Improved home BP profile with dapagliflozin is associated with amelioration of albuminuria in Japanese patients with diabetic nephropathy: the Yokohama add-on inhibitory efficacy of dapagliflozin on albuminuria in Japanese patients with type 2 diabetes study (Y-AIDA study).

BACKGROUND: The Y-AIDA study was designed to investigate the renal- and home blood pressure (BP)-modulating effects of add-on dapagliflozin treatment in Japanese individuals with type 2 diabetes mellitus (T2DM) and albuminuria. METHODS: We conducted a prospective, multicenter, single-arm study. Eighty-six patients with T2DM, HbA1c 7.0-10.0%, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min/1.73 m2, and urine albumin-to-creatinine ratio (UACR) ≥ 30 mg/g creatinine (gCr) were enrolled, and 85 of these patients were administered add-on dapagliflozin for 24 weeks. The primary and key secondary endpoints were change from baseline in the natural logarithm of UACR over 24 weeks and change in home BP profile at week 24. RESULTS: Baseline median UACR was 181.5 mg/gCr (interquartile range 47.85, 638.0). Baseline morning, evening, and nocturnal home systolic/diastolic BP was 137.6/82.7 mmHg, 136.1/79.3 mmHg, and 125.4/74.1 mmHg, respectively. After 24 weeks, the logarithm of UACR decreased by 0.37 ± 0.73 (P < 0.001). In addition, changes in morning, evening, and nocturnal home BP from baseline were as follows: morning systolic/diastolic BP - 8.32 ± 11.42/- 4.18 ± 5.91 mmHg (both P < 0.001), evening systolic/diastolic BP - 9.57 ± 12.08/- 4.48 ± 6.45 mmHg (both P < 0.001), and nocturnal systolic/diastolic BP - 2.38 ± 7.82/- 1.17 ± 5.39 mmHg (P = 0.0079 for systolic BP, P = 0.0415 for diastolic BP). Furthermore, the reduction in UACR after 24 weeks significantly correlated with an improvement in home BP profile, but not with changes in other variables, including office BP. Multivariate linear regression analysis also revealed that the change in morning home systolic BP was a significant contributor to the change in log-UACR. CONCLUSIONS: In Japanese patients with T2DM and diabetic nephropathy, dapagliflozin significantly improved albuminuria levels and the home BP profile. Improved morning home systolic BP was associated with albuminuria reduction. Trial registration The study is registered at the UMIN Clinical Trials Registry (UMIN000018930; http://www.umin.ac.jp/ctr/index-j.htm ). The study was conducted from July 1, 2015 to August 1, 2018.

Atherosclerosis of the carotid bulb is associated with the severity of orthostatic hypotension in non-diabetic adult patients: a cross-sectional study.

BACKGROUND: The carotid bulb has a high density of baroreceptors that play an important role in maintaining blood pressure. We hypothesized that atherosclerosis of the carotid bulb would reflect the severity of orthostatic hypotension more accurately than would atherosclerosis of other carotid artery segments. METHODS: This cross-sectional study included 198 non-diabetic adults. We measured the cardio-vascular ankle index as an index of arterial stiffness, intima-media thickness in each carotid artery segment (internal carotid artery, carotid bulb, distal and proximal portions, respectively, of the common carotid artery) as a measure of atherosclerosis, and heart rate variability as a measure of cardiac autonomic function. The sit-to-stand test was used to assess severity of orthostatic hypotension. RESULTS: Intima-media thickness of the carotid bulb was correlated with orthostatic systolic blood pressure change (r = -0.218, p = 0.002), cardio-ankle vascular index (r = 0.365, p < 0.001) and heart rate variability parameters. Multivariate regression analysis revealed that among all of the segments, only intima-media thickness of the carotid bulb was an independent predictor of orthostatic systolic blood pressure change (p = 0.022). CONCLUSION: Atherosclerosis of the carotid bulb was associated with severity of orthostatic hypotension, arterial stiffening and cardiac autonomic dysfunction than that of other carotid artery segments.

Effects of tolvaptan in patients with chronic kidney disease and chronic heart failure.

