Gen Yasuda

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 ≥60 mL/min/1.73 m2: 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.

Silent Brain Infarction and Rapid Decline of Kidney Function in Patients With CKD: A Prospective Cohort Study

BACKGROUNDnSeveral 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.nnnSTUDY DESIGNnProspective cohort study.nnnSETTING & PARTICIPANTSn142 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.nnnPREDICTORnSBI.nnnOUTCOMESnComposite 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.nnnMEASUREMENTSnBrain magnetic resonance imaging was performed to determine the presence or absence of SBI.nnnRESULTSnAt 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).nnnLIMITATIONSnStudy size was small.nnnCONCLUSIONnWe 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.

Effect of renin-angiotensin system inhibitor on residual glomerular filtration rate in hemodialysis patients.

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 1xa0year and maintained a urine output of more than 200xa0mL/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; Pxa0=xa00.027), history of cardiovascular disease (hazard ratio, 2.475; Pxa0=xa00.024), and rate of weight gain between dialysis sessions (hazard ratio, 1.348; Pxa0=xa00.013). 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 1xa0year 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.

Long‐Term Efficacy and Safety of the Small‐Sized β2‐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. β2‐microglobulin (β2‐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 β2‐m from the circulating blood of patients with dialysis‐related amyloidosis. Using a minimum type of β2‐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 years treatment with the S‐15 column, the β2‐m level decreased from 29.3u2003±u20039.6u2003mg/L to 24.7u2003±u20035.1u2003mg/L (Pu2003<u20030.05), and the high sensitive C‐reactive protein level decreased from 2996u2003±u20034380u2003ng/mL to 1292u2003±u20031774u2003ng/mL. After one year of S‐15 column use, pinch strength increased from 5.9u2003±u20033.0u2003pounds to 7.2u2003±u20033.2u2003pounds (Pu2003<u20030.05), 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.

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

Abstract 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) (nu2009=u200999) and LST–amlodipine (AML) (nu2009=u200977) 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 (<5.6u2009mg/dL) but not in patients with high baseline SUA.

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 cardioankle 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.

Loss of amino acids into dialysate during hemodialysis using hydrophilic and nonhydrophilic polyester-polymer alloy and polyacrylonitrile membrane dialyzers.

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 85.7u2009±u200927.2u2009mg/L, 83.3u2009±u200916.1u2009mg/L, and 72.1u2009±u200922.5u2009mg/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 (2.0u2009±u20090.6 vs. 1.4u2009±u20090.4u2009mg/L, Pu2009=u20090.025), phenylalanine (2.4u2009±u20090.9 vs. 1.8u2009±u20090.8u2009mg/L, Pu2009=u20090.012), and tryptophan (0.6u2009±u20090.2 vs. 0.4u2009±u20090.2u2009mg/L, Pu2009=u20090.023). Amino acid losses were greater with the nonhydrophilic membrane than with the polyacrylonitrile membrane for ornithine (2.0u2009±u20090.4 vs. 1.4u2009±u20090.4u2009mg/L, Pu2009=u20090.017), phenylalanine (2.3u2009±u20090.5 vs. 1.8u2009±u20090.8u2009mg/L, Pu2009=u20090.018), tryptophan (0.7u2009±u20090.2 vs. 0.4u2009±u20090.2u2009mg/L, Pu2009=u20090.003), and cystine (3.2u2009±u20090.7 vs. 2.0u2009±u20090.7u2009mg/L, Pu2009=u20090.005). 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.

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

BackgroundCyclosporine 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.MethodsForty-six adult patients with biopsy-proven MCNS were analyzed retrospectively. This study included three groups. Group 1 (nxa0=xa017) was treated with intravenous MPT (0.5 or 1.0xa0g/day for 3xa0days) followed by oral cyclosporine (2–3xa0mg/kg/day) and prednisolone (30xa0mg/day). Group 2 (nxa0=xa015) was treated with intravenous MPT followed by oral prednisolone (0.4–0.8xa0mg/kg/day). Group 3 (nxa0=xa014) was treated with oral prednisolone (0.6–1.0xa0mg/kg/day) alone.ResultsThe length of hospital stay was the shortest in Group 1 (Pxa0<xa00.001). The mean duration to achieve <20xa0mg/day of prednisolone was also the shortest in Group 1 (Pxa0<xa00.05). Complete remission rates were 100xa0% in Group 1, 85.7xa0% in Group 2, and 69.2xa0% in Group 3 during the 9-month follow-up (Pxa0=xa00.073). The rate of adverse effects caused by prednisolone was less in Group 1 (Pxa0<xa00.05). Multivariate analysis revealed that the independent determinants of durations of remission were the selectivity index (Pxa0=xa00.004), eGFR (Pxa0=xa00.001) and the use of cyclosporine (Pxa0=xa00.045).ConclusionsCombination therapy with cyclosporine may be a beneficial treatment option for new-onset MCNS in adults because of its clinical efficacy and safety.

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

BackgroundTolvaptan, 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).MethodsWe 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.ResultsTolvaptan decreased the body weight and increased the urine volume (pu2009=u20090.001). The urine osmolality significantly decreased throughout the study period. Urinary Na/Cr ratio and FENa changed significantly after 4xa0h, and more remarkable after 8xa0h (pu2009=u20090.003, both). Serum creatinine increased slightly after 1xa0week of treatment (pu2009=u20090.012). The alteration of body weight within the study period correlated negatively with the baseline urine osmolality (ru2009=u2009−0.479, pu2009=u20090.038), the baseline urine volume (ru2009=u2009−0.48, pu2009=u20090.028), and the baseline inferior vena cava diameter (IVCD) (ru2009=u2009−0.622, pu2009=u20090.017). Hyponatremia was improved to the normal value, and the augmentations of the sodium concentration were negatively associated with the basal sodium levels (pu2009=u20090.01, ru2009=u2009−0.546).ConclusionsTolvaptan 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.

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

ABSTRACT 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.