Effects of diet and exercise on adipocytokine levels in patients with moderate to severe chronic kidney disease.

BACKGROUND AND AIMS: Obesity is a pro-inflammatory risk factor for progression of CKD and cardiovascular disease. We hypothesized that implementation of caloric restriction and endurance exercise would improve adipocytokine profiles in patients with moderate to severe CKD. METHODS AND RESULTS: We enrolled patients with moderate to severe CKD through a multi-center pilot randomized trial of diet and exercise in a 4-arm design (dietary restriction of 10%-15% reduction in caloric intake, exercise three times/week, combined diet and exercise, and control) (NCT01150851). Adipocytokines (adiponectin and leptin) were measured at the beginning and end of the study period as secondary outcomes. Treatment effect was analyzed in a multivariable model adjusted for baseline outcome values, age, gender, site and diabetes. A total of 122 participants were consented, 111 were randomized (42% female, 25% diabetic, and 91% hypertensive), 104 started intervention and 92 completed the study (Figure 1). Plasma adiponectin levels increased significantly in response to diet by 23% (95% CI: 0.2%, 49.8%, p = 0.048) among participants randomized to the caloric restriction and usual activity arm but not to exercise, whereas circulating leptin did not change by either treatment. CONCLUSION: Our data suggest that dietary caloric restriction increases plasma adiponectin levels in stage 3-4 CKD patients, with limited effect on leptin levels. These findings suggest the potential for improving the metabolic milieu of CKD with moderate calorie restriction.

Metabolic Effects of Diet and Exercise in Patients with Moderate to Severe CKD: A Randomized Clinical Trial.

CKD is steadily increasing along with obesity worldwide. Furthermore, obesity is a proinflammatory risk factor for progression of CKD and cardiovascular disease. We tested the hypothesis that implementation of caloric restriction and aerobic exercise is feasible and can improve the proinflammatory metabolic milieu in patients with moderate to severe CKD through a pilot, randomized, 2×2 factorial design trial. Of 122 participants consented, 111 were randomized to receive caloric restriction and aerobic exercise, caloric restriction alone, aerobic exercise alone, or usual care. Of those randomized, 42% were women, 25% were diabetic, and 91% were hypertensive; 104 started intervention, and 92 completed the 4-month study. Primary outcomes were a change from baseline in absolute fat mass, body weight, plasma F2-isoprostane concentrations, and peak oxygen uptake (VO2 peak). Compared with usual care, the combined intervention led to statistically significant decreases in body weight and body fat percentage. Caloric restriction alone also led to significant decreases in these measures, but aerobic exercise alone did not. The combined intervention and each independent intervention also led to significant decreases in F2-isoprostane and IL-6 concentrations. No intervention produced significant changes in VO2 peak, kidney function, or urine albumin-to-creatinine ratio. In conclusion, 4-month dietary calorie restriction and aerobic exercise had significant, albeit clinically modest, benefits on body weight, fat mass, and markers of oxidative stress and inflammatory response in patients with moderate to severe CKD. These results suggest healthy lifestyle interventions as a nonpharmacologic strategy to improve markers of metabolic health in these patients.

Supervised Exercise Intervention and Overall Activity in CKD.

INTRODUCTION: Patients are often instructed to engage in multiple weekly sessions of exercise to increase physical activity. We aimed to determine whether assignment to a supervised exercise regimen increases overall weekly activity in individuals with chronic kidney disease (CKD). METHODS: We performed a secondary analysis of a pilot randomized 2 × 2 factorial design trial examining the effects of diet and exercise (10%-15% reduction in caloric intake, 3 supervised exercise sessions/wk, combined diet restriction/exercise, and control). Activity was measured as counts detected by accelerometer. Counts data were collected on all days for which an accelerometer was worn at baseline, month 2, and month 4 follow-up. The primary outcome was a relative change from baseline in log-transformed counts/min. Generalized estimating equations were used to compare the primary outcome in individuals in the exercise group and the nonexercise group. RESULTS: We examined 111 individuals randomized to aerobic exercise or usual activity (n = 48 in the exercise group and n = 44 controls). The mean age was 57 years, 42% were female, and 28% were black. Median overall adherence over all time was 73%. Median (25th, 75th percentile) counts/min over nonsupervised exercise days at months 2 and 4 were 237.5 (6.5, 444.4) for controls and 250.9 (7.7, 529.8) for the exercise group (P = 0.74). No difference was observed in the change in counts/min between the exercise and control groups over 3 time points (ß [fold change], 0.96, 95% confidence interval [CI], 0.91, 1.02). CONCLUSION: Engaging in a supervised exercise program does not increase overall weekly physical activity in individuals with stage 3 to 4 CKD.

Immediate blood pressure-lowering effects of aerobic exercise among patients with chronic kidney disease.

