Intravenous sodium bicarbonate (NaHC03) infusion test was performed in 26 patients with chronic glomerulonephritis (CGN) and 16 with distal renal tubular acidosis (dRTA) in order to evaluate urinary acidifying capacity in chronic renal diseases. Comparative studies with glomerular filtration were planned, so that the patients with CGN were divided by creatinine clearance (Ccr) into 3 groups (G-I≥70, 30≤G-II<70, G-III<30 ml/min). Proximal tubular bicarbonate (HCO3) reabsorption rate increased in CGN as Ccr decreased. Urine to blood carbon dioxide tension gradient (U-B Pco2) was above 30 mmHg in controls and below 20 mmHg in dRTA. In patients with CGN, urine HCO3 concentration (UHco3) did not increase during NaHCO3 loading as Ccr decreased. How-ever, U-B Pco2 rose above 20 mmHg, when Uxco3 was above 50 ml/min. Fishberg concentrating test was also performed in 15 patients with CGN and 6 with dRTA so that the relationship between urinary concentrating ability and urine acidification might be evaluated. While both functions were decreased in dRTA, U-B Pco2 in alkaline urine remained above 20 mmHg in CGN associated with moderate renal dysfunction (Ccr≥30 ml/min) despite decreased maximal urine osmolality. Intravenous furosemide (FM) injection test was carried out in 8 patients with chronic renal failure (CRF) and 3 with dRTA. Minimal urine pH fell below 5.5 and net acid excretion (NAE) increased in controls, whereas these responses were not seen in dRTA. In CRF, urine pH generally decreased below 5.5 and those who had a similar response to FM as dRTA, seemed to have more severe disturbance of the distal acidification. In conclusion, U-B Pco2 in alkaline urine and lowered urine pH in FM loading appeared to be a useful index of distal tubular acid excretion in patients with renal dysfunction. In CGN with moderate renal dysfunction (Ccr≥30 ml/min), urinary acidi-fying capacity remained normal in comparison with decreased urine concentrating ability.

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We studied blood glutathione in children with idiopathic nephrotic syndrome (INS). Plasma glutathione concentrations were significatly (p<0.02) lower in INS patients at relapses (0.37±0.29 μg/ml, n=21) than those in controls (0.62±0.36 μg/ml, n=22). As compared with patients with chronic glomerulonephritis (316.4±128.3, n=8), the INS patients had lower blood glutathione concentrations (208.3±46.1 μ/ml, n=6), although the difference was not statistically significant (p<0.10). The glutathione, mixed in the solutions containing plasma proteins or bovine serum albumin, showed sequential reductions of the concentration with time. There was no significant difference between the blood glutathione concentrations in the rats given glutathione containing water for 7 days and in those given distilled water. An inverse correlation was noted between blood glutathione and plasma cholesterol levels in the rats. From these results it may be concluded that INS patients have a decreased blood glutahione level, although the cause is unknown.

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The kinetics of hemodialysis-induced leukopenia and generation of complement frag-ments including C3a, C5a, C4d, iC3b and Bb were investigated in 14 patients during hemodialysis using cellulose acetate (CA), cuprophan (Cu) and ethylenevinyl alcohol (EVA) membranes. A marked leukopenia in the first 15 minutes was observed in CA and Cu. Plasma C3a levels were higher in CA than in Cu and EVA. Plasma C5a levels were higher in CA and Cu than in EVA. There was a negative correlation between the white blood cell counts and plasma C5a levels at 15 minutes (γ=-0.85, p<0.001) . Plasma C4d levels showed no increase in all membranes. Plasma iC3b levels were higher significantly in Cu than in CA and EVA. Plasma Bb levels in the first 15 minutes increased significantly in all membranes, and furthermore continued to increase till the end of hemodialysis in CA and Cu. This study revealed that all the membranes tested activated the complement via the alternative pathway to produce Bb, iC3b, C3a and C5a. C5a was thought to take an important role in transient leukopenia. Furthermore, Bb was accumulated during hemodialysis in CA and Cu, and its biological effects on patients undergoing hemodialysis should be studied.

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The purpose of the present study was to compare hemodialysis (HD) and push/pull HDF in terms of uremic substance removal and clinical improvement. The treatment of patients complaining of shoulder joint pain was changed from conventional HD to HD or push/pull HDF using a hemodiafilter with larger membrane pores. Push/pull HDF showed significantly greater removal of β₂-microglobulin (β₂-m) and other small molecular pro-teins than HD, and serum β₂-m was significantly lower in concentration with push/pull HDF than HD. There was a decrease in the shoulder joint pain from push/pull HDF, and the range of upper arm movement thereby increased. However, neither this decrease in pain nor the increase in upper arm movement resulted with HD treatment. Hence, it was concluded that push/pull HDF is a more effective form of therapy.

