EVALUATION OF NUTRITIONAL STATUS OF PERITONEAL DIALYSIS PATIENTS BY BIOIMPE- DANCE ANALYSIS

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1 Acta Medica Mediterranea, 2016, 32: 685 EVALUATION OF NUTRITIONAL STATUS OF PERITONEAL DIALYSIS PATIENTS BY BIOIMPE- DANCE ANALYSIS HAKAN AKDAM 1, ALPER ALP 2, ÖZGÜL ÖZBEK 3, AYŞEGÜL KAHRAMAN 3, MELIH ÖZIŞIK 1, HAYRI ÜSTÜN ARDA 4, YAVUZ YENIÇERIOĞLU 1 1 Adnan Menderes University, Faculty of Medicine, Department of Internal Medicine, Division of Nephrology, Aydin, Turkey - 2 İzmir Tepecik Training and Research Hospital, Nephrology Clinic, İzmir, Turkey - 3 Adnan Menderes University Adnan Menderes University Practice and Research Hospital, Peritoneal Dialysis Unit, Aydin, Turkey - 4 Adnan Menderes University, Faculty of Medicine, Department of Internal Medicine, Aydin, Turkey ABSTRACT Introduction: Malnutrition is quite common in peritoneal dialysis patients and is associated with high mortality. Bioimpedance indices and phase angle are used frequently in nutritional studies. Phase angle measured by bioimpedance analysis indicates body cell mass and soft tissue mass and changes in the quality and quantity of the mass; therefore, it is used as a nutritional marker. We aimed to evaluate nutritional status of peritoneal dialysis patients by bioimpedance analysis. Materials and methods: 38 peritoneal dialysis patients and 37 healthy individuals were studied. All individuals bioimpedance indices, phase angle measurements (800 μa current, 50 khz frequency) were carried out by using multifrequency bioimpedance device. Nutritional biochemical markers were measured. Results: Peritoneal and control group phase angle were detected 4.48±0.86 and 5.97±0.85, respectively (p<0.001). Albumin, total protein, transferrin, potassium, calcium, hemoglobin, HDL-cholesterol levels were significantly lower in peritoneal group. The mean normalized protein catabolic rate (npcr) was found to be 1.41±0.44 g/kg/day, in peritoneal dialysis patients. There was a significant positive correlation between phase angle and npcr (p=0.001, r=0.516). Phase angle was positively correlated with albumin, total protein, transferrin, potassium, hemoglobin, body cell mass/weight, lean tissue mass/weight, lean tissue index, body cell mass/weight, and negatively correlated with age, creatinine, phosphorus, parathyroid hormone, alkaline phosphatase, C-reactive protein, fat tissue mass/weight, fat tissue index. Independent predictors of phase angle were albumin, age and lean tissue index revealed in regression analysis. Conclusion: Phase angle was significantly lower in peritoneal dialysis patients. Bioimpedance parameters, especially phase angle reflect the nutritional status in peritoneal dialysis patients. Key words: Bioimpedance, lean tissue index, nutrition, phase angle, peritoneal dialysis. DOI: / _2016_3_75 Received June 30, 2015; Accepted January 02, 2016 Introduction Malnutrition in peritoneal dialysis patients is quite common, affecting approximately 70% of patients (1). Inadequate intake of protein and energy with nutrients, increased catabolism, anorexia, metabolic abnormalities, loss of protein and amino acids from peritoneal membrane as well as insufficient dialysis are the main causes of malnutrition. Malnutrition adversely affects clinical outcomes of patients and is associated with high mortality. Early diagnosis and treatment of malnutrition in dialysis patients may improve survival and nutritional status (2,3). Decreased levels of nutritional markers such as serum albumin, prealbumin, creatinine and cholesterol levels are important risk factors for mortality in peritoneal dialysis patients (2,4,5). Nutritional state in dialysis patients can be assessed by anthropometric, biochemical parameters and body composition analysis by the bioimpedance method (2,6). Bioimpedance analysis in the assessment of body composition is a practical, non-inva-

