Title:
The impact of body weight management in chronic kidney disease patients with obesity
Running head:
BW management in obese CKD patients Abstract
Objective: Chronic kidney disease (CKD) and obesity are important public health concerns. As obesity may initiate and/or accelerate kidney damage, weight control may benefit CKD patients.
Design and Methods: We examined the influence of dietary management and physical exercise in 38 obese CKD patients with or without target reduction of body weight (BW)≥3% from baseline.
Results: After a 2-month lifestyle intervention program, those with target BW control had significant improvement of blood pressure (BP) control, as well as reduced lipid profiles, serum creatinine level (1.1±0.3 vs. 0.8±0.3; P<0.001), estimated glomerular filtration rate (75.9±21.2 vs. 104.9±38.1; P < 0.001), and proteinuria (76.3% vs. 50.0%; P=0.02). They had greater improvement in cardiorespiratory endurance in an 800-meter running test (375.1±64.7 vs. 327.1±84.0 sec; P=0.001), better abdominal muscle strength and endurance in a timed sit-up test (13.6±9.1 vs. 19.9±9.2 number/min; P=0.005), and greater flexibility in a sit and reach test (18.8±10.9 vs. 27.8±10.9 cm; P<0.001) comparing baseline and post-intervention values.
Conclusions: A combination of dietary management and exercise were associated with improvements in health-related physical fitness, cardiovascular risk factors (BP and lipid control) and renal profiles in obese CKD patients. Supportive individualized programs for lifestyle change could exert beneficial effects, but long-term research with a larger patient population is needed to elucidate the optimal effective
Introduction
The worldwide prevalence of obesity has increased steadily in recent decades, a trend that has been linked to increased dietary intake, a Western diet, and a sedentary lifestyle, and has become an important public health issue [1]. The prevalence of overweight and obesity has increased from 10.5% up to 38.4% in the general population in Taiwan according to surveys conducted in 1993-1996 and 2008-2010, respectively [2,3]. Numerous medical problems have been reported in association with obesity, including hypertension, proteinuria, and a predisposition to certain forms of renal disease. In 1974, nephrotic-range proteinuria in obese individuals was reported for the first time [4]. Subsequently, several studies reported glomerulomegaly, focal glomerulosclerosis, mesangial hyperplasia and minimal foot process fusion in renal biopsy in morbidly obese patients [5-7]. This occurs at the expense of increased intracapillary pressures [8] and may be especially risky in adults with a decreased nephron number [9]. Obesity may initiate and/or accelerate kidney damage, and has been associated with increased mortality [10].
Obese or overweight patients should regularly consult a dietitian, and should be educated with regard to adequate daily protein intake and caloric intake to reduce their body weight. Moreover, these measures must be implemented in combination with increased physical exercise (30 min/day). Body weight management could reduce proteinuria by 30% [11], decrease metabolic demands on the kidney, and may delay the progression of CKD [12].
In this study, we demonstrated that body weight reduction through a combination of diet control and exercise could improve the renal profile, lipid profile, blood pressure control, and exercise tolerance of obese CKD patients.
Methods and Procedures Patients
Sixty patients were screened and deemed eligible to enter this study, but 15 of them declined to participate. We enrolled 45 patients with chronic kidney disease (CKD) stages 1 to 3 from the outpatient department of a medical center (VGHTC) in central Taiwan. All patients met the following inclusion criteria: (1) 20 to 60 years of age; (2) CKD stage 1-3; (3) overweight or obese with body mass index (BMI) more than 24 kg/m2; (4) written informed consent to participate in the study was obtained after the
purpose and nature of the investigation had been clearly explained to the patients. The exclusion criteria were as follows: (1) evidence of liver dysfunction as determined by any one of the following: serum glutamic-pyruvic transaminase (GPT) value exceeding 2 times the upper limit of normal value (10-35 IU/L) at visit, a history of liver cirrhosis, hepatic encephalopathy, or esophageal or gastric varices; (2) predicted survival less than one year; (3) difficulty performing physical exercise; (3) recent myocardial infarction, stroke or transient ischemic attack; (4) intractable hypertension. The target body weight reduction was more than 3% from the baseline. The patients’demographic characteristics and clinical data were collected before and after the 8-week body weight control intervention and analyzed. Approval for the study was obtained from the institutional review board of the hospital (TCVGH), and all patients gave written informed consent (CE11183) before entering the study. Body weight management
A tailored lifestyle intervention program was implemented and patients' medication regimens remained unchanged throughout the study period. During the program patients were encouraged to increase their level of physical exercise (30 min/day in 5 out of 7 weekdays), were strongly recommended to modify their daily habits to increase activity levels (walking rather than using mechanized transport or the elevator, when possible) as well as regular consultations with a dietitian who provided patients with a diet plan designed to provide energy intake no higher than
25/kcal/kg/ideal body weight/day, with 55% of calories coming from carbohydrates and total fat not exceeding 30% of calories (fatty acids <10% of calories and dietary cholesterol limited to 300 mg/day), according to guidelines of the American Heart Association Step One Diet. Protein intake was restricted to 0.8 gm/kg of ideal body weight/day. Patients were prescribed low-salt food (meal containing <1.8 g/day of sodium). All patients were required to attend a course for three hours a week in which they received instruction pertaining to body weight control in chronic kidney disease patients and to keep a daily diet diary during the entire 8-week course. During the course the concept of CKD and obesity, self-measuring of calories and dietary composition in food, choosing food, cooking, and body weight control skills were explained.
