and chronic effects of captopril on the renin-angiotensin and kallikrein-kinin systems were studied in Wistar-Kyoto rats (WKY), spontaneously hypertensive rats (SHR) and stroke prone-SHR (SHR-SP). In the acute study, captopril (100 mg/kg) reduced the mean blood pressure after 60 min by 2.7 ± 2.4% (not significant) in WKY, by 7.5 ± 1.0% (P<0.01) in SHR and by 13.9 ± 2.9% (P<0.01) in SHR-SP. The plasma renin concentration (PRC) in the groups administrated captopril was significantly higher than that in the control groups in all three strains of rats. The plasma bradykinin (BK) in the groups administrated captopril was also higher than that in the control groups, although a significant difference (33.4 ± 6.3 pg/ml vs. 16.9 ± 2.2 pg/ml; P <0.05) was observed only in SHR-SP. In the chronic study, captopril (0.4 mg/ml in tap water, for 10 weeks) significantly (P <0.001) reduced the systolic blood pressure in SHR, SHR-SP and even in WKY compared to the control groups. The PRC in the groups treated with captopril was significantly higher than that in the control groups in all three strains of rats. However, no significant increases were seen in BK. The urinary sodium excretion was greater in the captopril groups than in the control groups in WKY (3.15 ± 0.13 mEq/day/kg vs. 1.83 ± 0.20 mEq/day/kg; P <0.001), SHR (3.16 ± 0.32 mEq/day/kg vs. 1.94 ± 0.33 mEq/day/kg; P <0.001) and SHR-SP (2.50 ± 0.41 mEq/day/kg vs. 2.15 + 0.34 mEq/day/ kg; not significant). These results suggest that BK accumulation may contribute partially to the hypotensive role of captopril in the acute phase, but not in the chronic phase. Long-term administration of captopril potentiates natriuresis and diuresis, which might also contribute to its hypotensive role in the chronic phase.

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Angiotensin converting enzyme inhibitor (CEI, captopril) and angiotensin II analogue (AIIA) were administered in 63 hypertensive patients with various etiologies. Following CEI administration, there was a significant reduction of diastolic blood pressure (DBP) in all types of hypertension. However, with AIIA infusion, DBP was increased in essential hypertension and decreased in renovascular hypertension and malignant hypertension in which the plasma renin activity (PRA) was high compared to essential hypertension. There was a significant correlation between the changes in DBP and PRA with CEI or AIIA in subjects with essential hypertension. This suggests that secretion of renin is related to change of blood pressure, presumably due to altered intrarenal baroreceptor stimulation and/or sympathetic activity via baroreceptor, while it is not negligible due to interruption of the negative short feedback loop through which angiotensin II regulates renin release. There was a correlation between the percent changes in DBP induced by CEI and AIIA which have different mechanisms for inhibition of the renin-angiotensin system. After sodium depletion, the pressor effect of AIIA was blunted and the depressor effect of CEI was pronounced, while the control PRA increased significantly. We conclude that these two different agents can be useful clinically for evaluating the factor of the renin-angiotensin system in hypertension if responses to them are interpreted in relation to the sodium balance and baseline PRA. In essential hypertension, "high-responders", highly responding subjects in the secretion of aldosterone to intravenous administration of furosemide following one-hour upright posture, showed a larger reduction in plasma aldosterone concentration with CEI than "low-responders" This suggests that there may be two subgroups of essential hypertensives in aldosterone secretion mediated by the renin-angiotensin system. Hyperreninemia in the control period and after CEI or AIIA administration and a larger change in PRA with CEI were observed in renovascular hypertension as compared to essential hypertension or renal hypertension. These results suggest that a combination of control PRA measurement and blocking tests of the renin-angiotensin system with CEI and AIIA can provide a useful screening procedure for the diagnosis of renovascular hypertension.

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To investigate the role of the nucleus locus coeruleus (LC) in the prehypertensive stage, the responses of the hemodynamics, plasma norepinephrine concentration (PNE) and renal sympathetic nerve activity (RSNA) to electrical stimulation and lesioning of the LC were studied in the prehypertensive stage of DHR. The basal RSNA was greater in the prehypertensive DHR than in the normotensive stage demonstrated an increased PNE in response to LC stimulation. The DHR LC pressor thres-hold current (PTC) was lower in the prehypertensive stage than in WKY. The pressor responses to i.v. norepinephrine were not different between DHR in the prehypertensive stage and WKY. Following lesions of the bilateral LC, the mean arterial pressure (MAP) and DHR RSNA in the prehypertensive stage were decreased more than in WKY. The DHR LC in the prehypertensive stage may thus affect the hyperactivity in the sympathetic nervous system and may be involved in the occurrence of hyper-tension in DHR.

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An experimental urolithiasis induced by dietary adenine in rats is reported. The principal component of the stone was proved to be 2, 8-dihydroxyadenine by ultraviolet spectroscopic analysis, infrared spectroscopic analysis, and mass spectrometric analysis.

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Computerized tomography (CT) without injection of contrast medium was employed to detect the presence of very small calculi which were faintly opaque or nearly lucent on plain film of the abdomen. These small calculi regardless of their components were invariably dense on CT. This technique is therefore useful for diagnosing faintly opaque and/or small calculi which are not diagnosed on conventional radiological examinations.

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The anti-albuminuric effect of dilazep was studied in aminonucleoside (AN)-induced nephrotic rats. The drug was administered to the animals orally in 2 divided doses 4 weeks prior to AN injection. Urine was collected daily to measure the 24-hour albumin excretion and also the creatinine clearance rate. AN injection induced marked albuminuria in both animals treated and untreated with dilazep. However, the albuminuria in the drug-administered rats was strikingly suppressed as compared to that of the non-treated animals. Hexadimethrine bromide (HDM) was used to stain the anionic sites in the glomerular basement membrane. After injection of AN, the HDM-staining decreased chronologically, but the decrease was much less in the rats receiving the drug, corresponding with the suppression of albuminuria. The creatinine clearance did not fall so as to cause a decrease of albumnuria. It is suggested therefore that the anti-albuminuric effect of dilazep may be associated with preservation of the anionic sites in the glomerular basement membrane.

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