ABSTRACT
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.
Subject(s)
Albuminuria/drug therapy , Benzhydryl Compounds/pharmacology , Diabetes Mellitus, Type 2/metabolism , Diabetic Nephropathies/drug therapy , Glucosides/pharmacology , Sodium, Dietary/administration & dosage , Aged , Albuminuria/metabolism , Albuminuria/urine , Blood Pressure/drug effects , Creatinine/urine , Diabetes Mellitus, Type 2/complications , Diabetic Nephropathies/etiology , Diabetic Nephropathies/metabolism , Female , Glomerular Filtration Rate/drug effects , Humans , Male , Middle Aged , Prospective StudiesABSTRACT
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.
Subject(s)
Albuminuria/drug therapy , Benzhydryl Compounds/therapeutic use , Blood Pressure/drug effects , Diabetes Mellitus, Type 2/drug therapy , Diabetic Nephropathies/drug therapy , Glucosides/therapeutic use , Kidney/drug effects , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Adult , Aged , Albuminuria/diagnosis , Albuminuria/epidemiology , Albuminuria/physiopathology , Benzhydryl Compounds/adverse effects , Biomarkers/blood , Blood Glucose/drug effects , Blood Glucose/metabolism , Blood Pressure Monitoring, Ambulatory , Circadian Rhythm , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/physiopathology , Diabetic Nephropathies/diagnosis , Diabetic Nephropathies/epidemiology , Diabetic Nephropathies/physiopathology , Female , Glomerular Filtration Rate/drug effects , Glucosides/adverse effects , Glycated Hemoglobin/metabolism , Humans , Japan/epidemiology , Kidney/physiopathology , Male , Middle Aged , Prospective Studies , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Time Factors , Treatment Outcome , Young AdultABSTRACT
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.
ABSTRACT
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.
Subject(s)
Antidiuretic Hormone Receptor Antagonists/therapeutic use , Benzazepines/therapeutic use , Diuretics/therapeutic use , Heart Failure/drug therapy , Kidney/drug effects , Renal Insufficiency, Chronic/complications , Aged , Antidiuretic Hormone Receptor Antagonists/adverse effects , Benzazepines/adverse effects , Diuresis/drug effects , Diuretics/adverse effects , Female , Heart Failure/complications , Heart Failure/diagnosis , Heart Failure/physiopathology , Humans , Kidney/physiopathology , Male , Middle Aged , Osmolar Concentration , Renal Elimination/drug effects , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/physiopathology , Retrospective Studies , Sodium/blood , Sodium/urine , Time Factors , Tolvaptan , Treatment Outcome , Urine/chemistry , Urodynamics/drug effects , Weight Loss/drug effectsABSTRACT
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=ï¼0.347, pï¼0.001 and R=ï¼0.314, pï¼0.001, 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.
Subject(s)
Autonomic Nervous System/physiopathology , Biomarkers/analysis , Blood Pressure/physiology , Diabetes Mellitus/diagnosis , Exercise Test/methods , Hypotension, Orthostatic/physiopathology , Vascular Stiffness/physiology , Adult , Carotid Intima-Media Thickness , Case-Control Studies , Cross-Sectional Studies , Diabetes Mellitus/metabolism , Female , Heart Rate , Humans , Male , Middle Aged , Postural Balance/physiology , Prognosis , Pulse Wave AnalysisABSTRACT
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.
ABSTRACT
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.
Subject(s)
Antihypertensive Agents/therapeutic use , Kidney Failure, Chronic/drug therapy , Renin-Angiotensin System/drug effects , Adolescent , Adult , Aged , Aged, 80 and over , Antihypertensive Agents/pharmacology , Creatinine/blood , Diabetic Nephropathies/blood , Disease Progression , Female , Humans , Kidney Failure, Chronic/blood , Male , Middle Aged , Potassium/blood , Regression Analysis , Retrospective Studies , Young AdultABSTRACT
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.
