Effect of low-density lipoprotein apheresis on plasma endothelin-1 levels in diabetic hemodialysis patients with arteriosclerosis obliterans.

Endothelin (ET)-1 has been implicated in the pathogenesis of diabetes, arteriosclerosis, and chronic renal failure. We studied whether low-density lipoprotein (LDL) apheresis alters plasma ET-1 levels in diabetic hemodialysis patients with arteriosclerosis obliterans (ASO). Plasma ET-1 levels were measured in 30 healthy control subjects (Group A), 30 diabetes patients without ASO (Group B), 20 diabetes patients with ASO (Group C), 20 diabetes patients without ASO who were undergoing hemodialysis (Group D), and 6 diabetes patients with ASO who were undergoing hemodialysis (Group E). Hemodialysis patients were dialyzed three times weekly with a bicarbonate dialysate. Six diabetic hemodialysis patients with ASO underwent LDL apheresis once weekly for 10 weeks, and the change in plasma ET-1 levels due to LDL apheresis was measured. LDL apheresis resulted in a statistically significant decrease in levels of total cholesterol and LDL cholesterol. In addition, LDL apheresis improved clinical symptoms in all patients. Plasma ET-1 levels in Group E (15.0+/-1.9 pg/ml) were significantly higher than those in Groups A (1.0+/-0.6 pg/ml, P<.001), B (1.3+/-0.5 pg/ml, P<.001), C (5.6+/-1.0 pg/ml, P<.001), and D (10.4+/-1.6 pg/ml, P<.01). Plasma ET-1 levels decreased progressively and significantly after a single LDL apheresis began (9.4+/-1.0 pg/ml after 60 min, P<.001, and 6.0+/-1.0 pg/ml after 120 min, P<.001). These data suggest that ET-1 may be associated with arteriosclerosis and that LDL apheresis enhances peripheral microcirculation in part by reducing the production of ET-1 in diabetic hemodialysis patients with ASO.

Hemoperfusion with polymyxin B-immobilized fiber in septic patients with methicillin-resistant Staphylococcus aureus-associated glomerulonephritis.

BACKGROUND/AIMS: We investigated whether urinary podocytes are present in septic patients with methicillin-resistant Staphylococcus aureus (MRSA)-associated glomerulonephritis and whether polymyxin B-immobilized fiber (PMX-F) treatment affects proteinuria and urinary podocyte excretion in these patients. METHODS: Twenty septic patients with MRSA-associated glomerulonephritis (mean age: 63.7 years) and 80 septic patients whose MRSA infection was not followed by glomerulonephritis (mean age: 60.5 years) were included in this study. All septic patients were treated with fosfomycin sodium, beta-lactams, arbekacin sulfate, and teicoplanin, or a combination of these. Twenty septic patients with MRSA-associated glomerulonephritis were randomly assigned to one of two treatments: PMX-F treatment (group A, n = 10) and conventional treatment (group B, n = 10). PMX-F treatment was repeated twice. RESULTS: Urinary podocytes and urinary protein excretion were not detected in MRSA septic patients without glomerulonephritis. However, urinary podocytes (1.7 +/- 0.6 cells/ml) and proteinuria (2.6 +/- 0.6 g/d) were detected in the 20 septic patients with MRSA-associated glomerulonephritis. Plasma endotoxin levels were decreased from 13.6 +/- 4.6 pg/ml to 6.6 +/- 2.2 pg/ml (p < 0.05) in group A. Levels in group B, however, showed little difference after treatment. Urinary podocytes were reduced in group A (from 1.8 +/- 0.6 cells/ml to 0.4 +/- 0.2 cells/ml, p < 0.01) as was urinary protein excretion (from 3.0 +/- 0.5 g/d to 0.8 +/- 0.4 g/d, p < 0.01) but urinary podocytes and protein excretion levels showed little difference after treatment in group B. CONCLUSION: PMX-F treatment may be effective in reducing urinary protein and urinary podocyte excretion in septic patients with MRSA-associated glomerulonephritis.

Hemoperfusion with polymyxin B immobilized fibers for urinary albumin excretion in septic patients with trauma.

We investigated whether microalbuminuria/urinary creatinine ratio (MACR) is increased in septic patients with trauma and whether polymyxin B immobilized fiber (PMX-F) treatment decreases MACR. Twelve trauma patients without sepsis, 18 trauma patients with sepsis, and 10 healthy controls were included in this study. The 18 trauma patients with sepsis were randomly assigned to one of two groups, PMX-F treatment or conventional treatment. Urinary microalbumin and creatinine were measured before and after treatment. Plasma endotoxin levels were determined by endospecy test. Hemoperfusion with PMX-F was carried out twice, for 2 hours, at a flow rate of 100 ml/min. MACR increased in the 30 trauma patients (5.2+/-2.2 mg/mmol) in comparison to that in the healthy controls (1.0+/-0.6 mg/mmol, p < 0.01). In the 18 trauma patients with sepsis, MACR after sepsis (16.6+/-4.8 mg/mmol) was significantly greater than that before sepsis (5.5+/-2.3 mg/mmol, p < 0.01). There was a significant correlation between plasma endotoxin levels and MACR in septic trauma patients (p < 0.001). MACR was reduced from 17.0+/-5.0 mg/mmol to 4.2+/-1.5 mg/mmol (p < 0.01) with PMX-F, and plasma endotoxin levels were also reduced from 34.5+/-18.5 pg/ml to 10.8+/-6.6 pg/ml (p < 0.01). Neither MACR nor plasma endotoxin levels were affected by conventional treatment, however. In summary, trauma patients with sepsis appear to show increased MACR, and PMX-F therapy may be effective for attenuating the increase in MACR.

Effect of cerivastatin on proteinuria and urinary podocytes in patients with chronic glomerulonephritis.