BACKGROUND: Tolvaptan, a vasopressin V2 receptor blocker, has a diuretic effect for patients with heart failure. However, there were a few data concerning the effects of tolvaptan in patients with chronic kidney disease (CKD). METHODS: We retrospectively analyzed 21 patients with chronic heart failure and CKD. Tolvaptan was co-administered with other diuretics in-use, every day. We compared clinical parameters before and after the treatments with tolvaptan. Furthermore, we examined the correlations between baseline data and the change of body weight. RESULTS: Tolvaptan decreased the body weight and increased the urine volume (p = 0.001). The urine osmolality significantly decreased throughout the study period. Urinary Na/Cr ratio and FENa changed significantly after 4 h, and more remarkable after 8 h (p = 0.003, both). Serum creatinine increased slightly after 1 week of treatment (p = 0.012). The alteration of body weight within the study period correlated negatively with the baseline urine osmolality (r = -0.479, p = 0.038), the baseline urine volume (r = -0.48, p = 0.028), and the baseline inferior vena cava diameter (IVCD) (r = -0.622, p = 0.017). Hyponatremia was improved to the normal value, and the augmentations of the sodium concentration were negatively associated with the basal sodium levels (p = 0.01, r = -0.546). CONCLUSIONS: Tolvaptan is effective in increasing diuresis and improved hyponatremia, even in patients with CKD. The baseline urine osmolality, urine volume, and IVCD may be useful predictors for diuretic effects of tolvaptan.

Role of renin-angiotensin system inhibitors in retardation of progression of end-stage renal failure: a retrospective study.

BACKGROUND: Few studies have examined how renin-angiotensin system inhibitors (RASI) delay dialysis initiation in patients with advanced chronic kidney disease (CKD). We conducted a retrospective survey to examine this subject. METHODS: We reviewed the records of patients with advanced CKD for the 60-month period before dialysis initiation between 1990 and 2015. Patients were classified based on the decade of dialysis initiation into the 1990s, 2000s, and 2010s groups. The rates of antihypertensive medications administered were assessed. The rate of decline of renal function was evaluated by the slope of reciprocal serum creatinine (SRSC). Multiple regression analyses were conducted to evaluate factors contributing to renoprotection. RESULTS: The duration of RASI administration was longer in the 2010s than in 2000s and 1990s. Both diabetic and non-diabetic patients had lower SRSC in the 2010s compared to the 2000s. In the 2010s, the rate of RASI administration during the 60-month pre-dialysis period showed an initial rise followed by a downward trend, although the rates of administration of the other classes of antihypertensives increased continuously. Multivariate regression analyses identified age, blood pressure, diuretics, α-blockers, α-methyldopa and RASI as independent predictors of SRSC in the 2010s. The rate of RASI administration correlated with serum potassium concentration. CONCLUSION: Our findings suggest that in the 2010s, RASI with other antihypertensive agents contributed to renoprotection in advanced CKD patients, but they were underused because of the concern over hyperkalemia. In real-world clinical practice, physicians may feel great hesitation in using RASI in patients with advanced CKD.

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.

Efficacy of cyclosporine combination therapy for new-onset minimal change nephrotic syndrome in adults.

BACKGROUND: Cyclosporine and prednisolone combination therapy has been used in the treatment of minimal change nephrotic syndrome (MCNS). However, few studies have evaluated the efficacy of cyclosporine combined with intravenous methylprednisolone pulse therapy (MPT) as a first-line treatment for new-onset MCNS. We conducted a retrospective clinical study to evaluate the efficacy and safety of cyclosporine combined with MPT and oral prednisolone for new-onset MCNS in adults. METHODS: Forty-six adult patients with biopsy-proven MCNS were analyzed retrospectively. This study included three groups. Group 1 (n = 17) was treated with intravenous MPT (0.5 or 1.0 g/day for 3 days) followed by oral cyclosporine (2-3 mg/kg/day) and prednisolone (30 mg/day). Group 2 (n = 15) was treated with intravenous MPT followed by oral prednisolone (0.4-0.8 mg/kg/day). Group 3 (n = 14) was treated with oral prednisolone (0.6-1.0 mg/kg/day) alone. RESULTS: The length of hospital stay was the shortest in Group 1 (P < 0.001). The mean duration to achieve <20 mg/day of prednisolone was also the shortest in Group 1 (P < 0.05). Complete remission rates were 100 % in Group 1, 85.7 % in Group 2, and 69.2 % in Group 3 during the 9-month follow-up (P = 0.073). The rate of adverse effects caused by prednisolone was less in Group 1 (P < 0.05). Multivariate analysis revealed that the independent determinants of durations of remission were the selectivity index (P = 0.004), eGFR (P = 0.001) and the use of cyclosporine (P = 0.045). CONCLUSIONS: Combination therapy with cyclosporine may be a beneficial treatment option for new-onset MCNS in adults because of its clinical efficacy and safety.