Subject(s)
Albuminuria/physiopathology , Blood Pressure , Circadian Rhythm/physiology , Hypoalbuminemia/physiopathology , Nephrotic Syndrome/physiopathology , Renal Insufficiency, Chronic/physiopathology , Adult , Aged , Albuminuria/blood , Autonomic Nervous System/physiopathology , Creatinine/urine , Female , Glomerular Filtration Rate , Humans , Hypoalbuminemia/urine , Male , Middle Aged , Multivariate Analysis , Nephrotic Syndrome/urine , Renal Insufficiency, Chronic/urine , Serum Albumin/metabolism , Sleep , WakefulnessABSTRACT
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.
Subject(s)
Anti-Inflammatory Agents/administration & dosage , Cyclosporine/administration & dosage , Immunosuppressive Agents/administration & dosage , Methylprednisolone/administration & dosage , Nephrosis, Lipoid/drug therapy , Adult , Anti-Inflammatory Agents/adverse effects , Drug Therapy, Combination/adverse effects , Female , Glomerular Filtration Rate , Humans , Length of Stay , Male , Methylprednisolone/adverse effects , Middle Aged , Nephrosis, Lipoid/physiopathology , Recurrence , Retrospective Studies , Severity of Illness Index , Young AdultABSTRACT
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).
Subject(s)
Antihypertensive Agents/therapeutic use , Blood Pressure/drug effects , Doxazosin/therapeutic use , Hypertension/drug therapy , Renal Insufficiency, Chronic/drug therapy , Aged , Aged, 80 and over , Blood Pressure Monitoring, Ambulatory/methods , Diabetes Mellitus , Female , Humans , Hypertension/complications , Male , Middle Aged , Posture/physiology , Prospective Studies , Renal Insufficiency, Chronic/complicationsABSTRACT
BACKGROUND: In the 'Millennium Genome Project', we identified ATP2B1 as a gene responsible for hypertension through single-nucleotide polymorphism analysis. The ATP2B1 gene encodes the plasma membrane calcium ATPase isoform 1, which contributes to the maintenance of intracellular calcium homeostasis by removing calcium ions. METHOD: Since ATP2B1 knockout mice are reported to be embryo-lethal, we generated systemic heterozygous ATP2B1 null (ATP2B1(+/-)) mice, and evaluated the implication of ATP2B1 in blood pressure. RESULTS: ATP2B1(+/-) mice revealed significantly higher SBP as measured by a radiotelemetric method. Phenylephrine-induced vasoconstriction was significantly increased in vascular rings from ATP2B1(+/-) mice, and the difference in this contraction disappeared in the presence of a nitric oxide synthase (NOS) inhibitor. Vasorelaxation to acetylcholine was significantly attenuated in vascular rings from ATP2B1(+/-) mice. In addition, cultured endothelial cells of ATP2B1(+/-) mice showed that the phosphorylation (Ser-1177) level of endothelial NOS protein was significantly lower, and nitric oxide production in endothelial cells and aorta was lower compared with those in control mice. In contrast, neural NOS expression in vascular smooth muscle cells from ATP2B1(+/-) mice and control mice were not significantly different. CONCLUSION: These results suggest that decreased ATP2B1 gene expression is associated with impaired endothelial NOS activity and nitric oxide production, and the ATP2B1 gene plays a crucial role in the regulation of blood pressure.
Subject(s)
Blood Pressure/genetics , Blood Pressure/physiology , Hypertension/genetics , Hypertension/physiopathology , Nitric Oxide/biosynthesis , Plasma Membrane Calcium-Transporting ATPases/deficiency , Plasma Membrane Calcium-Transporting ATPases/genetics , Animals , Calcium/metabolism , Calcium-Transporting ATPases/genetics , Female , Gene Expression , Heterozygote , Male , Mice , Mice, Knockout , Myocytes, Smooth Muscle/metabolism , Plasma Membrane Calcium-Transporting ATPases/physiology , Sodium-Calcium Exchanger/genetics , Vasoconstriction , VasodilationABSTRACT
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.