BACKGROUND: We previously reported urinary podocytes to be a marker of glomerular injury. The aim of the present study was to determine whether cerivastatin, a newly developed, potent synthetic statin, affects proteinuria and urinary podocyte excretion in patients with chronic glomerulonephritis (CGN). METHODS: We randomly assigned 40 normotensive hypercholesterolemic patients with CGN to receive either cerivastatin 0.15 mg/day (n=20) or placebo (n=20). Subjects comprised 24 men and 16 women, with a mean age of 40.8+/-14.4 years; 27 had IgA nephropathy and 13 had non-IgA proliferative glomerulonephritis. Treatment was continued for 6 months. Plasma total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides, urinary protein excretion and the number of podocytes were measured before treatment and at 3 and 6 months after treatment. RESULTS: After 6 months, a significant reduction in total cholesterol (P<0.001), LDL-cholesterol (P<0.001) and triglycerides (P<0.05), and a significant increase in HDL-cholesterol (P<0.001) were observed in the group treated with cerivastatin. Urinary protein excretion decreased from 1.8+/-0.6 to 0.8+/-0.4 g/day, (P<0.01) in this group, and urinary podocyte excretion decreased from 1.6+/-0.6 to 0.9+/-0.4 cells/ml (P<0.01). However, placebo showed little effect on these lipid levels, urinary protein excretion and urinary podocyte excretion. The differences between the cerivastatin group and the placebo group were significant (cholesterol, P<0.001; LDL-cholesterol, P<0.001; triglycerides, P<0.05; HDL-cholesterol, P<0.001; urinary protein, P<0.01; and urinary podocytes, P<0.01). CONCLUSION: Statins such as cerivastatin may be beneficial for restoration of injured podocytes in patients with CGN and hypercholesterolaemia.

Effect of phosphodiesterase III inhibitor on plasma concentrations of endothelin-1 and tumour necrosis factor in patients with acute heart failure.

OBJECTIVE: Effects of loprinone hydrochloride on plasma ET-1 and TNF-alpha levels were assessed in patients with acute heart failure (AHF). METHODS AND RESULTS: Thirty patients with AHF were divided into 2 groups and treated with loprinone hydrochloride (0.3 pg/kg/min) (n = 15) or placebo (n = 15). Twenty healthy controls were also included. Plasma ET-1 and TNF-alpha were significantly higher in the 30 AHF patients than in the healthy controls. In AHF patients, loprinone hydrochloride lowered plasma ET-1 and TNF-alpha (p < 0.01). CONCLUSION: ET-1 and TNF-alpha may play pathophysiological roles in the progression of AHF. Loprinone hydrochloride is effective in reducing plasma ET-1 and TNF-alpha levels in AHF patients.

Effect of dilazep dihydrochloride on serum cardiac troponin T levels in hemodialysis patients.

BACKGROUND/AIM: Cardiac troponin T is a highly sensitive marker for the detection of myocardial injury. We studied whether dilazep dihydrochloride affects cardiac troponin T levels in hemodialysis patients. METHODS: Our study included 60 hemodialysis patients without symptoms of acute myocardial ischemia. We measured serum cardiac troponin T levels by the Elecsys troponin T assay and randomized 40 hemodialysis patients with left ventricular hypertrophy (LVH) into two treatment groups: a dilazep dihydrochloride group (300 mg/day, n = 20) and a placebo group (n = 20). Treatment was continued for 12 months. RESULTS: There were no significant differences between pre- and postdialysis cardiac troponin T levels before treatment. LVH was noted in 40 patients out of 60 hemodialysis patients (67%). Cardiac troponin T levels were significantly higher in these patients (0.23 +/- 0.08 microg/l) than in hemodialysis patients without LVH (0.09 +/- 0.03 microg/l). Cardiac troponin T levels were reduced from 0.24 +/- 0.08 to 0.12 +/- 0.06 microg/l (p < 0.01) in patients treated with dilazep dihydrochloride. There were no change in cardiac troponin T levels in patients receiving placebo (from 0.21 +/- 0.08 at baseline to 0.20 +/- 0.07 microg/l). CONCLUSION: Dilazep dihydrochloride may be effective in ameliorating myocardial damage in hemodialysis patients.

Effects of hemoperfusion on serum cardiac troponin T concentrations using polymyxin B-immobilized fibers in septic patients undergoing hemodialysis.

We investigated whether serum cardiac troponin T levels are altered in septic patients undergoing hemodialysis and whether polyinyxin B-immobilized fiber (PMX-F) treatment affects these levels. Fourteen heinodialysis patients with sepsis, 14 hemodialysis patients without sepsis, and 12 age matched healthy controls were included in this study. Cardiac troponin T levels in hemodialysis patients with sepsis (0.56+/-0.28 microg/L) were higher than levels in hemodialysis patients without sepsis (0.16+/-0.06 microg/L, p < 0.01) and healthy control subjects (0.03+/-0.01 microg/L, p < 0.001). The 14 hemodialysis patients with sepsis were randomly assigned to one of two treatment approaches: PMX-F treatment (n = 7) or conventional treatment (n = 7). Plasma endotoxin levels were significantly reduced from 46.6+/-17.8 pg/mI to 8.2+/-2.4 pg/ml, p < 0.01, in patients treated with PMX-F, and serum cardiac troponin T levels were also reduced from 0.62+/-0.30 microg/L to 0.26 = 0.12 microg/L, p < 0.05. Cardiac troponin T levels were unchanged in patients under conventional treatment. These data suggest that cardiac troponin T is indeed elevated in septic patients undergoing hemodialysis and niay reflect subclinical myocardial cell damage. PMX-F is effective in reducing myocardial damage, in part, due to reducing plasma endotoxin levels.