Toshiki Kutsuna

Habitual Physical Activity Measured by Accelerometer and Survival in Maintenance Hemodialysis Patients

BACKGROUND AND OBJECTIVES The association between mortality and physical activity based on self-report questionnaire in hemodialysis patients has been reported previously. However, because self-report is a subjective assessment, evaluating true physical activity is difficult. This study investigated the prognostic significance of habitual physical activity on 7-year survival in a cohort of clinically stable and adequately dialyzed patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A total of 202 Japanese outpatients who were undergoing maintenance hemodialysis three times per week at the hemodialysis center of Sagami Junkanki Clinic (Japan) from October 2002 to February 2012 were followed for up to 7 years. Physical activity was evaluated using an accelerometer at study entry and is expressed as the amount of time a patient engaged in physical activity on nondialysis days. Cox proportional hazard regression was used to assess the contribution of habitual physical activity to all-cause mortality. RESULTS The median patient age was 64 (25th, 75th percentiles, 57, 72) years, 52.0% of the patients were women, and the median time on hemodialysis was 40.0 (25th, 75th percentiles, 16.8, 119.3) months at baseline. During a median follow-up of 45 months, 34 patients died. On multivariable analysis, the hazard ratio for all-cause mortality per 10 min/d increase in physical activity was 0.78 (95% confidence interval, 0.66-0.92; P=0.002). CONCLUSIONS Engaging in habitual physical activity among outpatients undergoing maintenance hemodialysis was associated with decreased mortality risk.

Relationship Between Lower Extremity Muscle Strength and All-Cause Mortality in Japanese Patients Undergoing Dialysis

Background Skeletal muscle wasting is common and insidious in patients who are undergoing hemodialysis. However, the association between lower extremity muscle strength and all-cause mortality remains unclear in this population. Objective The purpose of this study was to investigate the prognostic significance of lower extremity muscle strength on 7-year survival in a cohort of patients who were clinically stable and undergoing hemodialysis. Design A prospective cohort study was conducted. Methods A total of 190 Japanese outpatients who were undergoing maintenance hemodialysis 3 times per week at a hemodialysis center were followed for up to 7 years. Lower extremity muscle strength was evaluated using a handheld dynamometer at the time of patient enrollment in the study. Muscle strength data were divided by dry weight and expressed as a percentage. A Cox proportional hazards regression model was used to assess the contribution of lower extremity muscle strength to all-cause mortality. Results The median age (25th and 75th percentiles) of this study population was 64 years (57 and 72 years), 53.2% of the patients were women, and the time on hemodialysis was 39.0 months (15.9 and 110.5 months) at baseline. During a median follow-up of 36.0 months, there were 30 deaths. With a multivariate Cox model, the hazard ratio in the group with a knee extensor strength of <40% was 2.73 (95% confidence interval=1.14–6.52) compared with that in the ≥40% group. Limitations This was a small-scale observational study, and the mechanisms underlying the higher mortality risk in patients with poor muscle strength undergoing hemodialysis than in other patients undergoing hemodialysis remain to be elucidated. Conclusions Decreased lower extremity muscle strength was strongly associated with increased mortality risk in patients undergoing hemodialysis.

Physical Activity Is Necessary to Prevent Deterioration of the Walking Ability of Patients Undergoing Maintenance Hemodialysis

Maintenance of the walking ability is very important for smooth continuation of maintenance hemodialysis (HD). The aim of the present study was to clarify the physical activity level in daily living that HD patients should maintain to prevent deterioration of their walking ability. Outpatients undergoing maintenance HD, consisting of 65 males and 88 females with a mean age of 64 ± 11 years, were recruited for the present study. Their physical activity level was recorded over a week with an accelerometer. The physical activity level in daily living was defined as the sum of the lengths of time for which the patients were engaged in physical activity of light or greater intensity during the day, and expressed as the average duration per day. The walking ability was assessed by the normal walking speed and maximum walking speed. Data were analyzed using the receiver operating characteristic (ROC) curve, and the cut‐off point for the physical activity time was determined to predict deterioration of the walking ability. In the prediction of deterioration of the normal and maximum walking speeds, the areas under the ROC curve for the physical activity time were 0.78 (95% confidence interval, 0.69–0.87, P < 0.001) and 0.75 (95% confidence interval, 0.63–0.86, P < 0.001), respectively. Moreover, the ROC curve revealed that the cut‐off point for the physical activity time to prevent deterioration of the normal and maximum walking speeds was 50 min/day. Thus, HD patients should engage in physical activity for at least 50 min/day to prevent deterioration of their walking ability.