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To determine whether pharmacological control of blood pressure could affect the renal function and its deterioration in SHR with renal ablation, we studied effects of oral administration of captopril (50 mg/kg/day) and ramipril (10 mg/kg/day), angiotensin con-verting enzyme inhibitors (ACEI), nilvadipine (10 mg/kg/day) and benidipine (3-6 mg/kg/day), calcium channel blockers (CCB), and indapamide (10 mg/kg/day), a non-thiazide diuretic, for 2 and 12 weeks on systolic blood pressure (SBP), blood urea nitrogen (BUN) and serum creatinine (Scr), endogeneous creatinine clearance (Ccr), and urinary protein excretion (UP) in SHR subjected to 5/6 nephrectomy a week before. Three weeks after the surgery, SBP (mmHg) in the untreated group was 253±8.9 (n=11), captopril group 156±8.9 (n=7, p<0.05), ramipril group 176±12 (n=7, p<0.05), nilvadipine group 146±8.8 (n=7, p<0.05), and benidipine group 197±8.5 (n=7, p<0.05). Monotherapy with indapamide (206±4.8, n=7, p<0.05) induced only a slight decrease in the SBP. Thirteen weeks after the surgery, SBP in the untreated group was 270±6.9 (n=14), in the captopril group 191±4.8 (n=7, p<0.05), in the ramipril group 160±9.5 (n=7, p< 0.05), in the nilvadipine group 177+13.2 (n=7, p<0.05), and in the benidipine group 150 ±4.9 (n=7, p<0.05). BUN was lower in the captopril and nilvadipine groups but not in the other treatment groups compared with the untreated group. Scr was lower in the ACEI groups. Ccr was higher in the ACEI and benidipine groups. UP was lower in all treatment groups. These results indicate that the similar reduction of SBP by ACEI and CCB has the potential to preserve renal function and to lessen renal damage in this model. Furthermore, they also suggest that ACEI have the potential to ameliorate renal function in this model. However, it remains to be determined why, despite the similar effects on SBP, deterioration of renal function in this model was prevented only by treatment with the ACEI, but not with the CCB.

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The purpose of the study was to determine the effect of dietary calcium intake on blood pressure and sodium ion transport of red blood cells (RBC) in spontaneously hypertensive rats (SHR). The SHR were fed by diet with three different levels of calcium contents as follows; 0.1% of Ca (low Ca diet), 0.6% of Ca (normal Ca diet) and 4.0% of Ca (high Ca diet) between 6 and 20 weeks of age. At 20 weeks of age, the levels of erythrocyte sodium efflux, as well as sodium and potassium contents in the RBC were measured. On the low calcium diet, SHR showed an enhancement of hypertension. On the high calcium diet, SHR showed an attenuation of the increase in blood pressure. In proportion to the levels of dietary calcium contents, SHR had a lower level of sodium contents in the RBC and a higher activity of the sodium pump. The passive sodium permeability and sodium-potassium cotransport in SHR were similar among low, normal and high calcium diet groups. It is concluded that the amounts of dietary calcium might be related to the regulation of blood pressure by changing the sodium pump of the cell membrane in SHR.

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We assessed the role of circulating digitalislike substance (s) on the blood pressure regulation in patients with essential hypertension, cardiac diseases, diabetes mellites and renal diseases by measuring digoxin-like immunoreactivity (DLI). Plasma DLI concentrations tended to correlate with blood pressure in all patient groups. Plasma DLI correlated to plasma aldosterone concentration in patients with essential hypertension, which suggested close interrelationship between DLI and electrolytes metabolism with adrenal steroids. Serum immunoreactive insulin (IRI) levels significantly correlated with blood pressure. Because plasma DLI levels correlated with serum IRI, increased levels of insulin could have induced sodium retention leading to increased DLI levels. Digitalislike substance, but not insulin, would have directly increased blood pressure in patients with abnormal glucose tolerance. Plasma DLI levels significantly correlated with the severity of renal insufficiency in patients with renal diseases. Plasma DLI highly correlated with amounts of plasma pro-teins, particularly with albumin, which would be due to the binding of DLI with albumin in plasma. Because the level of non-binding DLI is extremely low when assayed with a digoxin-radioimmunoassay, it was impossible to assess the level of a free-form of DLI, i.e., active DLI. That could be a reason why the correlation between the DLI and the other parameters was not highly significant. Collectively, these findings suggest that the DLI is one of the major determinants of blood pressure rises, regardless of any cause.