Laboratory measurements
Blood samples from venous blood were collected in the morning between 8:00 a.m. and 9:00 a.m. after an overnight fast and 2 hours after meal from all patients at baseline and again at the end of the 8-week intervention. All assays were analyzed in the central laboratory immediately. After clot formation, the samples were centrifuged (4,000 rpm) at room temperature for 10 min and the serum was subjected to other biochemical studies. In all patients, we measured fasting and post-prandial serum glucose (FBS and PC), low-density and high-density lipoprotein cholesterol (LDL-C and HDL-C), total cholesterol (Chol), triglyceride (TG), albumin (Alb), blood urea nitrogen (BUN), creatinine (Cr), and estimated glomerular filtration rate (eGFR). Hematuria was defined as more than 5 red blood cells per high-power field by two successive microscopic examinations of the urine. Proteinuria was defined as a protein to Cr ratio of more than 0.2 mg/mg.
Body Composition Measurements
Medical, Kyoungsan, Korea) at baseline and at the end of the 8-week intervention. A trained nurse measured each subject’s body composition on the machine, which was connected to a computer where the data was automatically stored. The results were then printed out.
Physical exercise training and education
To determine blood pressure (BP) at baseline, 3 consecutive BP readings after patients had rested for 10 minutes in the sitting position were done and the average was calculated. For one hour a week during the 8-week period, the patients received instruction on physical exercise training, which included walking, jogging, skipping rope, aerobics classes, yoga, and stretching. The quality and quantity of the training exercises were evaluated for each patient and included: cardiorespiratory endurance (run 800 meters), abdominal muscle strength and endurance (timed sit-ups, number/min), and flexibility training for the lower back (sit and reach, cm). Patients were taught how to do aerobic exercise and muscle strength training during the intervention program, and were required to perform physical exercise for 30 min/day at home.
Statistical Analyses
Data management and statistical analysis were performed using the SPSS statistical software program (version 12). The t test and Wilcoxon Signed-Rank test were used for comparisons between before and after the body weight control intervention program. Mann-Whitney U test was used for comparisons between patients with and without target body weight. Significance was set at P < 0.05.
Results
Patients’ Characteristics
A total of 45 patients were initially enrolled in the study. Seven patients were excluded from the study due to loss of follow-up (n = 3), intolerance of exercise (n =
2), worsening edema (n = 1), and poor control of hypertension (n = 1). Finally, 38 CKD patients completed the study, including 8 with overweight and 30 with obesity. The demographic and clinical characteristics of the overweight and obese patients are presented in Table 1. The mean age was 42.3 ± 11.3 years (range: 20 to 57 years), and mean BMI was 31.2 ± 6.0 Kg/M2 (range: 24.2 to 58.0 Kg/M2).
Effect of body weight control in obese CKD patients
At the end of the 8-week intervention, the weekly self-reported 24-hour caloric intake diaries were collected by the patients’ dietitians, who had tailored individual dietary recommendations so that patients could meet the estimated daily calorie requirements for body weight control. Decreases in BW and BMI were found in 34 patients (89.5%), and there were significant differences between baseline values and those assessed after the body weight intervention program. The mean weight reduction was -3.7 ± 3.0 kg (range: -10.2 kg to 4.8 kg), and the percentage of body weight reduction was -4.4 ± 3.5% (range: -12.1% to 4.9%). The overall reduction in total body fat was from 27.2 ± 7.5 kg at baseline to 25.2 ± 7.5 kg after the program (＜0.001). The reduction in body fat content was from 33.9 ± 4.9% at baseline to 32.1 ± 5.2% after the program ( ＜ 0.001). Moreover, total body muscle mass was also reduced from 49.2 ± 10.9 kg at baseline to 48.5 ± 11.3 kg after the program, even with a combination of diet control and regular exercise, and this reduction was global with lower muscle mass noted in upper limbs, lower limbs, and trunk.