AIM: The current study was designed to determine the effect of moderate-intensity aerobic exercise on blood pressure responses within the laboratory for 60 min post exercise and in the subsequent 24 h period in patients with chronic kidney disease. METHODS: Twenty-four subjects with stages 2-4 chronic kidney disease (age = 54.5 +/- 15.2 years, body mass index = 32.0 +/- 5.9 kg/m(2)) on antihypertensive medication completed this study. In random counterbalanced order, subjects were asked to either walk for 40 min at 50-60% VO(2peak) (oxygen consumption) or, on a separate day, to sit quietly in the laboratory for the same length of time. Following exercise or the non-exercise period, blood pressure was taken at 10 min intervals for 60 min. Subjects then wore an ambulatory blood pressure monitor for the next 24 h. RESULTS: Systolic blood pressure (mmHg) was reduced by 6.5 +/- 10.8 compared with the pre-exercise baseline value (130.3 +/- 21.1) in the laboratory after exercise and this was greater than after the control period (0.73 +/- 10.3, P < 0.05). Diastolic blood pressure (mmHg) was reduced following exercise (2.5 +/- 6.4) compared with the control period (2.1 +/- 4.9, P < 0.05). The mean 24 h readings did not differ between exercise or non-exercise days. CONCLUSION: Acute aerobic exercise leads to reduced blood pressure for at least 60 min within the laboratory in chronic kidney disease patients.

Preservation of fat-free mass after two distinct weight loss diets with and without progressive resistance exercise.

BACKGROUND: Preserving fat-free mass (FFM) during weight loss is important in older adults. The purpose was to examine a low-fat diet (LFD) versus a carbohydrate-restricted diet (CRD) with and without progressive resistance exercise (PRE) on preservation of FFM in older men with metabolic syndrome. METHODS: A total of 42 men (59±7 years) were matched [body mass index (BMI)] and randomized to LFD, LFD&PRE, CRD, and CRD&PRE. PRE groups performed supervised strength training three times per week. Body weight, composition, metabolic syndrome criteria, and strength were measured at baseline and week 12. A 3-day diet record was kept at baseline and at weeks 1, 6, and 12. RESULTS: Attrition (24%) was similar between groups. Depicted as % carbohydrate:fat:protein, the intervention diet was: LFD=55:24:18, LFD&PRE=57:20:20, CRD=16:54:28, and CRD&PRE=12:56:31. Weight (lb) decreased similarly in all groups (LFD, -18.0±7.4; LFD&PRE, -19.8±12.8; CRD, -20.2±8.0; CRD&PRE, -22.7±6.0; P<0.001), and number of participants with metabolic syndrome decreased in all groups (-3, -6, -3, -4, respectively). Percent of weight loss from appendicular FFM was 27.5%, 15.9%, 15.7%, and 17.3% respectively. A trend was found when comparing LFD and LFD&PRE (P=0.068), and when comparing LFD&CRD (P=0.072). Triglycerides improved more for the LFD&PRE, CRD, and CRD&PRE groups compared to the LFD group (P<0.05). Improvements in high-density lipoprotein-cholesterol were better in the CRD&PRE group (4.1±5.1 mg/dL) versus the LFD group (-5.0±5.9 mg/dL; P<0.01). CONCLUSIONS: LFD&PRE, CRD, and CRD&PRE preserve FFM similarly. PRE is an important component of a LFD during weight loss in this population.

Lack of circulating bioactive and immunoreactive IGF-I changes despite improved fitness in chronic kidney disease patients following 48 weeks of physical training.

OBJECTIVE: As known abnormalities exist in the insulin-like growth factor (IGF) system in chronic kidney disease (CKD) patients, the measurement of bioactive IGF-I may provide further insight into the therapeutic potential of long-term exercise training. DESIGN: Patients (N=21) with stages 3 and 4 CKD were recruited from a local nephrology practice in Springfield, MA and randomized into matched treatment and control groups. The treatment group participated in 48 weeks of supervised, progressive exercise training and dietary counseling, while the control group received only usual care. Treadmill testing, anthropometric measurements, and blood samples for analysis of immunoreactive IGF-I, IGF-II, IGFBP-1 and -2, and bioactive IGF-I were taken at baseline, 24 weeks, and 48 weeks. RESULTS: There were no significant differences in any of the components of the IGF system (all p-values>0.05). Immunoreactive IGF-I levels correlated significantly with bioactive IGF-I at baseline (r=0.50, p=0.02) and at 48 weeks (r=0.64, p=0.01). There was a significant interaction between group and time for both VO(2peak) (p=0.03) and total treadmill time (TT) (p<0.01). CONCLUSIONS: Despite improvements in physical performance, a 48-week training program did not affect any of the circulating IGF system measurements. Disparities between these findings and those of other researchers reporting a biphasic response to long-term training may be explained by differences in study groups and exercise programs.