To assess the chronic antihypertensive and renal protective effects of the specific angiotensin II receptor antagonist, CS-866, in the remnant kidney model of chronic renal failure, we administered it alone or in combination with temocapril, an angiotensin converting enzyme inhibitor, to 5/6 nephrectom ized spontaneously hypertensive rats (SHR) for 8 weeks. At the age of 10 weeks, 5/6 nephrectomized SHR were allocated to receive two doses of CS-866 (CS-3;3 mg/kg/day, or CS-10;10 mg/kg/day), temocapril (TEM ; 10 mg/kg/day), a combination of CS-866 (3 mg/kg/day) and temocapril (10 mg/kg/day) or the vehicle alone via oral gavage for 8 weeks. Systolic blood pressure (SBP) and urinary protein excretion (UprotV) were measured every two weeks. At the age of 18 weeks, the rats were decapitated and the blood, remnant kidney, aorta and heart were collected and used for biochemical measurements and histopathological studies. There was no significant difference in body weight among the groups during the study. All drug treatments significantly reduced SBP, UprotV, glomerular sclerosis index (GSI), relative interstitial volume (RIV) and the heart weight to body weight ratio. The hypoten sive effects were in the order of combination therapy> CS-10=TEM> CS-3. For correlational analysis, we used values for SBP and UprotV derived from the average of values in rats over the age of 12 weeks through 18 weeks. UprotV, GSI and RIV were found to be highly correlated with SBP among the individual rats pooled from all groups (r=0.511, r=0.754, r=0.817, respectively) and the correlation was maintained among the group means (r=0.945, r=0.989, r=0.918, respectively). Furthermore, the heart weight to body weight ratio was found to be highly correlated with SBP among the individual rats pooled from all groups (r=0.923) and the correlation was maintained among the group means (r=0.996). We conclude that organ protective effects of CS-866, TEM, or combination therapy are closely related to the magnitude of their antihypertensive effects.

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Nutritional status is one of the most important factors affecting mortality and morbidity in chronic dialysis patients. There are, however, few data on serial body composition changes in these patients. To investigate serial changes in body composition in patients on peritoneal dialysis, we measured intracellular fluid volume (ICF), extracellular fluid volume (ECF), body protein volume (BPV), body fat volume (BFV) and bone mineral content (BMC) using multifrequency bioelectrical impedance analysis (MF-BIA) . MF-BIA was performed in 35 patients, consisting of 21 men and 14 women with a mean age of 51.3±10.9 years, before and after one year of observation. At the baseline in male patients, ICF was 37.0±3.4 %, ECF 19.7±1.6 %, BPV 20.7±1.7 %, BFV 18.1±6.6 % and BMC 4.5±0.4 % of body weight, and in female patients ICF was 34.4±2.6 %, ECF 17.8±1.9 % BPV 19.0±1.6 %, BFV 24.4±6.2 % and BMC 4.5±0.4 % of body weight. In the group of patients whose body weight increased more than 3 kilograms (n=9), the increase rate of BFV was 32.3±20.2 %, significantly higher than that of the other segments (p < 0.001) . On the other hand, in the group of patients whose body weight decreased more than 3 kilograms (n=5), each segment showed the same extent of decrease and there was no significant difference in the decrease rates among each segment. In the group of patients whose body weight was stable (n=21), changes in each body composition segment were extremely small. It could be concluded that the body weight increase is due mainly to increase in BFV and body weight decrease results from a concurrent decrease in each body composition segment in peritoneal dialysis patients.

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The first choice of therapy for nephrotic syndrome is steroid, and cyclosporin A (CyA) or other immunosuppressants are selected for steroid resistant or recurrent cases. Nephrotic syndrome accompanies hyperlipidemia for which HMG-CoA reductase inhibitors are mainly used. On the other hand, probucol is used in cases showing inadequate effects or some adverse reactions under treatment with HMG-CoA reductase inhibitors. Recently, we experienced several cases whose blood levels of CyA were decreased to about half that before the combined use of probucol, and concomitant administrations were discontinued. Based on these cases, we considered that the use of probucol should be proscribed in patients with nephrotic syndrome accompanying hyperlipidemia giving preference to CyA treatment. In cases of unavoidable usage of probucol, CyA dose adjustments are required on the basis of frequent CyA blood level monitoring.

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To investigate the effect of doxazosin on orthostatic blood pressure changes with daily activity, the relationship among blood pressure, physical position and physical activities using an ambulatory multibiomedical monitoring system (TM2425) were studied. The subjects were 22 patients with essential hypertension(EHT group), 23 patients with diabetic mellitus(DM group) and 17 healthy volunteers for the control. Patients were administered doxazosin at 2-8 mg/day for 0.5 month to 12 months. Twentyfour-hour blood pressure, posture and activity were monitored. Systolic blood pressure was higher in the standing position than that in the sitting position in the control group, but there were no differences between these values in the EHT group and DM groups. During the awake, sleep, and standing periods, doxazosin significantly decreased blood pressure in the EHT group ; however, it significantly decreased only the standing systolic blood pressure in the DM group. Absolute changes in blood pressure after the administration of doxazosin were not significantly different between the standing and sitting periods in each group. These findings suggest that doxazosin decreases the blood pressure of both patients with essential hypertension and patients with diabetic mellitus without an excessive decrease in standing blood pressure.

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Nephrotic syndrome frequently causes thromboembolic complications in veins. Arterial thrombosis, however, is relatively rare. We report the case of a 47-year-old male with nephrotic syndrome complicated with abdominal aortic thrombosis. The patient complained of pain in the bilateral lower extremities 2 weeks after the development of nephrotic syndrome. The aortogram revealed complete occlusion of the abdominal aorta just below the origin of the inferior mesenteric artery. Necrosis of the legs extended rapidly, and he eventually lost his legs. Among various predisposing factors, hypercoagulability associated with nephrotic syndrome seemed to be responsible for the development of thrombosis. Thrombotic complications are sometimes serious in the nephrotic patient. Assessment for the risk factors is required to warrant prophylactic anticoagulation.

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A 51-year-old male who had been working as a building wrecker for 20 years, was admitted to our hospital in June 1999 for proteinuria and hematuria examination. He started this work in 1978. Twelve years later, severe coughing and bloody sputum began and he was diagnosed as having silicosis in 1995. Urinalysis on admission showed proteinuria (294 mg/day), microhematuria (20-30/hpf), RBC cast and granular cast. High serum IgA (770 mg/dl) and high serum interleukin-6 (IL-6) (3, 280 pg/dl) were found. A renal biopsy showed mild mesangial matrix expansion and mesangial cell proliferation with IgA deposition, which was diagnosed as IgA nephropathy. Chest X rays showed multiple small nodular lesions on both lung fields indicating silicosis. In Nov. 1999, he resigned from his job as a building wrecker because of increasing coughing and bloody sputum associated with body weight loss. Within 3 months after stopping this work, coughing and bloody sputum disappear ed and the abnormal urinalysis findings returned to normal. Serum IgA and serum IL-6 data improved to 462 mg/dl and 2.5 pg/dl, respectively. It is suggested that silicon exposure might be related to the pathogenesis of IgA nephropathy in this patient.

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