Since insulin resistance and/or hyperinsulinemia may contribute to structural changes of the vascular wall, the influence of antihypertensive agents on insulin sensitivity could interfere with the long term outcome of blood pressure reduction. Although it is postulated that increased peripheral circulation due to vasodilating agents improves insulin sensitivity, reflex sympathetic activation elicited by blood pressure reduction may influence insulin sensitivity. Thus we investigated the different effects of an alpha blocker (doxazosin) as well as a direct vasodilation (hydralazine) on insulin sensitivity and on sympathetic function in spontaneously hypertensive rats (SHR). Doxazosin and hydralazine decreased mean arterial pressure to a similar extent. Doxazosin, but not hydralazine decreased steady state blood glucose. Plasma norepinephrine increased in doxazosin and hydralazine treated groups as compared to the control group. Thus, despite their similar effects on blood pressure and plasma norepinephrine, alpha -1 blocker improved insulin sensitivity while the direct vasodilator failed to do so, and this difference is probably related to blockade of the alpha-1 receptor rather than to peripheral vasodilation.

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The exfoliation and decrease is peritoneal mesothelial cells and the presence of interstitium hyperplasia are often observed in peritoneal membrane dysfunction caused by long-term peritoneal dialysis. The suppression of peritoneal mesothelial cell proliferation may be the cause of these phenomena. The objective of this study is to clarify the mechanism by which highly concentrated glucose of peritoneal dialysis fluid inhibits mesothelial cell proliferation. We examined the effect of highly concentrated glucose in the medium on human peritoneal mesothelial cell proliferation and TGF-β₁ mRNA expression. The effect of Ham's F12 media containing various levels of glucose concentration was compared with that of normal medium. We investigated human peritoneal mesothelial cell proliferation by [3H] thymidine incorporation assay and TGF-β₁mRNA expression on human mesothelial cells by the RT-PCR method. The suppression effect of glucose and TGF-β₁ on human peritoneal mesothelial cell proliferation was dose-dependent (glucose ; 0-5 %, TGF-β₁, ; 0-1000 pg/ml). TGF-β₁ mRNA of cells in 4% glucose medium was greater than that in the control medium. The glucose-induced suppression of human peritoneal mesothelial cell proliferation was relieved by LAP and TGF-β neutralizing antibody. In conclusion, TGF-β₁ may play a critical role in inhibiting mesothelial cell proliferation in media with highly concentrated glucose.

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The aim of this study was to evaluate the influence of LCD on bone metabolism, and assess the indication of LCD. Fourteen patients on CAPD(m=8, f=6) were converted to LCD following over 1 year on standard calcium dialysate (1.75 mmol/l ; SCD) treatment, and followed for 1 year. The biochemical measurements included plasma levels of Ca, P, ALP, and i-PTH. The bone mineral density (BMD) was evaluated using dual energy x-ray absorptiometry. Ca-carbonate and calcitriol were administered to maintain plasma Ca levels within the normal range. The patients were divided into three groups on the basis of the i-PTH levels just before the conversion to LCD. Group 1;n= 5, i-PTH<65.Group 2;n=5, 65≤ i-PTH<200. Group 3;n=4, 200≤ i-PTH (pg/ml). Mean BMD Z scores decreased significantly in group 3. Mean serum i-PTH significantly increased in all groups. These results suggest that LCD is effective for treating adynamic bone disease, which is seen in high frequency in patients undergoing peritoneal dialysis. However, these results also pointed to the disadvantage of worsening the secondary hyperparathyroidism. In conclusion, LCD should be used carefully in patients whose i-PTH levels are high, because of the possibility of bone mineral loss.

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Seven patients undergoing chronic hemodialysis three times a week and whose plasma bicarbonate concentration on predialysis was consistently under 18 mmol/l due to bicarbonate dialysis (BCD), were treated with BCD for 2 weeks, then switched to acetate-free biofiltration (AFB) for 8 weeks. In both periods, the same high flux dialyzer (AN69HF) was used. The treatment time, dialysate flow rate and blood flow rate were kept constant in each patient during both periods. Plasma bicarbonate concentration (HCO^-₃), serum urea nitrogen (SUN), serum creatinine (Cr) and plasma amino acids concentrations (AA) were measured before dialysis and KT/V was calculated on the 2nd days of the last week in both periods. HCO^-₃ on AFB was significantly higher than that on BCD (16.4±0.9 vs 19.9±1.8 mmol/l ; p<0.05). SUN on AFB was significantly lower than that on BCD even though the dialysis schedule and dietary content were not changed (84.7±3.7 vs 76.6±3.8 mg/dl;p < 0.05). TP, Cr and KT/V were not significantly different. Plasma total amino acid concentration (TAA) and plasma essential amino acid concentration (EAA) were not significantly different in both periods. In contrast, plasma branched-chain amino acid concentrations (BCAA) on AFB were significantly higher than that on BCD ( 313.5±44.3 vs 390.3±50.7 μmol/l; p <0.05). Plasma BCAA concentrations, valine (VAL), leucine (LEU) and isoleucine (ILE), were significantly higher on AFB than that on BCD, respectively (p <0.05). These findings suggest that optimal correction of the metabolic acidosis in chronic hemodialysis patients by AFB leads to a significant increase in plasma BCAA concentration.