Subject(s)
Angiotensin II Type 1 Receptor Blockers/administration & dosage , Blood Pressure/drug effects , Calcium Channel Blockers/administration & dosage , Diuretics/administration & dosage , Hypertension/drug therapy , Adult , Aged , Dose-Response Relationship, Drug , Double-Blind Method , Drug Therapy, Combination , Female , Follow-Up Studies , Humans , Hydrochlorothiazide/administration & dosage , Hypertension/blood , Hypertension/physiopathology , Losartan/administration & dosage , Male , Middle Aged , Prospective Studies , Time Factors , Treatment Outcome , Uric Acid/blood , Young AdultABSTRACT
During hemodialysis, amino acid loss through the dialysate remained a significant problem and was not clear in some dialyzers; therefore, we investigated amino acid loss with hydrophilic and nonhydrophilic polyester-polymer alloy membranes and polyacrylonitrile membranes. Nine maintenance hemodialysis patients were studied to assess amino acid loss during hemodialysis with the three membranes. Total amino acid losses were 85.7 ± 27.2 mg/L, 83.3 ± 16.1 mg/L, and 72.1 ± 22.5 mg/L with the hydrophilic, nonhydrophilic polyester-polymer alloy, and polyacrylonitrile membranes, respectively. Amino acid losses were greater with the hydrophilic membrane compared with the polyacrylonitrile membrane for ornithine (2.0 ± 0.6 vs. 1.4 ± 0.4 mg/L, P = 0.025), phenylalanine (2.4 ± 0.9 vs. 1.8 ± 0.8 mg/L, P = 0.012), and tryptophan (0.6 ± 0.2 vs. 0.4 ± 0.2 mg/L, P = 0.023). Amino acid losses were greater with the nonhydrophilic membrane than with the polyacrylonitrile membrane for ornithine (2.0 ± 0.4 vs. 1.4 ± 0.4 mg/L, P = 0.017), phenylalanine (2.3 ± 0.5 vs. 1.8 ± 0.8 mg/L, P = 0.018), tryptophan (0.7 ± 0.2 vs. 0.4 ± 0.2 mg/L, P = 0.003), and cystine (3.2 ± 0.7 vs. 2.0 ± 0.7 mg/L, P = 0.005). In conclusion, greater losses of ornithine, phenylalanine, tryptophan, and cystine were observed with polyester-polymer alloy than with polyacrylonitrile membranes during hemodialysis. Constant attention should be paid to the amino acid loss profile to improve nutritional control in hemodialysis patients.
Subject(s)
Amino Acids/metabolism , Membranes, Artificial , Polymers/chemistry , Renal Dialysis , Acrylic Resins/chemistry , Adult , Aged , Aged, 80 and over , Alloys , Dialysis Solutions/metabolism , Female , Humans , Male , Middle Aged , Polyesters/chemistryABSTRACT
Residual renal function preservation in patients with renal failure has been shown to be related to better outcomes not only in the pre-dialysis phase but also after hemodialysis initiation. However, the effect of factors such as antihypertensive agents on residual renal function preservation has not been investigated adequately in prevalent hemodialysis patients. This study examined factors related to the rate of residual renal function preservation in 1-year hemodialysis patients who had residual renal function. We enrolled 191 consecutive maintenance hemodialysis patients who underwent hemodialysis for 1 year and maintained a urine output of more than 200 mL/day, to assess residual renal function loss. The rate of residual renal function loss was 19.9%. Multivariate analysis using residual renal function as the dependent variable revealed significant independent relationships with renin-angiotensin system inhibitor use (hazard ratio, 0.438; P = 0.027), history of cardiovascular disease (hazard ratio, 2.475; P = 0.024), and rate of weight gain between dialysis sessions (hazard ratio, 1.348; P = 0.013). No relationship was observed with calcium channel blocker use. Renin-angiotensin system inhibitor use, rate of body weight gain between dialysis sessions, and cardiovascular diseases are independently associated with residual renal function preservation in patients with residual renal function after 1 year of hemodialysis. A further intervention study is required to investigate whether treatment with renin-angiotensin system inhibitors and suppression of body weight gain preserves residual renal function for a longer time in hemodialysis patients.
Subject(s)
Antihypertensive Agents/pharmacology , Kidney Failure, Chronic/therapy , Renal Dialysis , Renin-Angiotensin System/drug effects , Adult , Aged , Aged, 80 and over , Angiotensin Receptor Antagonists/pharmacology , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Calcium Channel Blockers/pharmacology , Cardiovascular Diseases/physiopathology , Female , Follow-Up Studies , Humans , Kidney Failure, Chronic/physiopathology , Kidney Function Tests , Male , Middle Aged , Multivariate Analysis , Proportional Hazards Models , Time Factors , Weight Gain , Young AdultABSTRACT
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.