Excessive Fall of Blood Pressure During Maintenance Hemodialysis in Patients With Chronic Renal Failure Is Induced by Vascular Malfunction and Imbalance of Autonomic Nervous Activity

Acute hypotension during maintenance hemodialysis (HD) is not only a critical complication, but also an independent risk factor for mortality in patients with chronic renal failure (CRF). This study was designed to clarify the mechanisms underlying excessive fall of blood pressure during HD. Fifty‐six CRF patients with HD thrice a week were divided into two groups according to the intradialytic hypotension episodes after 4 weeks of the observation period; the hypotension group, showing four or more episodes of intradialytic hypotension, and the non‐hypotension group, showing three episodes of intradialytic hypotension or less. The intradialytic hypotension was defined as a fall of ≥30 mm Hg in the systolic blood pressure during HD. The brachial‐ankle pulse wave velocity (ba‐PWV), serum high‐sensitivity (hs)‐CRP, reactive oxygen species (ROS) generation, and serum malondialdehyde‐modified LDL (MDA‐LDL) were measured before HD. The high‐ frequency (HF) and low‐frequency components (LF) of the heart rate variability and entropy were analyzed by the maximal entropy method. The ba‐PWV, hs‐CRP, ROS generation, and MDA‐LDL were significantly higher in the hypotension group than in the non‐hypotension group. HF, LF/HF, and entropy during HD increased significantly in the non‐hypotension group, while entropy during HD decreased significantly in the hypotension group as compared with the baseline. LF/HF and entropy during HD were significantly lower in the hypotension group than in the non‐hypotension group. These findings suggest that the major factors causing excessive fall of blood pressure during HD in patients with CRF might be vascular malfunction and imbalance of autonomic nervous activity.

Beneficial Effects of L‐ and N‐type Calcium Channel Blocker on Glucose and Lipid Metabolism and Renal Function in Patients with Hypertension and Type II Diabetes Mellitus

It has been proved that cilnidipine has N-type calcium channels inhibitory activity as well as L-type calcium channels and inhibits excessive release of norepinephrine from the sympathetic nerve ending. This study was undertaken to compare the efficacy of amlodipine (an inhibitor of L-type calcium channels) and cilnidipine (an inhibitor of both L-type and N-type calcium channels) in patients with hypertension and type II diabetes mellitus. Seventy-seven hypertensive patients were divided into two groups according to presence/absence of type II diabetes mellitus. In these two groups of patients, the effects of amlodipine and cilnidipine on glucose and lipid metabolism and renal function were compared. As for glucose and lipid metabolism, homeostasis model assessment insulin resistance (HOMA-R) level in the non-diabetic group and triglyceride in the diabetes group were significantly lower with cilnidipine than with amlodipine. As regards renal function in the diabetic group, estimated glomerular filtration rate (eGFR) was significantly higher and urinary albumin/creatinine ratio was significantly lower with cilnidipine than with amlodipine. Cilnidipine which inhibits N-type calcium channels is more useful for patients with hypertension and diabetes mellitus from its effects on glucose and lipid metabolism and renal function.

Association of Habitual Physical Activity Measured by an Accelerometer with High-Density Lipoprotein Cholesterol Levels in Maintenance Hemodialysis Patients

After confirming the relationship between high-density lipoprotein cholesterol (HDL-C) levels and mortality in hemodialysis patients for study 1, we investigated the effect of physical activity on their HDL-C levels for study 2. In study 1, 266 hemodialysis patients were monitored prospectively for five years, and Cox proportional hazard regression confirmed the contribution of HDL-C to mortality. In study 2, 116 patients were recruited after excluding those with severe comorbidities or requiring assistance from another person to walk. Baseline characteristics, such as demographic factors, physical constitution, primary kidney disease, comorbid conditions, smoking habits, drug use, and laboratory parameters, were collected from patient hospital records. An accelerometer measured physical activity as the number of steps per day over five consecutive days, and multiple regression evaluated the association between physical activity and HDL-C levels. Seventy-seven patients died during the follow-up period. In study 1, we confirmed that HDL-C level was a significant predictor of mortality (P = 0.03). After adjusting for patient characteristics in study 2, physical activity was independently associated with HDL-C levels (adjusted R 2 = 0.255; P = 0.005). In conclusion, physical inactivity was strongly associated with decreased HDL-C levels in hemodialysis patients.

Determinants of Slow Walking Speed in Ambulatory Patients Undergoing Maintenance Hemodialysis

Walking ability is significantly lower in hemodialysis patients compared to healthy people. Decreased walking ability characterized by slow walking speed is associated with adverse clinical events, but determinants of decreased walking speed in hemodialysis patients are unknown. The purpose of this study was to identify factors associated with slow walking speed in ambulatory hemodialysis patients. Subjects were 122 outpatients (64 men, 58 women; mean age, 68 years) undergoing hemodialysis. Clinical characteristics including comorbidities, motor function (strength, flexibility, and balance), and maximum walking speed (MWS) were measured and compared across sex-specific tertiles of MWS. Univariate and multivariate logistic regression analyses were performed to examine whether clinical characteristics and motor function could discriminate between the lowest, middle, and highest tertiles of MWS. Significant and common factors that discriminated the lowest and highest tertiles of MWS from other categories were presence of cardiac disease (lowest: odds ratio [OR] = 3.33, 95% confidence interval [CI] = 1.26–8.83, P<0.05; highest: OR = 2.84, 95% CI = 1.18–6.84, P<0.05), leg strength (OR = 0.62, 95% CI = 0.40–0.95, P<0.05; OR = 0.57, 95% CI = 0.39–0.82, P<0.01), and standing balance (OR = 0.76, 95% CI = 0.63–0.92, P<0.01; OR = 0.81, 95% CI = 0.68–0.97, P<0.05). History of fracture (OR = 3.35, 95% CI = 1.08–10.38; P<0.05) was a significant factor only in the lowest tertile. Cardiac disease, history of fracture, decreased leg strength, and poor standing balance were independently associated with slow walking speed in ambulatory hemodialysis patients. These findings provide useful data for planning effective therapeutic regimens to prevent decreases in walking ability in ambulatory hemodialysis patients.

