Long-term efficacy and safety of the small-sized ß2-microglobulin adsorption column for dialysis-related amyloidosis.

Dialysis-related amyloidosis (DRA) is one of the major complications often seen in long-term dialysis patients, and is one of the factors that decreases quality of life. ß2-microglobulin (ß2-m) is considered to be a major pathogenic factor in dialysis-related amyloidosis. The Lixelle adsorbent column, with various capacities, has been developed to adsorb ß2-m from the circulating blood of patients with dialysis-related amyloidosis. Using a minimum type of ß2-m-adsorbing column (Lixelle S-15), we evaluated its therapeutic efficacy and safety in dialysis patients. Seventeen hemodialysis patients with DRA were treated with the S-15 column for one year. Treatment was performed three times a week in this study. During the study period, pinch strength, visual analog scale for joint pain, and activities of daily living were evaluated every three months, and blood sampling was performed every six months. After one year's treatment with the S-15 column, the ß2-m level decreased from 29.3±9.6mg/L to 24.7±5.1mg/L (P<0.05), and the high sensitive C-reactive protein level decreased from 2996±4380ng/mL to 1292±1774ng/mL. After one year of S-15 column use, pinch strength increased from 5.9±3.0pounds to 7.2±3.2pounds (P<0.05), and the visual analog scale for joint pain and activities of daily living score also improved. Long-term use of the Lixelle S-15 column is safe and effective for improvement of quality of life in chronic dialysis patients. Improvement of chronic inflammation may be one of the mechanisms through which the beneficial effects of the column is effected.

Effects of multiple factorial intervention on ambulatory BP profile and renal function in hypertensive type 2 diabetic patients with overt nephropathy - a pilot study.

Accumulating evidence has shown that diabetic patients are increasing in number, and renal and cardiovascular complications are the most common cause of death in diabetic patients. Thus, it would be of considerable value to identify the mechanisms involved in the progression of renal impairment and cardiovascular injury associated with diabetes. Recent evidence also indicated that multifactorial intervention is able to reduce the risk of cardiovascular disease and death among patients with diabetes and microalbuninuria. In this pilot study, we examined the effects of intensified multifactorial intervention, with tight glucose regulation and the use of valsartan and fluvastatin on ambulatory blood pressure (BP) profile, estimated glomerular filtration rate (eGFR), and urinary albumin to creatinine ratio (UACR), in 20 hypertensive patients (16 male and 4 female) with type 2 diabetes mellitus and overt nephropathy. After 12 months of intensified treatment, office BP, fasting plasma glucose (FPG), and low-density lipoprotein cholesterol (LDLC) were significantly decreased compared to baseline (systolic blood pressure (SBP), 130 ± 2 vs. 150 ± 1 mmHg; diastolic blood pressure (DBP), 76 ± 1 vs. 86 ± 1 mmHg; FPG, 117 ± 5 vs. 153 ± 7 mg/dl; LDLC, 116 ± 8 vs. 162 ± 5 mg/dl, P < 0.0001). Also, compared to the baseline values, the daytime and nighttime ambulatory BP and short-term BP variability were significantly decreased after 12 months. Furthermore, while eGFR was not altered (44.3 ± 5.1 vs. 44.3 ± 6.5 ml/min/1.73 m(2), not significant (NS)), UACR showed a significant reduction after 12 months of intensified treatment (1228 ± 355 vs. 2340 ± 381 mg/g-cr, P < 0.05). These results suggest that the intensified multifactorial intervention is able to improve ambulatory BP profile, preserve renal function, and reduce urinary albumin excretion in type 2 diabetic hypertensive patients with overt nephropathy.

Safety and efficacy of fluvastatin in hyperlipidemic patients with chronic renal disease.

BACKGROUND: There are few reports on the safety and efficacy of long-term treatment with statins in patients with chronic renal disease and hyperlipidemia. We evaluated these subjects treated with fluvastatin. METHODS: After a 4-week run-in period, a total of 80 patients with diabetic nephropathy or chronic glomerulonephritis were randomly allocated to receive dietary therapy and fluvastatin 20 mg/day (n=39), or dietary therapy alone (n=41) for a period of 48 weeks. Lipid parameters, rhabdomyolysis-related indicators, 24-hour urinary albumin excretion and creatinine clearance were measured. The pharmacokinetics of fluvastatin was examined in 8 patients. RESULTS: Creatinine clearance and 24-hour urinary albumin excretion did not differ between the two groups. The peak serum fluvastatin concentration (Cmax) was 141+/-67 microg/L and the mean AUC0-6 h was 341+/-149 microgh/L. Fluvastatin treatment significantly lowered serum total cholesterol, low-density lipoprotein (LDL) cholesterol and apo-lipoprotein B concentrations by 16%, 25%, and 22%, respectively, compared with patients receiving dietary therapy alone. There were no significant differences in serum triglyceride and high-density lipoprotein (HDL) cholesterol concentrations between the two treatment groups. Serum creatine kinase and aldolase concentrations did not change throughout treatment in both groups. CONCLUSIONS: Fluvastatin treatment significantly improved lipid parameters in patients with chronic renal disease. Fluvastatin was well tolerated, with no adverse effects on renal function and no muscular toxicity. However, the drug showed no direct renoprotective effects.

Perindopril effects on ambulatory blood pressure: relation to sympathetic nervous activity in subjects with diabetic nephropathy.

BACKGROUND: Few studies have reported the effect of angiotensin-converting enzyme inhibitors on 24-h blood pressure (BP) and regulation of sympathetic nervous activity in hypertensive patients with diabetic nephropathy. Using ambulatory BP monitoring (ABPM) devices equipped with spectral analysis of heart rate variability, we assessed the effects of perindopril on 24-h BP and autonomic nervous activity in these patients. METHODS: Thirty-four hypertensive patients with non-insulin-dependent diabetic nephropathy underwent ABPM before and after treatment with perindopril (final dose: 4.9 +/- 1.8 mg/d). Simultaneously, spectral analysis was performed to calculate the high frequency components (HF) as a marker of parasympathetic nervous activity, and the low frequency components (LF)/HF ratios as an index of the sympathovagal balance. RESULTS: Perindopril significantly and equally decreased the waking and sleeping BP in the diabetic patients. During the sleeping period, the magnitude of change of mean BP induced by perindopril correlated inversely with the sleeping/waking ratio of mean BP before treatment. However, there was no correlation between these parameters during the waking period. Perindopril decreased both waking and sleeping LF/HF ratios, although no differences in HF components were observed between before and after treatment. CONCLUSIONS: In patients with diabetic nephropathy, perindopril decreased 24-h BP. Spectral analysis suggested that this finding was partially related to inhibited sympathetic nervous activity. During sleeping periods, the BP-lowering effect of perindopril was more pronounced in patients showing no nocturnal decrease in BP. Perindopril may be a potent antihypertensive agent to reduce increased nocturnal BP, a risk factor of target organ damage in these patients.