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It has been reported that circumferential mesangial interposition (CMI) is an important mor phological feature suggesting the progression of glomerulosclerosis in glomerular disease. The relation between CMI and its associated lesions was investigated in various renal diseases by electron microscopy. In 276 patients, of whom the glomeruli were observed by electron microscopy, CMI was observed non-specifically in 48 patients with various glomerular diseases (IgA nephropathy, 11; non-IgA glomerulone phritis, 1 ; membranoproliferative glomerulonephritis, 8;membranous nephropathy, 5;lupus glomer ulonephritis, 12;toxemia of pregnancy, 2;diabetic nephropathy, 7;mitomycin nephropathy, 1;and Seckel's dwarfism patients, 1). The glomeruli with CMI showed a marked increase in mesangial matrix, as well as various grades of mesangial cell proliferation. Mesangiolysis associated with subendothelial widening was observed in a lesion of CMI in most cases . This phenomenon appears to be an initial alteration that conducts proliferated cells to the peripheral portion of a capillary loop. Localized severe thinning of the glomerular basement membrane was frequently combined with CMI, particularly in IgA nephropathy patients. Endothelial cells were occasionally interposed into the widened subendothelial space . Subendothelial deposits were noticed in the CMI lesion, particularly in MPGN patients. In conclusion, in the process of glomerulosclerosis progression in various glomerular diseases, lytic and edematous changes initially occur in the mesangao-subendothelial system (mesangiolysis and suben dothelial widening), then proliferating mesangial cells extend into the widened space (between GBM and endothelial cells), and reach the peripheral portion of a capillary loop.

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Renal amyloidosis shows symptoms of renal dysfunction due to the deposition of amyloid protein in the kidney. Recently, it was reported that apoptosis plays an important role in the pathogenesis of type 2 diabetes mellitus and Alzheimer's disease of which amyloid deposition is seen in the tissue. We investigated whether or not apoptosis and related factors are observed in renal amyloidosis. In situnick end labeling (TUNEL) was performed in seven autopsied renal tissues with primary and secondary amyloidosis and 10 autopsied renal tissues without renal disease as the control. The number of TUNEL - positive cells was significantly increased in both the glomeruli and tubulus of the kidney with amyloidosis than in the control. Electron microscopic analysis was performed on one biopsied renal tissue with amyloidosis and six biopsied renal tissues with minor abnormalities as the control. Typical apoptotic cells were observed only in the former. Bax product, an inducer of apoptosis, and Bcl-2 protein, an inhibitor of apoptosis, were examined immunohistochemically in the seven autopsied renal tissues with amyloidosis and 10 autopsied control tissues. Bax was overexpressed in the tubulus and glomeruli of subjects with renal amyloidosis, compared to the normal controls. However, Bcl-2 protein was not detected in the glomeruli in any of the subjects examined. These results indicate that apoptotic cells are increased in number in renal amyloidosis and Bax overexpression may play an important role in this increase.

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Although systemic AA amyloidosis complicating Crohn's disease has been found in 0.5 to 6 % in America and Europe, it is relatively rare in Japan. We report a case of systemic AA amyloidosiscomplicating Crohn's disease. In 1979, a 26-year-old Japanese man presented with diarrhea, melena andperianal abscesses, and was diagnosed as having Crohn's disease. He was treated with oral prednisolone, salazosulfapyridine and diet therapy. However, the gastrointestinal symptoms recurred and he was hospitalized several times. In his thyroid gland was found to be swollen, but with normal thyroid function, and his thyroid gland became larger subsequently. In he showed renal dysfunction (blood urea nitrogen 33.2 mg/dl ; serum creatinine 1.5 mg/dl) with proteinuria. His renal function had been deteriorating rapidly. On 1996, he was admitted to At the time of admission, his renal function showed a blood urea nitrogen of 129.5 mg/dl with a creatinine of 5.4 mg/dl. The urine contained 0.8 g of protein per 24 hours. He presented with diarrhea for several days before admission and was treated with central venous hyperalimentation. Despite supportive care, he developed end-stage renal failure, then hemodialysis was initiated on His condition was complicated by a complete auriculoventricular block on He died of hemoperitoneum on On postmortem examination, extensive amyloid deposits were found in multiple organs including kidneys, intestine, heart, thyroid gland, lungs, liver, spleen, pancreas, gall bladder, adrenal glands, testis, prostate, bone marrow and parathyroid glands. Analysis of amyloid protein in the autopsy specimens showed type AA.