2 686 Hakan Akdam, Alper Alp et Al sive method, enabling the evaluation of body fat mass, lean mass, and water compartments of the body. This analysis is based on the resistance of the body compartments to an alternating electrical current, and has a two vector component: resistance and reactance. Resistance based on the water high conductivity measures the tissue hydration status. Bone and fat can be easily distinguished since they contain low amounts of water (6-8). The capacitance of cell membranes, tissue interfaces, electrical charge of cells acting as condensers provides the reactance. Phase angle is an objective parameter to provide information about the patients nutritional risk that is measured by bioimpedance method, and it is considered as an indicator of cells well-being, reflecting better cell function (6,8). Phase angle indicates body cell mass and soft tissue mass and changes in the quality and quantity of the mass; therefore, it is used as a nutritional marker in the studies. A positive association has been shown between the phase angle and survival in lung cancer, AIDS, cirrhosis, severe patients and dialysis patients. The assessment of clinical course, monitoring of disease progression according to the other serum or anthropometric nutrition markers the phase angle analysis is considered to be a superior tool (6, 7, 9-12). In this study, we aimed to evaluate nutritional status of peritoneal dialysis patients by bioimpedance analysis and with phase angle, and to determine the relationship of these parameters with the biochemical parameters. Materials and methods A total of 38 patients undergoing peritoneal dialysis at least 3 months and 37 healthy individuals as control group were included in the study. Patients with active infection and who had peritonitis in the previous 3 months were excluded from the study.this study was approved by the Local Ethics Committee and was conducted in accordance with Declaration of Helsinki. All participants were informed and informed consent was obtained before the study. Duration of peritoneal dialysis, etiologies of end stage renal disease was recorded from the patient s medical chart. All participants general physical examination was carried out, age, gender was recorded and arterial blood pressure, height and weight were measured. The body mass index was calculated by the weight (kg)/height (m 2 ) formula. Biochemical analysis Peritoneal dialysis patients were evacuated the peritoneal fluid from the abdominal cavity at 23 o clock the night before the measurement day. Blood sample was obtained for biochemical parameters of all participants in the morning after fasting for 10 hour. Fasting blood samples of glucose, urea, creatinine, potassium, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-cholesterol), low-density lipoprotein cholesterol (LDL-cholesterol), uric acid, total protein, albumin, C-reactive protein (CRP), hemoglobin levels were measured. Protein catabolic rate (PCR) was calculated from the Randerson equation: PCR (g/day) = 5.02 x (Urea Generation Rate in mg/min ), and Normalized PCR (npcr) was obtained by dividing it by actual dry body weight (13,14). Urea Generation Rate (mg/min) was calculated as total urea nitrogen recovery in dialysate and urine per day/1440 min. Bioimpedance analysis The measurement of phase angle and body composition was carried out using portable multi frequency bioimpedance spectroscopy device (BCM ) (Fresenius Medical Care AG & Co., Bad Homburg, Germany). The measurement was performed on the day