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).

Angiotensin receptor blocker (ARB)-diuretic versus ARB-calcium channel blocker combination therapy for hypertension uncontrolled by ARB monotherapy.

Diuretics or calcium channel blockers (CCBs) are used concomitantly with an angiotensin II receptor blocker (ARB). However, it is not established which ARB-based combination therapy is the most effective and safe. This prospective randomized open-label study compared the efficacy and safety of a fixed-dose tablet of losartan (LST)-hydrochlorothiazide (HCTZ) (n = 99) and LST-amlodipine (AML) (n = 77) in Japanese patients whose hypertension was uncontrolled by ARB monotherapy. Blood pressure changed similarly over the 12-month study period. Only LST-HCTZ significantly increased serum uric acid (SUA) in patients with low baseline SUA (<5.6 mg/dL) but not in patients with high baseline SUA.

Effects of carvedilol as third-line add-on therapy on blood pressure and glucose metabolism in type 2 diabetic patients with chronic renal disease stage 3 and above.

BACKGROUND: We evaluated the effect of coadministration of ß-blocker (carvedilol) as the third agent with angiotensin II receptor blockers (ARB) and calcium channel blockers (CCB) on blood pressure (BP) regulation and glucose metabolism. METHODS: Diabetic patients who did not achieve the therapeutic BP goal (140/90 mmHg) by ARB and CCB combination therapy were recruited. This study was designed to compare the BP regulating effects by adding carvedilol (10 mg/day, n=30) and by doubling the dose of either ARB (n=34) or CCB (n=31). Serum glucose metabolism was examined. RESULTS: The carvedilol group showed a decrease (P<0.01) in BP from 166±11/90±8 to 156±9/84±7 mmHg at 12 weeks. In the ARB and CCB groups, BP also decreased (P<0.01) from 164±11/87±8 to 153±10/83±8 and 163±7/87±8 to 153±8/84±9 mmHg at 12 weeks. The rates of achieving therapeutic goal at 12 weeks were 36.7% in the carvedilol, 38.2% in the ARB and 41.9% in the CCB group. Serum glucose metabolism did not change in all groups. CONCLUSIONS: These results suggest that adding carvedilol decreased BP as safely as increasing the dose of ARB or CCB in patients with diabetic nephropathy.

Relationship between basal sodium intake and the effects of dapagliflozin in albuminuric diabetic kidney disease.

We investigated the impact of basal dietary sodium intake on the dapagliflozin-induced changes in albuminuria and blood pressure (BP) measured at home in patients with diabetic kidney disease (DKD).This was a secondary analysis of the Y-AIDA Study, in which DKD patients with estimated glomerular filtration rate (eGFR) ≥ 45 ml/min/1.73 m2 and urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g creatinine were administered dapagliflozin for 24 weeks, and dapagliflozin significantly improved albuminuria levels and home BP profiles. The effects on UACR, home-measured BP, and eGFR were compared between high- and low-sodium intake groups (HS and LS groups), which were created using baseline urinary sodium-to-creatinine ratio of 84 participants with available basal sodium-to-creatinine ratios. At baseline, clinic-/home-measured BPs, UACR, and eGFR, were comparable in the two groups. After 24 weeks, the reductions from baseline in ln-UACR were comparable in the two groups. In contrast, the reductions in evening home systolic BP and eGFR from baseline were larger in HS than in LS (BP: - 13 ± 2.08 vs. - 6 ± 1.88, P = 0.020; eGFR: - 3.33 ± 1.32 vs. 0.37 ± 1.29, P = 0.049). The home BP-lowering effects of dapagliflozin are larger in HS than LS, concomitant with a larger reduction in eGFR, suggesting a dapagliflozin-induced improvement in glomerular relative hyperfiltration in HS.

Silent brain infarction and rapid decline of kidney function in patients with CKD: a prospective cohort study.