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We reported two cases of glomerulocystic kidney (GCK). Case 1 was a 35-day-old male who was born at 38 weeks of gestation and weighed 1750 g at birth, He showed chromosomal aberration and surface anomaly, and was dia-gnosed as having pentalogy of Fallot. There were no signs of renal disturbance. At autopsy, subcapsular cysts composed of dilated Bowman's capsules were found. Case 2 was a 63-year-old man. He suffered from mild cerebral infarction at the age of 45. At the age of 51, he was diagnosed as having chronic glomerulonephritis and began hemodialysis at the age of 55. He died of uremic lung at 63. Diffuse dilatation of Bowman's capsules were found in the renal cortices. In the liver, proliferation and cystic dilatation of interlobular bile ducts were noted. The patients with GCK without any severe disease in other organs show no or stable symptoms in the early period of life, but later developed severe renal insufficiency.

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During the 10 years from 1979 to 1988, 245 patients with urinary tract or prostate gland malignancy were diagnosed and treated at our Department. 245 malignancies were composed of 5 groups, i. e., 50 renal cell carcinomas (RCC), 17 renal pelvic and ureteral tumors (RPUT), 117 bladder tumors (BLT), 59 prostate carcinomas (PRC) and 2 urethral carcinomas (URC). On the basis of chief complaint or reason leading to diagnosis, and of grade of hematuria, evaluation was performed in 4 groups except for group URC. With regard to the chief complaint or reason leading to diagnosis, asymptomatic gross hematuria was most frequently seen at 40%, 59% and 74% in groups RCC, RPUT and BLT, respectively. In group PRC, asymptomatic gross hematuria was seen at 8%, although dysuria and urinary retention were the most popular. Regarding grade of hematuria at the first visit, urine without any RBC (55%) and microscopic hematuria (39%) were the commonest in group RCC, while moderate degree of microscopic hematuria (5-20/hpf) was most frequently seen in group RPUT (44%). On the contrary, gross hematuria (38%) was the commonest in group BLT. Patients in group PRC showed gross and microscopic hematuria at 25%, though it was not the com-monest one. In conclusion, it should be noted that no RBC may be seen on the first visit even if the chief complaint was gross hematuria in patients with urinary tract malignancy.

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The clinical picture, histopathological findings, therapy and prognosis of focal segmental glomerulosclerosis (FSGS) were investigated in a retrospective study involving 10 cases. The age of patient at the time of detection ranged from 3 to 19 years, 11 years on the average, being 9 years or above in 6 cases. There was noted a slight tendency toward predominance of males in this series. The disease was detected casually on the occasion of mass survey of urine at school in 6 cases (60%), while by clinical examination on visiting us with nephrotic syndrome in the other 4 (40%). Of the former 6 cases, 5 developed nephrotic syndrome while placed under medical surveillance. Nine of the 10 cases were treated mainly with corticosteroids, to which 5 (50%) were unresponsive and 4 (40%) responsive, with 1 (10%) of these 4 becoming unresponsive since a recurrence. Corticosteroids were not used in 1 case (10%). During follow-up period (which ranged from 1 to 10 years) 6 experienced an elevation of serum creatinine above 2.0 mg/dl, with 5 of them being unresponsive to corticosteroids and 3 begun on hemodialysis therapy. Histologically, cases in which the sum of the proportions of glomeruli affected with segmental sclerosis and with global sclerosis exceeded 30% and, in addition, there were severe tubulointerstitial lesions tended to have a poor prognosis, while those in which sclerosis involved less than 30% of glomeruli and no interstitial damage was discernible had a relatively favorable progonsis and were more frequently responsive to corticosteroids. These findings led us to conclude that FSGS has an ominous prognosis as reported previously and notably, the prognosis is much poorer for the non-steroid-responding type than for the responding type. The study also suggests that the degree of severity of histological changes is determinant of the prognosis of the disease.

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We report herein the case of a 14-year-old female who has acute tubulo-interstitial nephritis (AIN) associated with bilateral diffuse uveitis. She was admitted for the evaluation of "proteinuria", following general fatigue and weight loss about 2 weeks ago. Her laboratory data showed mild anemia, hyper γ-globulinemia, mild proteinuria, and the reduced glomerular filtration rate with the increased urinary excretion of β2-micro-globulin. The histological examination obtained by renal biopsy showed mild edema and diffuse infiltration of mononuclear cells in interstitium without any glomerular or vascular ab-normalities, which were compatible with AIN. As for the etiology of AIN, clinical investigations could not reveal any specific causes, such as bacterial and viral infections, drugs and systemic diseases, About 4 months after the onset of nephritis, she also became to suffer from bilateral diffuse uveitis. Therefore, the diagnosis of the acute tubulo-interstitial nephritis and uveitis syndrome (TINU sydrome) (Vanhaesebrouck et al., 1985) could be confirmed. In her clinical course, it was noteworthy that uveitis relapsed frequently in spite of systemic administration of prednisolone, and it took two years until uveitis cured, whereas the AIN subsided spontaneously prior to the specific treatment. In this case, characteristic fingings of granulomatous uveitis was closely similar to those of sarcoidosis, which has been rarely reported in TINU syndrome. In this respect, the involvement of immune processes, especially cell-mediated, was suggested as the pos-sible pathogenesis in this case.

