Biochemical, light and electron microscopic, and cytochemical studies were made of the proximal tubules in the kidney of adenine-ingesting rats fed on a 0.75% adenine diet for 1 to 4 days. Histologically, acicular crystals appeared in the proximal tubules on the 1st day and increased in number and size day by day. The alkaline-phosphatase (Al-Pase) activity in the kidney was increased on the 1st day and decreased after the 2nd day, but the serum Al-Pase activity remained stationary during the experiment. On the other hand, the acid-phosphatase (Ac-Pase) activity showed no variation in both the kidney and serum. Elec-tron microscopy revealed that 2, 8-dihydroxyadenine (DHOA) crystals were precipitated in the microvilli and apical region of the proximal tubular epithelia, and increased crystals were accompanied by degenerative changes in the cells of these tissues. Cytochemically, Al-Pase activity was observed in the microvilli of the proximal tubular epithelia and diminished according to loss of the microvilli caused by the formation of DHOA crystals. Ac-Pase was well preserved in the lysosomes of the proximal tubular epithelial even when DHOA crystals had grown so as to occlude the tubular lumina.

抄録全体を表示

Nephrotic syndrome (NS) is a relatively unusual finding in patients with IgA nephropathy. In a retrospective study of 164 adults with IgA nephropathy over the past 8 years, we encountered 17 patients (8 males, 9 females) which presented with NS at their onset or during their clinical course. Among those who had massive proteinuria, a decrease in creatinine clearance (less than 70 ml/min) was recognized in 12 patients, an elevation of serum IgA (more than 400mg/100ml) in 8 patients, and hypertension (greater than 160/95 mmHg) in 5 patients. Most of the renal histopathological pictures revealed findings of glomerular hyalinosis and/or sclerosis and crescent formation indicative of a poor prognosis. Corticosteroid therapy which was given to 15 patients was ineffective in 4 patients, of which 3 patients required artificial dialysis. Eight patients achieved complete remission of NS which was followed by frequent relapses. It can thus be concluded that many patients with IgA nephropathy associated with NS have a generally poor prognosis in correlation with histological glomerular damage. Nevertheless, some patients are similar to minimal change nephrosis as frequent relapsers, which constitute a variant of IgA nephropathy or minimal change nephrosis.

抄録全体を表示

Eight patients with nephrotic syndrome showing glomerular IgA deposits who were strongly steroid-responsive and multiple frequent relapsing, are described. In general, nephrotic syndrome or nephrotic range proteinuria in IgA nephropathy has been identified as one of the possible indicators of a poor prognosis. However, the findings in all of our 8 patients, who were very similar but not equal to classical minimal change nephrosis in their clinical courses and histopathological findings, suggest the possibility of a variant of IgA nephropathy or minimal change nephrosis.

抄録全体を表示

Plasma volume (PV), plasma renin activity (PRA), plasma aldosterone (PA) and urinary sodium excretion were examined in 17 nephrotic patients showing chronic glomerulonephritis (GN) with normal renal function, and the results were compared with those of 17 nephrotics with minimal gomerular lesions (MC), either at the edema forming stage or at the edema sustaining stage. PV in GN was below normal irrespective of the stage. However, PV in MC was lower than that in GN and the difference was statistically significant at the edema forming stage. Among all the cases, a slight but significant inverse correlation was noted between PRA and PV. Significant positive correlations were also observed between PRA and PA, and between PA and urinary sodium excretion. The renin-angiotensin-aldosterone system appears to be affected secondarily by the changes in PV. It is concluded that PV at the edema forming stage is diminished in GN nephrotics with normal renal function as well as in MC nephrotics.

抄録全体を表示

In order to examine the mechanism of fluid retention in idiopathic edema, we studied the changes in plasma volume, hormones (renin, prolactin and aldosterone) and urinary sodium and free water in response to water ingestion, in the upright position. The effect of the dopamine agonist, bromocriptine, on these parameters was also investigated. The plasma volume was estimated from the distribution of 131I-albumin, and the plasma hormone concentration was measured by radioimmunoassay. Studies were performed on 4 normal controls and 9 patients with idiopathic edema. In the normal controls, water ingestion caused an increase in plasma volume and urinary excretion of free water and sodium. In 4 of the patients with idiopathic edema (group A), water ingestion induced a reduction in plasma volume, a normal response in the free water excretion and a diminished response in the urinary sodium excretion. In the other 5 patients (group B), water ingestion led to normal responses in the plasma volume and urinary sodium excretion, but a diminished response in the free water excretion. Exaggerated responses of the hormone secretions following water ingestion were found in all patients. Administration of bromocriptine for 5 days sup-pressed the aldosterone and prolactin levels in all patients. It did not affect the other parameters studied in the group B patients, but ameliorated the abnormal responses of the plasma volume and urinary sodium excretion in the group A patients. These results suggest that patients with idiopathic edema may consist of heterogeneous groups. In one type of patients (group A), idiopathic edema may be associated with altered regulation of plasma volume and urinary sodium excretion. In the other type (group B), idiopathic edema may be associated with altered regulation of free water excretion. The findings also indicate a possible pathogenic role for the dopaminergic system in the former group, but not in the latter.