BACKGROUND: Several reports have found that chronic kidney disease (CKD) is an independent risk factor for stroke. However, little is known about whether cerebrovascular disease conversely predicts the outcome of kidney function. In view of the similarities between vascular beds of the kidney and brain, we hypothesized that silent brain infarction (SBI) could reflect the degree of injury in renal small vessels and predict the risk of progression of kidney disease. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 142 patients with CKD (stages 3-5) admitted to our clinic for education about CKD from January 2006 to July 2007 were recruited and followed up for 2 years. PREDICTOR: SBI. OUTCOMES: Composite primary outcomes: doubling of serum creatinine level, development of end-stage renal disease defined as dialysis or transplant, and death from cardiovascular causes. Secondary outcome: rate of decrease in estimated glomerular filtration rate. MEASUREMENTS: Brain magnetic resonance imaging was performed to determine the presence or absence of SBI. RESULTS: At baseline, 87 patients had SBI. During follow-up, 43 patients (30.3%) developed the following primary outcomes: doubling of serum creatinine level (8 patients), dialysis therapy (32 patients), and death from cardiovascular causes (3 patients). In crude analysis, the presence of SBI predicted time to primary outcomes (P=0.01). A multivariate Cox model confirmed the presence of SBI to be an independent predictor of study outcomes (HR, 2.16; 95% CI, 1.01-4.64; P=0.04). Estimated glomerular filtration rate decreased more in patients with SBI than in those without SBI (-0.11/y vs -0.06/y relative to baseline value; P=0.005). LIMITATIONS: Study size was small. CONCLUSION: We showed that SBI was an important independent prognostic factor for the progression of kidney disease in patients with CKD. Our findings suggest that patients with SBI should be considered a high-risk population for decreased kidney function.

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.

Relationship between silent brain infarction and chronic kidney disease.

BACKGROUND: The presence of silent brain infarction (SBI) increases the risk of symptomatic stroke and dementia. The association between SBI and chronic kidney disease (CKD) has not been clarified. Moreover, little is known about what factors are related to SBI in CKD patients and whether the prevalence of SBI differs in CKD stage or cause of CKD. METHODS: This is a cross-sectional study. A total of 375 subjects-335 with CKD and 40 with essential hypertension-were included. All subjects underwent magnetic resonance imaging (MRI) of the brain to detect SBI. Glomerular filtration rate (GFR) was estimated using Modification of Diet in Renal Disease equation, and cardiovascular risk factors were examined. RESULTS: The prevalence of SBI was 56.5% in all subjects. Among causes of CKD, hypertensive nephrosclerosis had a strong association with SBI. According to the estimated GFR (eGFR) stage, the more severe the stage of eGFR, the higher the prevalence of SBI (age-adjusted odds ratio [95% confidence interval] for eGFR 30-59, 15-29 and <15 versus >or=60 mL/min/1.73 m(2): 1.34 [0.68-1.99], 1.94 [1.30-2.57] and 2.51 [1.91-3.10]). In multivariate logistic analysis, eGFR was related to SBI independently, in addition to age and blood pressure (P = 0.025). However, other traditional and non-traditional risk factors were not. CONCLUSION: There was an independent association between eGFR and SBI. CKD patients should receive active detection of SBI and more intensive preventive management, especially for hypertension, should be needed in CKD patients to prevent SBI.

Evaluation of renal function and proteinuria based on mass health examinations in young Japanese obese adults.

BACKGROUND: Although obesity is recognized to be a risk factor for chronic kidney disease (CKD), few studies have reported the association between obesity and CKD in the young population. We investigated the relationship between obesity and renal function including proteinuria in young Japanese. METHODS: This cross-sectional study consisted of 16,031 men and 5,746 women aged from 20 to 39 years who received health examinations. The subjects were stratified into four age groups (20-24, 25-29, 30-34, and 35-39 years) or into four groups based on the number of risk factors (hypertension, hyperglycemia, dyslipidemia, and hyperuricemia). The relationship between obesity and risk factors and the relationship between obesity and estimated glomerular filtration rate (eGFR) were analyzed. RESULTS: There were no significant differences in eGFR between obese and nonobese groups, except in the male 35-39 years age group. Body mass index (BMI) in both men and women increased with increase in number of risk factors (P < 0.001). Multivariate analysis revealed that hypertension, hyperglycemia, dyslipidemia, and hyperuricemia were independently associated with obesity. Obesity and the risk factors were independently associated with proteinuria. CONCLUSION: The present study indicated that obesity was an independent risk factor for proteinuria in healthy subjects younger than 40 years of age. The other risk factors were independently associated with obesity. These findings suggest that obesity causes proteinuria concomitantly with other risk factors such as hypertension, diabetes, and dyslipidemia in young adults.

Sevelamer hydrochloride improves hyperphosphatemia in hemodialysis patients with low bone turnover rate and low intact parathyroid hormone levels.