Development of a novel questionnaire evaluating disability in activities of daily living in the upper extremities of patients undergoing maintenance hemodialysis

The aim of the present study was to develop a novel questionnaire evaluating disability in the activities of daily living in the upper extremities of hemodialysis (HD) patients (QDUE‐HD). We recruited 83 patients (40 males and 43 females) aged 66 ± 8 years, and measured their muscle strength and range of motion in the upper extremities. Moreover, 14 patients performed a six‐week exercise training regimen (the exercise group) and were compared with 15 patients not performing such training (the control group). In an initial questionnaire consisting of 37 items, 30 were taken from the Disabilities of the Arm, Shoulder and Hand questionnaire and the Activities of Daily Living Test, and the remaining seven were selected from activities that HD patients perceived as impossible or extremely difficult to perform. The principal factor analysis focused on 11 items, as 26 showing floor and ceiling effects were excluded. These 11 items were divided into two categories consisting of six items termed “light work” and five termed “holding activities”. The scores for light work and holding activities correlated significantly and positively with both muscle strength and range of motion in the upper extremities. These scores increased significantly after the six‐week exercise training as compared with those before training in the exercise group. We conclude that the QDUE‐HD is clinically useful for evaluating disability in activities of daily living in the upper extremities of HD patients because of its high reliability, validity and responsiveness.

Effects of prolonged expiration breathing on cardiopulmonary responses during incremental exercise

This study was designed to clarify the effects of breathing with prolonged expiration on cardiopulmonary responses and autonomic nervous activity during incremental exercise. Eleven healthy men were randomly assigned to breathing mode: a prolonged expiration breathing with a 2-s inspired time and 4-s expired time and a spontaneous breathing without any constraints. Oxygen uptake (V(O2)), ventilation efficiency (V(E)/V(CO2)) and rate pressure product were measured. Low- (LF) and high-frequency (HF) components of blood pressure and heart rate variability were analyzed to assess sympathetic and parasympathetic nervous activities, respectively. V(E)/V(CO2), rate pressure product and LF were significantly lower, and [Formula: see text] and HF were significantly higher during exercise with prolonged expiration than with spontaneous breathing. Striking effects of prolonged expiration breathing included the improvement of ventilation efficiency, the suppression of sympathetic nervous activity and the activation of parasympathetic one during incremental exercise. Furthermore, prolonged expiration breathing may have suppressed the exercise-induced increase in myocardial V(O2).

Endothelial Dysfunction Is Associated with Cognitive Impairment of Elderly Cardiovascular Disease Patients: A Reactive Hyperemia-Peripheral Arterial Tonometry Study

Cognitive impairment is frequently represented in elderly patients with cardiovascular disease (CVD); yet, the mechanism is uncertain. Recent studies have suggested the association between the vascular endothelial dysfunction and cognitive impairment. The aim of this study was to clarify the association between endothelial dysfunction and cognitive impairment in elderly patients with CVD.A total of 80 elderly patients (> 70 years old) with CVD were included. Patients who had already pharmacologically intervened for cognitive impairment were excluded. The endothelial dysfunction was assessed by the reactive hyperemia-peripheral arterial tonometry (RH-PAT). Cognitive impairment was diagnosed by the Mini-mental state examination.The RH-PAT index was significantly lower in cognitive impairment (median 1.60 [interquartile range (IQR) 1.34 to 1.89], n = 51) as compared with non-cognitive impairment (median 1.75 [IQR 1.55 to 2.30], n = 29, P = 0.005). By a multivariate analysis, the RH-PAT index was independently associated with cognitive impairment (odds ratio: 0.89; 95% confidence interval: 0.81 to 0.97; per 0.1, P = 0.044). In the receiver-operating characteristic analysis, the best cut-off of the RH-PAT index to identify cognitive impairment was 1.65 (area under the curve 0.67; P = 0.011) with limited the sensitivity (63%) and specificity (66%).A lower RH-PAT index was significantly associated with the presence of cognitive impairment in elderly CVD patients. Further studies are required to clarify the mechanism and the causal relationship between the endothelial dysfunction and cognitive impairment in patients with CVD.