of the blood collection, an after spending 10 minutes supine, with 4 conventional electrodes placed 2- by-2 in the ipsilateral hand and foot. Peritoneal dialysis patients measurements performed with empty peritoneal cavity. The device (BCM ) measures the impedance spectroscopy at 50 different frequencies between 5 khz and 1000 khz. The total body water, intracellular water, extracellular water, lean tissue mass (LTM) and fat tissue mass (FTM) were calculated by the system software (15). These parameters were adjusted on a percentage basis to estimated body weight of each patient (7). The LTM and FTM were normalized to the body surface area to obtain lean tissue index (LTI=LTM/height 2 ) and fat tissue index (FTI=FTM/height 2 ) (6,15). Phase angle measurements were performed an 800 μa current at a frequency of 50 khz. Phase angle was calculated using the following equation: Phase Angle = (Reactance/Resistance) X 1800 /π (6,8,16). Statistical analysis The statistical analyses were performed using the Statistical Package for Social Sciences for

3 Evaluation of nutritional status of peritoneal dialysis patients by bioimpedance analysis 687 Windows version 17 (SPSS Inc., Chicago, IL, USA) software package. Quantitative variables were expressed as mean ± standard deviation and qualitative variables as number and percentages (n, %). The accordance of quantitative data with normal distribution was examined with the Kolmogorov-Smirnov test. Student s t-test was used to compare normally distributed variables. Chi-square test was used for comparison of qualitative variables. The relationship between the variables was evaluated using Pearson's correlation coefficient. Backward multiple linear regression analysis was performed to determine variables associated with phase angle. A P value <0.05 was considered significant. Results Mean age of the peritoneal dialysis patients was 51.7±15.9 years, and 31.5% of them were female. Duration of peritoneal dialysis was found to be 36.6±36.8 (range: months) months. The causes of end stage renal disease were hypertension (36.8%), diabetes (21.1%), post renal etiologies (13.2%), glomerulonephritis (10.5%), polycystic kidney disease (2.6%), and other/unknown (15.8%). Mean age, body mass index and gender distribution were similar in both groups. In the peritoneal dialysis group, serum albumin, total protein, transferrin, potassium, calcium, hemoglobin, HDL-cholesterol levels were significantly lower. As expected, peritoneal dialysis patients had significantly higher urea, creatinine, uric acid, phosphorus, alkaline phosphatase, parathyroid hormone, CRP levels than healthy controls (Table 1). In peritoneal dialysis group and the control group phase angle were detected to be 4.48±0.86 and 5.97±0.85, respectively, the difference was significant (p<0.001). Adjusted on a percentage basis to body weight of body cell mass/weight, lean tissue mass/weight, total body water/weight, intracellular water/weight, lean tissue index, total body water were significantly lower in peritoneal dialysis group. Fat tissue mass/weight, fat tissue index was significantly higher in peritoneal dialysis group (Table 2). The mean PCR and npcr were found 98.4±29.6 g/day, 1.41±0.44 g/kg/day, respectively in peritoneal dialysis patients. Phase angle was showed a strong positive correlation with PCR (p=0.010, r=0.414) and npcr (p=0.001, r=0.516), no correlation was found between phase angle and duration of peritoneal dialysis (p=0.375, r=-0.148) (Figure 1). Parameters Peritoneal Dialysis Patients Healthy Control / (n) 12/26 15/ Age (year) 51.7± ± Body mass index 27.1± ± Creatinine 8.5± ±0.1 <0.001 Urea 104.2± ±9.5 <0.001 Total protein (g/dl) 6.7± ±0.4 <0.001 Albumin (g/dl) 3.4± ±0.2 <0.001 Glucose 106.9± ± Uric acid 6.1± ±1.1 <0.001 Ferritin 472.9± ± Transferrin (mg/dl) 163.5± ±45.6 <0.001 Potassium (mmol/l) 4.0± ±0.2 <0.001 Calcium 8.8± ±0.3 <0.001 Phosphorus 4.4± ±0.4 <0.001 Parathyroid hormone (pg/ml) Alkaline phosphatase (U/L) C-reactive protein Total Cholesterol Triglycerides HDL-Cholesterol LDL-Cholesterol 486.7± ±20.0 < ± ±24.5 < ± ± ± ± ± ± ± ±13.7 < ± ± Hemoglobin (g/dl) 11.0± ±1.6 <0.001 Table 1: Demographic features of groups. Bivariate correlation analysis that included all participants was made and phase angle was found to be positively correlated with albumin, total protein, transferrin, potassium, hemoglobin, body cell mass/weight, lean tissue mass/weight, total body water/weight, intracellular water/weight, lean tissue index, body cell mass/weight, and was negatively correlated with age, creatinine, phosphorus, parathyroid hormone, alkaline phos- P

4 688 Hakan Akdam, Alper Alp et Al phatase, CRP, fat tissue mass/weight, fat tissue index (Table 3, Figure 2). Multiple regression analysis showed that albumin (beta=0.305, p<0.001), age (beta= , p=0.001) and lean tissue index (beta 0.678, p<0.001) were independent predictor of phase angle, and these factors were accounted for 91.7% of phase angle result. Parameters Discussion Peritoneal Dialysis Patients Healthy Control Phase angle 4.48± ±0.85 <0.001 Fat tissue mass/weight Lean tissue mass/weight Body cell mass/weight Total body water/weight Extracellular water/weight Intracellular water/weight Lean tissue index 55.3± ± ± ± ± ±9.6 < ± ± ± ± ± ± ± ±3.0 <0.001 Fat tissue index 15.7± ± Table 2: Bioimpedance features of groups. Bioimpedance analysis is widely used in the assessment of nutritional status in various chronic diseases. In previous studies body composition parameters and phase angle was detected lower in chronic diseases and severely malnourished patients (6-9,12). The mean phase angle value was detected approximately 6.0 in peritoneal dialysis patients (4,6). In another study, the phase angle measurement was 4.7 in continuous ambulatory peritoneal dialysis patients (17). Our study revealed phase angle value 4.48 in peritoneal dialysis patients. In previous studies, phase angle was evaluated by different brands and models of bioimpedance device and even in normal healthy population reference values are not fully defined, also it is reported to vary by race (2,4, 6,9,17). Our lower phase angle results were thought to be affected by the reasons mentioned above. Phase angle is a composition of the resistance and reactance abilities of the human body fluid and cellular membranes. Phase angle increases with high reactance and reduced by high resistance. P Parameters Correlation Coefficient Age (year) <0.001 Body mass index Therefore, high phase angle while pointing to intact cell membranes in large quantities, low phase angle indicates cell death or reduced cell integrity (6,8,16). In healthy adults, age, gender and body mass index was found to be major determinants of phase angle. Increase in fat mass and declining proportion P Creatinine <0.001 Total protein (g/dl) <0.001 Albumin (g/dl) <0.001 Uric acid Ferritin Transferrin (mg/dl) <0.001 Potassium (mmol/l) Calcium Phosphorus Parathyroid hormone (pg/ml) Alkaline phosphatase (U/L) C-reactive protein Total Cholesterol < Triglycerides HDL-Cholesterol LDL-Cholesterol Hemoglobin (g/dl) <0.001 Fat tissue mass/weight Lean tissue mass/weight Body cell mass/weight Total body water/weight Extracellular water/weight Intracellular water/weight Lean tissue index < < < < < <0.001 Fat tissue index (kg/m 2 ) <0.001 Table 3: Bivariate correlation between the phase angle measured at 50kHz and biochemical, anthropometric and bioimpedance parameters.