Compared with baseline values, at the end of the body weight control intervention program there were significant improvements in systolic blood pressure (SBP) (135.2 ± 13.8 vs. 122.3 ± 8.3; P < 0.001), diastolic blood pressure (DBP)(81.0 ± 10.2 vs. 73.0 ± 8.4 ; P < 0.001), serum creatinine level (sCr) (1.1 ± 0.3 vs. 0.8 ± 0.3; P < 0.001), estimated glomerular filtration rate (eGFR) (75.9 ± 21.2 vs. 104.9 ± 38.1; P < 0.001), proteinuria (76.3% vs. 50.0%; P = 0.02), fasting blood sugar (FBS) (104.8
± 21.4 vs. 96.1 ± 20.5; P < 0.001), cholesterol (Chol) (189.5 ± 33.6 vs. 178.2 ± 24.3; P = 0.005), low-density lipoprotein cholesterol (LDL-C) (118.8 ± 33.1 vs. 97.7 ± 31.6; P = 0.001), and waist circumference (97.9 ± 14.9 vs. 91.8 ± 15.6; P < 0.001), but total body muscle mass was lower (49.2 ± 10.9 vs. 48.5 ± 11.3; P = 0.001) as shown in table 2.
Clinical changes in patients who reached target body weight control
Table 3 shows that in patients who reached the target body weight, i.e., a reduction in BW greater than 3% (80.6 ± 26.8 kg) compared with baseline value (85.9 ± 27.8 kg; P < 0.001), there was a greater reduction in total body fat content (-2.1%) than that in patients who did not reach the target body weight (-0.1%; P = 0.001). Patients with target BW had a decrease in total muscle mass of -1.2% compared with the baseline value, which was exactly higher than that in patients who did not reach the target BW (P = 0.026). The greatest reduction in muscle mass was found in the trunk (-0.5% vs. 0.0%; P = 0.012) and lower limbs (-0.5% vs. 0.0%; P = 0.033). The laboratory data disclosed significant reductions in Chol (-19.3% vs. 0.7%; P = 0.007), LDL-C ( -37.6% vs. 3.7%; P < 0.001), and UA (-0.8% vs. 0.0%; P = 0.025) in obese CKD patients with target body weight compared with those without.
Improvements in physical fitness after the body weight intervention program
After the 8-week physical exercise training and education program, the patients who reached the target body weight, i.e., a greater than 3% reduction compared with baseline, improved their cardiorespiratory endurance in the 800-meter running test (375.1 ± 64.7 sec vs. 327.1 ± 84.0 sec; P = 0.001, Figure 1A), in the abdominal muscle strength and endurance sit-up test (13.6 ± 9.1 number/min vs. 19.9 ± 9.2; P = 0.005, Figure 1B), and in the lower back flexibility sit and reach test (18.8 ± 10.9 cm vs. 27.8 ± 10.9 cm; P < 0.001, Figure 1C), comparing baseline and post-intervention data, respectively. Even for patients who did not reach the target body weight, their
flexibility was also significantly improved from the baseline (15.2 ± 9.3 cm) by the end of the 8-week training (24.5 ± 9.3 cm; P = 0.002, Figure 1C). In addition, abdominal muscle endurance (12.9 ± 7.6 cm vs. 17.3 ± 8.9 cm; P = 0.008, Figure 1B) was significantly improved after the 8-week training compared with the baseline. Analysis of the total calories and nutrient contents
Table 4 shows the analysis of the weekly self-reported 24-hour caloric intake diaries and found no differences in total calorie and nutrient contents at the baseline between groups. After the 8-week intervention, there were significant differences between obese CKD patients with and without target body weight in total calorie (1501.9 ± 200.9 kcal/day vs. 1809.5 ± 196.2 kcal/day; P < 0.001), and nutrient components which included protein (59.3 ± 11.3 gm/day vs. 71.0 ± 14.9 gm/day; P = 0.019), carbohydrate (201.6 ± 26.9 gm/day vs. 226.6 ± 34.8 gm/day; P = 0.030), and fat (50.9 ± 11.2 gm/day vs. 68.8 ± 12.7 gm/day; P < 0.001). This pattern of macronutrient consumption appears to confirm that at the end of the lifestyle intervention program, the tailored individual dietary recommendations were effective at enabling the patients to meet the estimated daily calorie requirements for body weight control. Our analysis of dietary composition also found that most obese CKD patients with target body weight ate a recommended dietary regimen with total fat not exceeding 30% of calories, but the percentage of fat consumed by most patients who did not achieve the target body weight was greater than 30%.