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A 27-year-old man was admitted to our hospital for evaluation of renal function. Several months ago, renal dysfunction was discovered quite by chance. There was no family history of renal disease. On admission, the blood pressure was 140/82 mmHg. Laboratory examinations revealed hemoglobin of 14.4 g/dl ; BUN, 37.4 mg/dl ; serum creatinine, 2.3 mg/dl. The urinalysis showed specific gravity of 1.005, no proteinuria, no hematuria and no urinary sediment abnormalities. Creatinine clearance was 35 ml/min, and PSP test (15') showed 16%. An ultrasonographic study revealed atrophy of the right kidney and increased medul-lary echogenicity of the left kidney. A renogram showed non-functioning pattern of the right kidney and markedly impaired pattern of the left kidney. An open renal biopsy was performed on the left kidney. On light microscopy of the biopsy specimen, tubular dilatation, interstitial fibrosis, mononuclear cell infiltration and focal tubular atrophy were observed. No remarkable changes were found in the glomeruli. Electron microscopy revealed thickening of the tubular basement membranes (TBM). The clinicopathological findings of this case were compatible with nephronophthisis-cyctic renal medulla complex.

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We report a case of Alport syndrome. The patient, a nine-year-old boy, showed macroscopic hematuria after an upper respiratory infection seven years ago. Microscopic hematuria with proteinuria was pointed out in routine urinalysis at school. He had no apparent familial history of either progressive renal diseases or deafness. Renal biopsy was performed at the age of eight, and he was diagnosed as focal segmental glomerulone-phritis (mild) by light microscopy. Slight irregular thickening of the glomerular basement membrane (GBM) was observed focally by electron microscopy. Both light microscopy and electron microscopic examinations did not indicate a hereditary nephritis. The 28-kilodalton (kDa) monomers of the non-collagenous globular domain (NC-1) of type IV collagen were abscent along renal glomerular capillary walls from the patient by indirect immunoflorecence while they were normally observed in glomerular capillary walls from healthy subjects and patients with a variety of non-hereditary glomerulonephritis. It was suggested that immunofluorecence using a monoclonal antibody for the NC-1 domain of type IV collagen is useful in the precise diagnosis of the patients with Alport syndrome.

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This case was a 51-year-old woman, who had been diagnosed as having rheumatoid arthritis at some clinic and had been treated with both non-steroidal anti-inflammatory drugs and steroid 3 years before visiting our clinic. When she noticed a decrease in visual acuity and general fatigue in June 1985, she was referred to an ophthalmologist of our hospital, and found to have blood pressure of 240/150 mmHg and KW grade IV retinal findings. She was admitted in our department to examine and treat malignant hypertension. On admission, remarkable hypergammagloburinemia (29.3%), arthralgia, arthral deformity and pericardial effusion were present thus, she was suspected to be suffering from malignant rheumatoid arthritis. Anti-nuclear antibody (64 ×), anti nuclear ribonucleo-protein antibody (64×) and anti-RNase sensitive antibody of anti-extractable nuclear antigens (ENA) antibody (81920×) were positive, while anti-RNase resistant antibody of anti-ENA antibody was negative. Immunologically, her condition was consistent with mixed connective tissue disease (MCTD). Since urinary protein was positive and creatinine clearance was 46.0 ml/min, renal function was thought to be diminished. Her chest roentgenogram revealed cardiomegaly (CTR 67.5%) and an increase in pulmonary vascular shadow. An echocardiogram demonstrated the presence of pericardial effusion. Plasma renin activity was 3.3 ng/ml/h and it was suspected that an intrarenal ischemic change resulted in increased renin release from the juxta-glomerular apparatus, leading to the marked hypertension. Treatment was started with predonisolon 60 mg/day during 4 weeks. Prazosin and captopril were also given and effective to decrease blood pressure to 140-160/90-100 mmHg. Predonisolon was gradually reduced to 30 mg/day with disappearance of the pericardial effusion and improvement of her immunological data and symptoms. Creatinine clearance was improved to 73.2 ml/min. Anti-ENA antibody de-creased to 2560 ×. It is suggested that her malignant hypertension was induced by some intrarenal vascular change probably caused by MCTD, and that steroid therapy was effective to improve her general condition.

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