Sevelamer improves hyperphosphatemia without increasing the calcium load. However, it remains unknown whether sevelamer restores bone metabolism in hemodialysis patients with low bone turnover osteodystrophy and hypoparathyroidism. We investigated the changes in serum intact parathyroid hormone (iPTH) and bone metabolic marker levels after replacing calcium carbonate with sevelamer in these patients. We also conducted stratified analysis based on patient background and multivariate analysis to determine the factors affecting these parameters. During sevelamer replacement therapy, serum calcium and phosphate concentrations, and the calcium phosphate product were measured at 0, 1, 3, and 6 months. Serum iPTH, bone alkaline phosphatase and osteocalcin concentrations were measured at 0 and 6 months. In hemodialysis patients (71 men and 46 women, 63 +/- 12 years old) serum calcium levels and the calcium phosphate product decreased significantly at 1 month. Serum iPTH, bone alkaline phosphatase and osteocalcin levels increased significantly at 6 months. Increases in serum iPTH concentrations were observed in all stratified groups. Significant increases in serum bone alkaline phosphatase and osteocalcin concentrations were found only in the relative hypoparathyroidism group (iPTH levels > or =51.5 pg/mL, the median pretreatment level). Multivariate analysis showed that the factors affecting change in serum iPTH level are baseline serum iPTH, baseline calcium level (> or =9.5 mg/dL), and dialysis duration of 10 years or longer. Sevelamer appears useful for the treatment of hyperphosphatemia in these patients. Particularly, in the relative hypoparathyroidism group, the iPTH secretory response is probably enhanced and bone turnover may have been improved as a result of reducing the calcium load.

Relationship between Arterial Stiffness and Blood Pressure Drop During the Sit-to-stand Test in Patients with Diabetes Mellitus.

AIM: Patients with orthostatic hypotension (OH) have high arterial stiffness. Patients with diabetes mellitus (DM) often have cardiac autonomic neuropathy that leads to OH; however, whether OH is an indicator of arterial stiffness progression is unclear. We aimed to investigate whether the cardio-ankle vascular index (CAVI) varies between DM patients with and without OH using the sit-to-stand test (STST). METHODS: One hundred and fifty-nine patients with DM underwent CAVI assessment and blood pressure (BP) and heart rate change evaluation during the STST. OH was defined as a decline in systolic BP (SBP) and/or diastolic BP of at least 20 mmHg or 10 mmHg, respectively, in the initial and late upright positions compared with that in the sitting position. RESULTS: OH was diagnosed in 42 patients (26.4%). DM patients with OH had significantly higher CAVI (9.36±1.15 versus 8.89±1.18, p=0.026) than those without OH. CAVI was significantly inversely correlated with systolic and diastolic BP changes (R=－0.347, p＜0.001 and R=－0.314, p＜0.001, respectively) in the initial upright position. Multivariate regression analysis revealed that age, SBP changes, and low frequency component in the initial upright position were independent determinants of CAVI. CONCLUSION: Patients with DM having large BP drops occurring when moving from sitting to standing have high arterial stiffness. A significant BP drop during the STST necessitates careful evaluation of advanced arterial stiffness in patient with DM.

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.

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.

Prevalence of constipation in continuous ambulatory peritoneal dialysis patients and comparison with hemodialysis patients.

Many hemodialysis patients suffer from constipation. The frequency of constipation has not been rigorously evaluated in continuous ambulatory peritoneal dialysis (CAPD) patients, however. We conducted a survey on constipation in CAPD patients and compared the findings with those in hemodialysis patients through a questionnaire. Daily dietary fiber and potassium intake were calculated from the patients' dietary records. In the questionnaire, patients were asked about bowel frequency, stool consistency, straining, and use of laxatives and resins. The frequency of constipation was 28.9% in 204 CAPD patients and 63.1% in 268 hemodialysis patients. The hemodialysis patients had a 3.14 times higher relative risk of constipation than the CAPD patients. Only 3.4% of CAPD patients needed resin to avoid hyperkalemia. Of hemodialysis patients, 49% needed resin. Among the 261 hemodialysis patients, 205 (78.5%) suppressed an urge to defecate during hemodialysis therapy. Potassium and total dietary fiber intake per day were 1.8 +/- 0.5 g and 11.0 +/- 4.0 g in CAPD patients, which were higher (P < 0.01) than the values in hemodialysis patients--1.3 +/- 0.5 g and 5.9 +/- 2.7 g. The results suggest that constipation occurs less frequently in CAPD patients than in hemodialysis patients. The low rate of constipating drug administration, dialysis modality-based lifestyle, and higher total dietary fiber intake may cause the lower prevalence of constipation in CAPD patients.

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.