The existence of podocalyxin (PCX) in urine sediments of 30 children with IgA nephropathy was identified by positive findings of immunofluorescence testing using a monoclonal antibody (PHM-5 ). Three structures (cells (podocytes), casts, granules) were stained and arbitrarily scored according to their numbers and intensity of fluorescence. The urinary scores for podocytes and casts were higher in the acute stage than in the chronic stage (p>0.02 and p>0.01, respectively). Protein excretion and hematuria showed a strong parallel correlation in the podocytes (p>0.005 and p>0.001), and in the casts (p>0.001 and p>0.005) in the urine sediments. The urinary scores for podocytes and casts were significantly higher in cases with extracapillary lesions (p>0.003 and p>0.01) and with interstitial lesions (p>0.02 and p>0.008) but no correlation existed with the intensity of mesangial proliferation. The urinary scores for podocytes and casts were also higher in cases with mesangiocapillary IgA deposits (p>0.04 and p>0.04) and C 3 deposits (p>0.03 and p>0.04). These findings suggest that PCX in the urine sediments indicate the degree of the glomerular epithelial cell injury and is useful for clinical evaluations.

抄録全体を表示

Lipid metabolism in chylomicron and VLDL were examined in daunomycin-induced nephrotic rats. 1 ) There was no difference in intestinal cholesterogenesis between the control rats and daunomycin-induced nephrotic rats. 2 ) The apoprotein content of chylomicron and VLDL increased in daunomycin-induced nephrotic rats. 3 ) Daunomycin-induced nephrotic rats showed increases in the content of apo B-48 and C-III, and a decrease in that of apo E in chylomicron . The apoprotein composition of VLDL in daunomycin-induced nephrotic rats showed increased apo B and decreased apo E. These results suggest that increased chylomicron-cholesterol is not due to increased intestinal cholesterogenesis, but to decreased chylomicron catabolism in daunomycin-induced nephrotic rats. Increased apoprotein in VLDL may contribute to the decreased catabolism by reducing LPL activity in the plasma and increased secretion from the liver of daunomycin induced nephrotic rats.

抄録全体を表示

In order to clarify the antinephritic mechanisms of Sairei-to (TJ-114), the effects of TJ-114 on the expression of adhesion molecules were evaluated in rats with anti-GBM nephritis. TJ-114 was administered orally once a day from the day (1st day) after anti-GBM serum injection throughout the experiment. TJ-114 inhibited crescent formation in glomeruli at the 10th day compared to control rats with anti-GBM nephritis. The ICAM-1-or VCAM-1-positive area in the glomeruli was increased in the nephritic control rats at the 10th day. In contrast, TJ-114 prevented increase in the ICAM-1-or VCAM-1-positive area in the glomeruli of nephritic rats. TJ-114 inhibited increase in the number of LFA-1-or VLA-4-positive cells in the glomeruli. One of the constituent components of TJ-114, Syo-saiko-to (TJ-9) at the dose of 750 mg/kg, also significantly inhibited increase in the ICAM-1-or VCAM-1-positive area in the glomeruli. Gorei-san (TJ-17), another component of TJ-114, inhibited increase in the ELAM-1-positive area and increase in the number of VLA-4-positive cells in the glomeruli. Prednisolone markedly inhibited increase in the positive area of those adhesion molecules and increase in the number of ligand-molecule-positive cells in the glomeruli. These results indicate that the antinephritic action of TJ-114 may be partially due to inhibition of adhesion molecule expression in the glomeruli.

抄録全体を表示

To assess the role of insulin resistence in the hypotensive effect of weight loss, insulin sensitivity was examined by the euglcemic insulin clamp method in 15 untreated obese hypertensive patients with a body mass index of 25 kg/ m2 or greater (4 men and 11 women, with a mean age of 53.4 years) before and 4 weeks after being placed on a low-calorie diet of 800 Cal/ day with mild exercise. Body weight decreased by 11.0% (from 74.3±3.8 to 66.1 plusmn;3.0 kg; p<0.01) with a concomitant fall of mean blood pressure from 122.5±2.3 to 108.6plusmn;2.4 mmHg (p<0.01). Glucose infusion rate (GIR), as an index of insulin sensitivity, was significantly increased by 54.3% (from 3.66 ± 2.4 to 5.5 ± 9.3 ml/ kg/ mm.; p<0.01). Plasma levels of fasting blood sugar and insulin decreased significantly by 11.8% and 58.4%, respectively (both p<0.01). The change in mean blood pressure showed a negative correlation with the change in GIR resulting from weight loss (r=-0.79, p<0.05). These findings suggest that the hypotensive effect of weight loss in hypertensive patients with obesity is partly related to improvement of insulin sesitivity.