Subject(s)
Adrenergic beta-Antagonists/therapeutic use , Angiotensin Receptor Antagonists/therapeutic use , Blood Glucose/metabolism , Blood Pressure/physiology , Calcium Channel Blockers/therapeutic use , Carbazoles/therapeutic use , Diabetes Mellitus, Type 2/drug therapy , Propanolamines/therapeutic use , Renal Insufficiency, Chronic/drug therapy , Adrenergic beta-Antagonists/pharmacology , Aged , Angiotensin Receptor Antagonists/pharmacology , Antihypertensive Agents/pharmacology , Antihypertensive Agents/therapeutic use , Blood Glucose/drug effects , Blood Pressure/drug effects , Calcium Channel Blockers/pharmacology , Carbazoles/pharmacology , Carvedilol , Comorbidity , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/metabolism , Dose-Response Relationship, Drug , Female , Humans , Kidney/drug effects , Kidney/physiopathology , Male , Middle Aged , Propanolamines/pharmacology , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/physiopathology , Severity of Illness Index , Treatment OutcomeABSTRACT
We reported previously that ATP2B1 was one of the genes for hypertension receptivity in a large-scale Japanese population, which has been replicated recently in Europeans and Koreans. ATP2B1 encodes the plasma membrane calcium ATPase isoform 1, which plays a critical role in intracellular calcium homeostasis. In addition, it is suggested that ATP2B1 plays a major role in vascular smooth muscle contraction. Because the ATP2B1 knockout (KO) mouse is embryo-lethal, we generated mice with vascular smooth muscle cell-specific KO of ATP2B1 using the Cre-loxP system to clarify the relationship between ATP2B1 and hypertension. The KO mice expressed significantly lower levels of ATP2B1 mRNA and protein in the aorta compared with control mice. KO mice showed significantly higher systolic blood pressure as measured by tail-cuff method and radiotelemetric method. Similar to ATP2B1, the expression of the Na(+)-Ca(2+) exchanger isoform 1 mRNA was decreased in vascular smooth muscle cells of KO mice. However, ATP2B4 expression was increased in KO mice. The cultured vascular smooth muscle cells of KO mice showed increased intracellular calcium concentration not only in basal condition but also in phenylephrine-stimulated condition. Furthermore, phenylephrine-induced vasoconstriction was significantly increased in vascular rings of the femoral artery of KO mice. These results suggest that ATP2B1 plays important roles in the regulation of blood pressure through alteration of calcium handling and vasoconstriction in vascular smooth muscle cells.
Subject(s)
Blood Pressure/physiology , Hypertension/genetics , Hypertension/physiopathology , Muscle, Smooth, Vascular/physiopathology , Plasma Membrane Calcium-Transporting ATPases/genetics , Animals , Calcium/metabolism , Cells, Cultured , Disease Models, Animal , Femoral Artery/drug effects , Femoral Artery/physiology , Gene Deletion , Homeostasis/physiology , Mice , Mice, Knockout , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/pathology , Phenylephrine/pharmacology , Plasma Membrane Calcium-Transporting ATPases/deficiency , Vasoconstriction/drug effects , Vasoconstriction/physiologyABSTRACT
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.
Subject(s)
Amyloidosis/therapy , Blood Component Removal/methods , Renal Dialysis/adverse effects , beta 2-Microglobulin/blood , Activities of Daily Living , Adsorption , Amyloidosis/etiology , Arthralgia/etiology , C-Reactive Protein/metabolism , Equipment Design , Female , Humans , Inflammation/etiology , Inflammation/therapy , Male , Middle Aged , Pain Measurement , Quality of Life , Time Factors , Treatment OutcomeABSTRACT
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.
Subject(s)
Brain Infarction/complications , Kidney Diseases/etiology , Kidney Diseases/physiopathology , Adult , Aged , Aged, 80 and over , Chronic Disease , Disease Progression , Female , Humans , Male , Middle Aged , Prognosis , Prospective Studies , Time FactorsABSTRACT
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.