Discussion
Overweight, obesity, and CKD have become major public health issues in many countries over the past few decades. The relationship between overweight/obesity and CKD appears to be related to increasingly sedentary lifestyles with insufficient physical activity and excess compact caloric consumption [13-15]. There has also been a persistent rise in obesity-related metabolic effects, such as hypertension
[16-18], diabetes mellitus [19], dyslipidemia [19-21], and atherosclerosis [22-24], which participate in the progression of kidney disease. In patients with obesity, weight reduction can be an important adjunct to anti-hypertensive interventions, insulin sensitivity and lipid control [25], as well as improvement of proteinuria [26-29]. Such improvements should have beneficial effects in slowing the progression of CKD.
In the present study, weight reduction was shown to improve BP control, Chol, and LDL-C in overweight and obese CKD patients through a combination of diet control and exercise. The lipid nephrotoxicity hypothesis, proposed over three decades ago, suggests that proteinuria, decreased albumin levels, and the resultant hyperlipidemia may cause glomerulosclerosis in a manner similar to the hypothesized mechanism of atherosclerosis [4-7]. Circulating LDL has a charge affinity for glycoaminoglycans in the glomerular basement membrane and further increases its permeability. LDL selectively enhances the expansion of the mesangial matrix and modifies cell-matrix interactions in lipid-induced renal damage. Furthermore, precipitation of LDL is also known to cause tubulointerstitial disease [20,30-32].
Obesity also increases metabolic demands on the kidney. The number of nephrons does not increase as an individual gains weight, yet the glomerular filtration rate and renal plasma flow must increase in order to meet the higher metabolic demands. Weight reduction appears to cause a pronounced decrease in proteinuria in the absence of any other medical intervention [4-7]. A similar result was found in the present study, which showed marked improvements in renal profile, eGFR and renal function after weight reduction. Besides the hemodynamic changes seen after weight reduction, we also found patients’ total muscle mass, especially in the trunk and lower limbs, was reduced concomitantly with decreased total body fat after the body weight intervention program. sCr production essentially reflects lean body mass, so absolute sCr production declines with decreasing muscle mass [33]. In the short term, a
beneficial effect is observed with body weight reduction, but long-term observation is needed to determine whether this results in any deleterious effects.
However, our findings demonstrated clear evidence of improvements in cardiorespiratory endurance, abdominal muscle strength and endurance, as well as flexibility of the lower back after the 8-week physical exercise training and education program. The patients’ less sedentary lifestyles combined with sufficient physical activity improved their health status, and we expect they will regain their lost muscle mass with consistent exercise in the long-term.
There were several limitations in this analysis. First, the duration of the study was relatively short and only a small number of overweight and obese CKD patients were enrolled, so it was not possible to demonstrate a significant decrease in proteinuria despite improvements in dyslipidemia and renal function during the intervention period. Second, most patients were CKD stage 1 or stage 2 (81%) with mild hematuria and/or proteinuria, and thus these early-stage patients were prone to remission by weight reduction. Third, it is unclear whether the muscle mass reduction that accompanied caloric control had any deleterious effects. Fourth, errors in self-reported dietary intake may have confounded the results. It was not possible to precisely measure individual nutrition components and caloric intake during the study period. An additional study limitation is that the population studied may differ from others around the world, particularly those in Western countries, and thus any comparisons should be conducted with caution. Finally, the design of the study did not include a control group and therefore it was not possible to exclude several confounding factors, including regression toward the mean, improved compliance with medication, closer clinical control, and changes in season. Further research using different study designs are required to confirm the beneficial effects of a diet and exercise program in CKD obese patients that were observed in this investigation.
In conclusion, a combination of dietary management and exercise was associated with improvements in health-related physical fitness, blood pressure control, dyslipidemia and renal profiles in overweight and obese CKD patients. Supportive individualized programs for lifestyle change could therefore exert beneficial effects in overweight and obese CKD patients, but further long-term trials with additional CKD stages and a larger patient population are required to elucidate the optimal combination of dietary management and exercise.
Practical Application
Obesity may initiate and/or accelerate kidney damage. In this study, we demonstrated that supportive individualized programs for lifestyle change with dietary management and exercise were associated with improvements in health-related physical fitness, cardiovascular risk factors (BP and lipid control) and renal profiles in overweight or obese early CKD patients (stage 1-3). Reduction of body weight might be an important intervention in order to reduce the prevalence of renal impairment.
Acknowledgments
The authors thank Associate Professor Li-Yu Chen from Tunghai University for providing the “Health-related Physical Fitness” program which was used for the physical exercise training and education of patients in this study. The study was supported by Taichung Veterans General Hospital.
Disclosure
The authors declare no conflict of interest.
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