5 Evaluation of nutritional status of peritoneal dialysis patients by bioimpedance analysis 689 of body water with aging causes resistance to increase, likewise muscle mass loss causes reactance to decrease in turn resulting in reduction in phase angle (8). We found that age was major determinant of phase angle however, study could not determine relationship with gender and body mass index. Figure 1: Correlation between phase angle and normalized protein catabolic rate in peritoneal dialysis patients. (Abbrevation. npcr: normalized protein catabolic rate) Figure 2: Correlation of phase angle with albumin, lean tissue index, age, and c-reactive protein. Albumin loss in peritoneal dialysis is about 4 gram per a day (18). These losses are usually compensated by an increased albumin synthesis. However, this process is suppressed in the presence of inflammation. Low albumin level has been considered as a marker of co-morbidity, inflammation and malnutrition (3,19). Several reports used albumin together with phase angle analysis to evaluate the nutrition. Fein et al. (19) reported phase angle was directly correlated with albumin, total protein, and creatinine. They concluded that serum albumin was the only best predictor of phase angle in peritoneal dialysis. Other studies also reported that phase angle was positively correlated with serum albumin, creatinine and total cholesterol (7,20). Phase angle was shown to be significant determinant of albumin (20). The npcr represents daily dietary protein intake in dialysis patients, and it has been recognized as nutritional marker. The npcr correlated directly with phase angle and lower npcr association with poor nutrition, and increase in all-cause mortality in peritoneal dialysis patients has been reported (21). In the present study, we documented positive correlation between phase angle and albumin, creatinine and npcr. We also confirmed that albumin was the major indicator of phase angle; these results are in accordance with the previous studies (7,19-21). Glucose containing dialysate contributes to increased fat mass in peritoneal dialysis due to carbohydrate load (19). An increase in fat mass in peritoneal dialysis patients was shown in several studies (2,7,17,22). Decrease in weight adjusted lean tissue mass, intracellular water, body cell mass and increase in fat mass were also reported in peritoneal dialysis patients (7). Low phase angle may be specifically due to increased fat mass and decreased muscle mass in peritoneal dialysis patients (7,17,22). This data is in accordance with our results. Our study has shown that serum albumin, transferrin, potassium, hemoglobin, body cell mass/weight, lean tissue mass/weight, lean tissue index, body cell mass/weight were decreased and CRP, fat tissue mass/weight, fat tissue index were increased in peritoneal dialysis patients. These results confirm the relationship between serum nutritional markers and bioimpedance parameters as others reported previously (4 7,17,22,23). There is a close relationship between mortality and phase angle. A study reported that a phase angle <6 has a relative risk of mortality per year of 4.1 compared to those who have a higher phase angle (24). Phase angle is an independent predictor of more than one, two, five years survival in peritoneal dialysis patients (2,4,7,8,17,23,24). Limitations of our study was cross-sectional case-control study, therefore we could not performed survival analysis. Uremic malnutrition, chronic inflammation, peritoneal albumin loss, carbohydrate load, fat mass gain, less dietary protein intake, muscle mass depletion are highly prevalent in peritoneal dialysis patients (2,3,8,18,19,22). A low phase angle is probably due to consequence of the aforementioned processes.

6 690 Hakan Akdam, Alper Alp et Al In conclusion, bioimpedance analysis is a simple, reproducible, clinically useful method to assess nutritional status. Bioimpedance parameters, especially phase angle reflect the nutritional status in peritoneal dialysis patients, and may be useful in monitoring nutritional status in routine clinical care. References 1) Prasad N, Gupta A, Sinha A, Sharma RK, Kumar A, et al. Changes in nutritional status on follow-up of an incident cohort of continuous ambulatory peritoneal dialysis patients. J Ren Nutr 2008; 18: ) Avram MM, Fein PA, Rafiq MA, Schloth T, Chattopadhyay J, et al. Malnutrition and inflammation as predictors of mortality in peritoneal dialysis patients. Kidney Int 2006; 70: ) Wang T, Heimbürger O, Bergström J, Lindholm B. Nutritional problems in peritoneal dialysis: an overview. Perit Dial Int 1999; 19: ) Mushnick R, Fein PA, Mittman N, Goel N, Chattopadhyay J, et al. 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Can Bioimpedance Measurements of Lean and Fat Tissue Mass Replace Subjective Global Assessments in Peritoneal Dialysis Patients? J Ren Nutr 2015; 25: ) Segall L, Mardare NG, Ungureanu S, Busuioc M, Nistor I, et al. Nutritional status evaluation and survival in haemodialysis patients in one centre from Romania. Nephrol Dial Transplant 2009; 24: Corresponding author HAKAN AKDAM Adnan Menderes University, Faculty of Medicine, Department of Internal Medicine, Division of Nephrology 09100, Aydin (Turkey)