抄録全体を表示

Clinicopathological features and prognosis were studied in 291 Japanese patients (4 to 60 years of age) with IgA nephropathy to investigate the influence of age on this disease. Histological assessment was done using the semiquantitative scoring system consisting of the activity index (Al) and chronicity index (Cl). 1) Cl scores, especially global glomerulosclerosis and tubulointerstitial change, markedly increased with age, while Al scores slightly increased. 2) The Cl scores and rate of chronic renal failure (CRF) increased, especially in patients beyond 30 years of age. 3) A higher rate of CRF or regular hemodialysis was found in patients with Cl ≥4 compared to those with Cl > 4 (211%, 2.9% respectively). These results suggest that chronic, irreversible histologic changes increase with age, especially beyond the age of 30 years, which worsens the prognosis of patients with IgA nephropathy.

抄録全体を表示

Serum concentration of the pyridinium cross-links, pyridinoline (Pyr) and deoxypyridinoline (Dpyr), which are markers of bone resorption, was measured by high-perfomance liquid chromatography in 56 patients on maintenance hemodialysis. The following analyses were conducted: 1) correla-tion with known markers of bone metabolism, 2 ) correlation with findings on bone changes on plain X-ray film, 3 ) elimination rates by hemodialysis, and 4 ) increment per day in pyridinoline after hemodialysis ( Δ Pyr/ day) . There was a very close correlation found between serum Pyr and Dpyr (r =0.861). Both serum Pyr and Dpyr showed correlations with known markers of bone metabolism: C-PTH (r =0.806 and r =0.747, respectively), M-PTH (r =0.766 and r =0.749), osteocalcin (r =0.717 and r =0.693), Alp-3 (r =0.523 and r =0.441) and tartrateresistant acid phosphatase (r =0.549 and r = 0.548). In addition, a correlation between the duration of hemodialysis and serum Pyr and Dpyr was observed (r =0.426 and r =0.318, respectively). When comparing the mean values of serum Pyr or Dpyr in three groups of patients divided according to bone changes seen on plain X-ray film, there were statistically significant differences between the group without bone changes and the remaining two groups with some bone changes (p<0.05) . A mean of 45.3 % of serum Pyr was removed by hemodialysis. The serum Pyr level returned alomst to the original concentration by the following hemodialysis. ΔPyr/ day showed a close correlation with C-PTH (r = 0.656). There was a very close correlation between serum Pyr and ΔPyr/ day (r = 0.830). These results indicate that serum Pyr and Dpyr are useful parameters of renal osteodystrophy. However, samplings should be made under uniform conditions.

抄録全体を表示

A male patient with hyperplasia of the juxtaglomerular apparatus, hypokalemia, an associated increase in plasma renin activity and hyperaldosteronism without hypertension was diagnosed as having Bartter's syndrome at the age of three. He was treated with spironolactone, indomethacin and potassium supplements. However hypokalemia, increased plasma renin activity and hyperaldoste ronism persisted. Proteinuria was observed at the age of fifteen. Because of the gradual reduction of his renal function, the patient was admitted to our hospital and underwent hemodialysis at the age of twenty-one. He was normotensive. Serum potassium was within the normal range . Plasma renin activity and aldosterone concentration levels were still elevated. Renal biopsies, which had been carried out four times throughout his treatment, revealed an increase in sclerosis of the glomerular mesangial region, and interstitial fibrosis in proportion to narrowing of the small arteries in association with the juxtaglomerular hyperplasia. These findings suggested that changes in the glomeruli and interstitium of the kidney were secondary to long-standing hypokalemia, stenosis of the small arteries and the effects of the prescribed drugs for Bartter's syndrome.

抄録全体を表示

The management and screening of unruptured asymptomatic intracranial aneurysm (ICA) in patients with ADPKD and those with a family history of ICA remains a subject of considerable controversy. In recent years, it has been revealed that MRA (magnetic resonance angiography) can define the circle of Willis to allow detection of ICA as small as 3-4 mm. We report a case of a 63-year-old man with ADPKD and his family. No definite aneurysm was observed by angiography screening at 46 years of age, when he was referred for hemodialysis. For the past three years, his family history revealed that three relatives were suffering from subarachnoid hemorrhage at the ages of 32, 36 and 39 years, respectively, two of whom had ICA and one had arterio-venous malfomation detected by angiography. Whether they had ADPKD was unknown, but two were suggestive of ADPKD. Therefore, our case underwent MRA as screening for ICA, which showed an ICA with a diameter of 5mm in the anterior communicating artery. The ICA was confirmed as being 6 mm in diameter by conventional angiography. His niece and her son, who had ADPKD, also underwent MRA, which showed a suspicious image of a 2 mm ICA in the latter case. These results suggest that prophylactic screening for ICA is important in an ICA clustering family. MRA is useful in screening for ICA and in the follow-up study on the natural course of ICA.

抄録全体を表示