Circadian Blood Pressure Rhythm Is Changed by Improvement in Hypoalbuminemia and Massive Proteinuria in Patients with Minimal Change Nephrotic Syndrome.

BACKGROUND: Proteinuria and nighttime blood pressure (BP) elevation are notable risk markers of chronic kidney disease and correlate closely with each other. However, daily urinary protein excretion (UPE) always fluctuates. In patients with minimal change nephrotic syndrome (MCNS), serum albumin concentrations (SAC) decrease but fluctuate less than UPE. We evaluated whether SAC is a reliable marker for proteinuria, and compared the relations among circadian BP changes, SAC, and UPE. METHODS: In patients with MCNS (12 men and 11 women, 43 ± 18 years), blood and spot urine samples were collected on three consecutive days before treatment, and 24-hour BP was also measured on the three days. Then, an intervention study was conducted in the patients to examine circadian BP changes induced by treatment. Sleeping/waking BP ratio was analyzed as an indicator of circadian BP rhythm. RESULTS: In the three-day measurements before treatment, mean coefficient of variation, an index of dispersion of data, for SAC was 7.4 ± 7.4%, which was markedly lower (p < 0.01) than 35.7 ± 15.4% for UPE. SAC correlated inversely with sleeping/waking systolic and diastolic BP ratios on all three days, whereas UPE did not correlate significantly with sleeping/waking diastolic BP ratio on day 3. Sleeping/waking systolic and diastolic BP ratios were 96 ± 5 and 95 ± 6%, and were higher (p < 0.05) than in healthy subjects (89 ± 8 and 88 ± 10%). Treatment improved hyperproteinuria and hypoalbuminemia, and was accompanied by decreases (p < 0.05) in sleeping and waking systolic/diastolic BP ratio to 91 ± 8 and 89 ± 9%. CONCLUSION: These findings suggest that reduced SAC in patients with proteinuria is associated with disrupted circadian BP rhythm.

Relation between circadian blood pressure rhythm and serum albumin level in non-diabetic patients with proteinuria.

It remains unclear whether the abnormal circadian blood pressure (BP) rhythm in non-diabetic chronic kidney disease (CKD) is related to hypoalbuminemia. We evaluated relationships between circadian BP rhythm and serum albumin concentration (SAC) and also examined autonomic nervous activities. Non-diabetic CKD patients with proteinuria (n = 197; 105 men, 92 women; aged 47.0 ± 13.3 years; estimated glomerular filtration rate ≥30 ml/min) were divided into nephrotic syndrome (NS: n = 46, SAC ≤ 30 g/l), hypoalbuminemia (n = 65, 30 < SAC < 40 g/l) and normoalbuminemia (n = 86, SAC ≥ 40 g/l) groups. Non-proteinuria subjects (n = 97, urinary protein/creatinine ratio < 30 mg/g creatinine) were enrolled as the non-proteinuria group. Ambulatory 24 h BP monitoring was conducted in all subjects. Simultaneously, power spectral analysis of heart rate was performed to evaluate the sympathovagal balance. Waking BP was lower in the hypoalbuminemia and NS groups than the other groups. Sleeping/waking mean BP ratio was not different between non-proteinuria (0.87 ± 0.07) and normoalbuminemia (0.89 ± 0.08) groups, but increased significantly (p < 0.05) in the hypoalbuminemia (0.92 ± 0.08) and NS groups (0.96 ± 0.08). Significant reverse correlations were observed between SAC and sleeping/waking mean BP ratio (r = -0.274, p < 0.001) in all patients. Multivariate regression analysis identified SAC and sympathovagal balance as predictors of increased sleeping/waking BP ratios as the dependent variable. In non-diabetic CKD patients with proteinuria, disturbed circadian BP rhythms were related to SAC and 24 h sympathovagal imbalance.

Effects of the oriental herbal medicine Bofu-tsusho-san in obesity hypertension: a multicenter, randomized, parallel-group controlled trial (ATH-D-14-01021.R2).

OBJECTIVE: There is no clinical evidence that supports the benefit of integrative medicine, defined as combination therapy of oriental and western medicine, on obesity-related hypertension. This study evaluates the efficacy of Bofu-tsusho-san (BOF), an oriental herbal medicine, on the ambulatory blood pressure (BP) profile in hypertensive patients with obesity. METHODS: The study design was a multicenter, randomized, open-label, parallel-group controlled trial in 107 hypertensive patients with obesity. Participants were randomly assigned to receive either the conventional control therapy or BOF add-on therapy. In both groups antihypertensive therapy was aimed at achieving the target clinic BP. The primary outcome was change in the ambulatory BP profile from baseline to 24 weeks after randomization. RESULTS: Daytime systolic BP variability, an important parameter of ambulatory BP profile, was decreased in the BOF group, and the difference in the changes in daytime systolic BP variability was significant between the BOF and control group (Control vs BOF; the change from baseline in daytime systolic BP variability, 1.0±3.3 vs -1.0±3.3%; p=0.006). CONCLUSION: The BOF add-on therapy effectively improved the ambulatory BP variability. This is the first report suggesting that an integrative medicine approach may exert favorable effects on obesity-related hypertension compared with conventional pharmaceutical treatment. CLINICAL TRIAL REGISTRATION: UMIN000003878.