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We report a 50-year-old male patient with hepatitis C virus (HCV)-associated membranous glomer ulonephritis (MN), for which he had been treated with corticosteroid therapy for one and a half years. This patient received blood infusion at 38 years of age. He visited our hospital because of liver dysfunction at 42 years. One year later, proteinuria and microhematuria were pointed out (43 years). Renal biopsy revealed MN with focal fibrocellular crescents. HBsAg, cryoglobulin, rheumatoid factor were all negative. Prednisolone was administered at the dose of 30 mg/day for 4 weeks and tapered subsequently. The steroid treatment was effective (urinary protein excretion: 4.2→0.3 g/day, serum albumin: 2.4→4.0 g/dl, 3 months later), and transaminase slightly elevated (GPT 50→60-80 IU/l). One and a half years later he proved to be positive for HCV antibody, and corticosteroid administration was terminated. Subsequently proteinuria increased, and reached 3.0 g/day 6 years later. However, serological markers and ultrasonographic study for chronic hepatitis revealed mild changes of the liver. These findings suggest that corticosteroid therapy is not contraindicated against HCV-associated MN, and may possibly be used as the treatment for this condition.

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A 47-year-old woman was admitted to our hospital for evaluation of general fatigue and dyspnea. She had been diagnosed with progressive systemic sclerosis (PSS) when she was 39 years of age, on the basis of Raynaud's phenomenon, proximal sclerosis, and pigmentation of the skin. On admission, her blood pressure was 206/128 mmHg. Funduscopy revealed grade III (Keith & Wagener) hypertensive retinopathy. Laboratory data showed positivity for anti-nuclear antibody and anticardiolipin β₂ glycoprotein I antibody, and the plasma level of renin activity (PRA) was abnormally high. Chest X-ray and UCG revealed massive pericardial effusion. On the second hospital day, she was operated on for pericardio diaphragmatic fenestration. The volume of pericardial effusion amounted to more than 2000ml. Postoperative malignant hypertension persisted. Laboratory data showed thrombocytopenia, hemolytic anemia, and acute renal failure. We diagnosed scleroderma renal crisis (SRC) associated with antiphos pholipid syndrome. Following the initiation of angiotensin converting enzyme inhibitor (ACE-I) com bined with calcium antagonisit and alpha-one blocker, her blood pressure and PRA decreased. She also had been treated with aspirin 81 mg daily. These therapies were effective in recovering the platelet count and stopped the progression of anemia and renal failure. Although either the finding of large pericardial effusion or SRC is associated with poor prognosis in PSS, this case has had a good clinical course. In this case, the findings suggested that anti-phospholipid antibody may have contributed to the pericarditis and SRC.

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We report a case of a 65-year-old man presenting with multicentric Castleman's disease (MCD) accompanied by membranoproliferative glomerulonephritis-like lesion with fibrillary deposits. The lesion was characterized by highly organized ultrastructual deposits that were negative for Congo-red stain and for immunoglobulin, light chain and C₃. Thus, this renal lesion was considered histologically to be fibrillary glomerulonephritis presenting by light microscopy as mesangiocapillary glomerulonephritis. To our knowledge, among the limited number of cases of renal lesion associated with MCD ever reported, this is the first case of a biopsy-proven fibrillary glomerulonephritis. Serum interleukin 6 (IL-6), known as an indicator of MCD activity and as an autocrine growth factor for mesangial cells, was chronologically measured. Augmentation of urinary IL-6 simultaneously with that of extra renal symptoms of MCD and associated renal disease may indicate an underlying role of this cytokine in the present case. Failure to detect of IL-6 in the glomeruli may support the notion that IL-6 is derived from extrarenal lymphonodi, and not to an in situ product of the glomeruli. However, it may have been related to glomerular injury .

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We report a case of 45-year-old woman with Bartter's syndrome and concomitant renal dysfunction . In the patient demonstrated muscle weakness and serum potassium levels as low as 1.1mEq/l. Shewas suspected of having Bartter's syndrome because of hypokalemia, metabolic alkalosis, hyperreninemia, hyperaldosteronism and normotension. Pretibial edema developed in for which she received 40 to 100 mg/week of furosemide intermittently for the next 5 years. Her serum potassium level ranged from 1.5 to 3.9mEq/l. In 1991, her serum creatinine level rose to 2.1mg/dl, then continued to increase gradually. She was admitted to our hospital in 1994 for evaluation of the renal dysfunction . Decreased creatinine clearance (44 ml/min) and a defect in urinary concentrating capacity (Fishberg's test, 370mOsm/kg⋅H₂O) were detected. Renal biopsy revealed juxtaglomerular cell hyperplasia. These findings resulted in the diagnosis of Bartter's syndrome. The renal biopsy also showed diffuse interstitial fibrosis and marked tubular atrophy. We postulate in this case that long-term hypokalemia due to Bartter's syndrome and the administration of furosemide led to chronic interstitial nephritis and renal dysfunction.

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