抄録全体を表示

The effects of hydrostatic pressure in the renal excretory system on adenine nucleotides and inorganic phosphate were investigated in human hydronephrotic kidneys. Specimens were obtained surgically. Measurements of adenine nucleotides were performed according to the method of Hurlbert and Potter. From the results, Atkinson's energy charge was calculated. Martin-Doily's method was employed to measure the inorganic phosphate in the hydronephrotic kidneys. Surgically obtained specimens were incubated in vitro with radioactive phosphate tracer to investigate the turnover of phosphate. The degree of hydronephrosis was determined according to Oka's criteria. The results showed that the levels of renal tissue adenine nucleotide (ATP) in degree C and D hydronephrosis were decreased to 70% and 60% of normal, respectively. The inorganic phosphate contents also fell. However, there were no great differences in energy charge between C and D hydronephrosis, and no significant differences between these groups and the control. The turnover rates of radioactive phosphate in adenine nucleotides and inorganic phosphate revealed a marked decrease.

抄録全体を表示

The effects of captopril, an angiotensin converting enzyme inhibitor, and nicardipine, a calcium channel blocker, on kidney weight and creatinine clearance (Ccr) were examined in the early stage of diabetes in unilaterally nephrectomized rats. Wistar rats were subjected to unilateral nephrectomy before injection of streptozotocin. One week later, increases were observed in urine volume from 10±0.8 to 160±5ml/day, and in the urinary excretions of glucose from 1.1±0.1 to 11681±363mg/day, N-acetyl-β-D-glucosaminidase (NAG) from 14.0±2.2 to 202±6 nmol/min/day and protein from 21, 4±1.7 to 51.9±3.5 mg/day, concomitant with substantially high levels of blood glucose (477±18mg/dl). In addition to significant increments in kidney weight from 0.53±0.02 to 0.90±0.03 g/100g body weight and Ccr from 13.3±1.5 to 18.8±1.0 dl/day, blood pressure was also higher in the diabetic rats (control 119±10, diabetics 127.3±3 mmHg). Administration of captopril for one week significantly attenuated this hyperfiltration to 16.6±0.8 dl/day and reduced the weight of the kidney to 0.77±0.03g/100g body weight. Although nicardipine prevented the diabetes-related increment in renal mass (0.74±0.03g/100g body weight), it had no effect on the hyperfiltration (19.1±1.4 dl/day). Captopril significantly lowered the blood pressure from 127±3 to 117±2 mmHg and nicardipine lowered it from 127±3 to 122±1 mmHg in the diabetic rats, but neither compound affected the urinary excretions of protein and NAG. Thus, captopril and nicar-dipine appeared to inhibit the increment of renal growth in diabetic rats.

抄録全体を表示

Exaggerated natriuresis in SHR with acute saline infusion was accompanied by increased neuronal activity in the NTS, which was mediated through vagal afferents. The inhibitory effect of the NTS on the renal sympathetic nerve activity appeared to function as well as in WKY.

抄録全体を表示

A patient showed nephrotic syndrome at 1 year and 7 months after the onset of Weber-Christian disease. She died at the age of 42 years old and the total clinical course was about 8 years. At autopsy, immune complex glomerulonephritis, chronic active hepatitis with vasculitis and chronic thyroidits (Hashimoto) were found. To our knowledge, this is the first case of Weber-Christian disease complicated with various diseases associated with abnormal immune mechanism, not concomitantly. This case rein-forces the view that an autoimmune mechanism may be involved in the pathogenesis of Weber-Christian disease.

抄録全体を表示

The influence of climatic factors on the incidence of urinary stone colic was studied. The investigation was conducted over a three-year period and involved 433 patients resident in Tokyo. Humidity, rainfall and windspeed showed no correlation with the incidence of colic. However, changes in atmospheric pressure revealed a significant relationship with colic, a fall in pressure increasing its incidence and rise in pressure decreasing it. Although colic occurred frequently in the summer, no relationship was observed between temperature and the precipitation of colic after adjustment for seasonal variations. Changes of temperature, however, strongly influenced its occurrence. A rising temperature on hot days with a mean temperature of over 20°C was associated with a high incidence. Although a fall in temperature on cold days revealed a tendency to increase colic, the effect was not significant in Tokyo where days with a mean temperature of under 0°C are rare.

抄録全体を表示

In order to clarify the pathophysiological roles of renal thromboxane (TX) A₂ in protein excretion and renin release, the urinary excretion and renal synthesis of TXB₂ were assessed in rats with streptozotocin-induced diabetes. Four weeks after the onset of diabetes, marked proteinuria and hyporeninemia were observed together with an approximately 4-fold increase in TXB₂ excretion. However, the renal TXA₂ synthesis was lower than in pre-diabetic controls. Although daily administration of the selective TXA₂ synthesis inhibitor, OKY-046, at 10mg/kg i.p. for 4 weeks after the onset of diabetes did not affect the TXA₂ synthesis and excretion, the urinary excretion of prostaglandin (PG) E₂ and 6-keto-PGF1 y tended to be augmented in association with normalization of the decreased plasma renin activity (PRA), possibly through increased renal renin release. On the other hand, OKY-046 at 100mg/kg i.p, did suppress the renal TXA₂ synthesis together with the urinary excretion of other eicosanoids. The PRA and cortical renin release were again significantly augmented. Microalbuminuria observed in the 4-week diabetic rats tended to decrease upon TXA₂ synthesis blockade. Urinary TXB₂ excretion was positively correlated with proteinuria or albuminuria. However, inhibition of TXA₂ synthesis which was initiated at 4 weeks after the onset of diabetes did not attenuate the proteinuria. These results suggest that renal TXA₂ may be linked with renin release, through either a direct inhibitory action or preserved renal functions upon TXA₂ synthesis blockade, and that it may represent one of the factors responsible for increasing proteinuria, although augmented urinary excretion of TXB₂ may be derived from platelet-borne TXA₂.

抄録全体を表示