Effects of doxazosin as the third agent on morning hypertension and position-related blood pressure changes in diabetic patients with chronic kidney disease.

We conducted a prospective study to assess the effects of doxazosin, as the third agent, on morning and position-related blood pressure (BP) in 77 diabetic patients with chronic kidney disease, who were allocated randomly to doxazosin and diuretics groups. Doxazosin decreased morning BP but diuretics could not decrease pre-awakening diastolic BP. Only doxazosin improved sympathovagal balance. Doxazosin and diuretics decreased standing and sitting BP but only doxazosin improved sympathovagal balance regardless of body positions. Doxazosin did not decrease absolute BP changes shortly after standing. In diabetic patients, doxazosin decreased morning BP through improving sympathovagal balance without causing significant orthostatic hypotension (ClinicalTrials.gov number, NCT00295555).

Effects of atorvastatin versus probucol on low-density lipoprotein subtype distribution and renal function in hyperlipidemic patients with nondiabetic nephropathy.

OBJECTIVES: Small dense low-density lipoprotein (LDL) plays an important role in glomerular injury through conversion to an oxidatively modified form of LDL. However, few studies have evaluated the effects of antilipidemic agents on the LDL particle size and renal function in hyperlipidemic patients with nondiabetic nephropathy. METHODS: This study was a randomized crossover trial comparing the effects of atorvastatin (10 mg/day) and probucol (500 mg/day) administered for 24 weeks in 31 patients (urinary albumin excretion 0.3-2.0 g/day and creatinine clearance >30 mL/min/1.73 m (2) ). Lipid parameters, mean LDL particle diameter, creatinine clearance, and urinary albumin to creatinine excretion ratio were measured before and during treatment periods. MAIN FINDINGS: Atorvastatin and probucol significantly reduced the serum total cholesterol and LDL cholesterol concentrations. When stratified by mean baseline LDL particle size at 25.5 nm, atorvastatin increased (p < 0.05) LDL particle size from 24.6 +/- 0.5 to 25.2 +/- 0.9 nm only in the <25.5 nm (pattern B) group, whereas probucol decreased (p < 0.05) LDL size from 24.8 +/- 0.9 to 24.2 +/- 0.9 nm in the pattern B group and from 25.9 +/- 0.5 to 24.6 +/- 0.8 nm in the >or=25.5 nm (pattern A) group. No significant differences in urinary albumin/creatinine excretion ratio and creatinine clearance were observed in both groups during treatment. CONCLUSIONS: Only atorvastatin improved the LDL-subtype distribution in hyperlipidemic patients with nondiabetic nephropathy, although both agents exhibited no renoprotective action, suggesting that the effects on LDL-subtype distribution do not directly lead to renoprotection.

Effects of losartan and amlodipine on urinary albumin excretion and ambulatory blood pressure in hypertensive type 2 diabetic patients with overt nephropathy.

OBJECTIVE: Few studies have assessed whether 24-h blood pressure control induced by antihypertensive agents improves macroalbuminuria in hypertensive type 2 diabetic patients with overt nephropathy. We evaluated the effects of losartan and amlodipine on 24-h blood pressure, autonomic nervous activity, and albuminuria in these patients. RESEARCH DESIGN AND METHODS: In this open-label, parallel-prospective, randomized study, 44 patients were treated with losartan and 43 with amlodipine for a 12-week titration phase and a maintenance phase for a maximum of 12 weeks. Twenty-four-hour blood pressure and urinary albumin excretion were measured before and during treatment. Simultaneously, power spectral analysis of heart rate was performed to evaluate low frequency (LF) and high frequency (HF) components and LF-to-HF ratios as an index of sympathovagal balance. RESULTS: Losartan decreased (P < 0.001) mean blood pressure from 162/91 to 150/82 mmHg during daytime and from 146/82 to 137/74 mmHg during nighttime (systolic/diastolic). Amlodipine also decreased (P < 0.001) blood pressure from 159/90 to 147/82 mmHg during daytime and from 143/81 to 131/72 mmHg during nighttime. LF and HF components and nighttime-to-daytime ratios for the LF-to-HF ratios did not differ during treatment in two groups, showing no changes in the diurnal autonomic nervous rhythm. Losartan decreased (P < 0.001) 24-h urinary albumin excretion from 810 mg/day (95% CI 780-1,140) to 570 (510-910). Amlodipine, however, did not decrease (P = 0.893) albuminuria (790 mg/day [780-1,170] vs.790 [710-1,260]). CONCLUSIONS: These results suggest that in type 2 diabetes with overt nephropathy, 24-h blood pressure regulation alone is inadequate to reduce macroalbuminuria and additional effects of losartan are crucial for antiproteinuric action.

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.