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Use of bioelectrical impedance techniques for monitoring nutritional status in patients on maintenance dialysis
REVIEW
Use of Bioelectrical Impedance Techniques for Monitoring Nutritional Status in Patients on Maintenance Dialysis Francis Dumler, MD,* and Cristina Kilates, RD, MS† Malnutrition continues to be an important correlate of survival in dialysis patients. Nutritional surveillance at the clinical level requires use of simple, reasonably accurate, and easily accessible techniques for multicompartmental body composition analysis. Unfortunately, although gold standard methodologies (body density by underwater weight, total body water by isotope dilution, bone mineral content by neutron activation, total body potassium by 40K whole body gamma counting) provide very precise assessments, they are not applicable to routine clinical practice. Because of its availability and simplicity, bioelectrical impedance (BEI) has significant potential as a complement to standard anthropometric techniques in the nutritional monitoring of patients with chronic renal failure. Consistency of technique and standardization of BEI equipment are essential for reproducibility of results. Several studies have validated the use of total body water by BEI as a surrogate for isotope dilution methods in dialysis patients, whereas others have established an excellent correlation with the volume of distribution of urea as measured by urea kinetic volume. Bioimpedance analysis for measurement of lean body mass has been extensively evaluated in stable healthy populations, with results similar to those obtained using hydrodensitometry and total body potassium. In dialysis patients, accuracy is contingent on a stable hydration status and/or appropriate correction for changes in extracellular volume status over time. Recent publication of bioimpedance norms for the hemodialysis population allows better comparisons with the national reference population studied as part of the National Health and Nutrition Examination Survey III (US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics, Hyattsville, MD). BEI methodology is a practical bedside tool for assessment of body composition that provides more consistent and reproducible results than standard anthropometry alone. r 2000 by the National Kidney Foundation, Inc.
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*Chief, Division of Nephrology, William Beaumont Hospital, Royal Oak, MI, and Clinical Professor of Internal Medicine, Wayne State University, Detroit, MI. †Renal Research Dietitian, Division of Nephrology, Henry Ford Hospital, Detroit, MI. Address reprint requests to Francis Dumler, MD, Division of Nephrology, William Beaumont Hospital, 3535 W 13 Mile Rd, Suite #642, Royal Oak, MI 48073-6705. r 2000 by the National Kidney Foundation, Inc. 1051-2276/00/1003-0002$3.00/0 doi:10.1053/jren.2000.7916
also assumed that maintenance dialysis therapy would be too risky for diabetics patients and the elderly, thereby resulting in premature death. Of note in this regard, the most recent data from the United States Renal Data System shows the highest increase in ESRD (1988 to 1997) among the elderly (80⫹ years: 277%; 70-79 years: 160%). As a comparison, the corresponding figure for those younger than age 60 is 73%. In addition, diabetes accounted for the greatest increment (180%) in ESRD, followed by hypertension (86%) and glomerulonephritis (37%). These demographic changes place the current ESRD patient population at a very high risk for malnutrition because of associated multiple comorbid illnesses.1 In spite of continuous advances in dialytic
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Journal of Renal Nutrition, Vol 10, No 3 ( July), 2000: pp 116-124
HE END-STAGE renal disease (ESRD) program was initially envisioned as part of a disease management strategy that would sustain life and improve health, allowing patients to eventually return to work and continue contributing to society. That initiative
BIOIMPEDANCE ANALYSIS IN DIALYSIS PATIENTS
therapy and improvements in the management of cardiovascular disease and infections, mortality in the dialysis population continues to be unusually high. Inadequate nutrition has been clearly identified as a significant risk factor for survival, and affecting 30% to 70% of patients.2-5 Unfortunately, very few registries have recorded nutritional status on a regular basis. Hypoalbuminemia is another substantial marker for increased morbidity and mortality in dialysis patients. In the elderly, hypoalbuminemia is a risk factor even in individuals with normal renal function.6 Early recognition of malnutrition, implementation of nutritional interventional strategies, and longitudinal monitoring of body composition are intuitively necessary for the appropriate management of dialysis patients. Unfortunately, current methods for nutritional analysis, when applied to the clinical setting, are time-consuming, impractical, nonspecific, or affected by the metabolic disturbances associated with uremia. Classic body composition analysis defines constituents as fat or fat-free. The former is a fairly homogenous compartment, whereas the latter includes water, protein, bone, and small amounts of various components such a glycogen. Several methods are available for independent assessment of these individual components. Estimates using these multiple compartmental models are independent of assumed numerical relationships between components.7,8 Unfortunately, although body density by underwater weight and residual lung volume, total body water by isotope dilution, bone mineral content by neutron activation, and total body potassium by gamma counting measurements will provide a very accurate multicompartmental analysis of body composition, they are not applicable to routine clinical patient care. From a utilitarian perspective, body composition analysis methods can be categorized as reference (whole body density, isotope dilution, total body potassium, in-vivo neutron activation), bedside (anthropometry, bioelectrical impedance [BEI], near infra-red interactance), and intermediate (dual energy x-ray absorptiometry [DEXA]). Because of their simplicity and availability, anthropometry and bioelectrical impedance have received significant attention from the renal community.
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BEI Analysis Charged ions within a cell and its surrounding fluid are unevenly distributed across the membrane wall. The potential difference of about 100 mV is a result of the lag of Cl⫺ ions during K⫹ extrusion. Cell membranes consist of a layer of nonconductive lipophilic material interposed between 2 layers of conductive protein molecules. This structure makes cells behave as capacitors (objects capable of storing electrical charge) when exposed to an electric current, with the cell membrane acting as the dielectric insulating material.9-12 Mammalian tissues conduct an electrical current in proportion to their water and electrolyte content. Body fluids and electrolytes, mostly contained in lean tissues, have highly conductive, low resistance electrical pathways. Skin, fat, and bone are poor conductors and offer a high resistance. This tissue-specific resistance is measured by the voltage drop between 2 points. Reactance is the opposition to the flow of electric current caused by the electrical charge stored in the cell membrane. Only cell membranes offer reactance to electrical current.9-12 In the human body, the resistance and reactance components are aligned in both parallel and series orientations, with the vectorial components of impedance directly measured as resistance and reactance. Extracellular and intracellular fluid content defines the former, and the cell membrane the latter. In fat-free mass, these fluid compartments are in reality parallel fluid moieties separated by cell membranes; therefore, their impedance vector is more accurately determined with parallel models. Although arms and legs only account for 35% of total body volume, they represent approximately 85% of total body resistance.9-12 Very low frequency currents pass only through the extracellular fluid, whereas high frequency currents traverse both intracellular and extracellular paths. During single frequency BEI analysis, a small current (typically 800 µA, usually at a frequency of 50 kHz) is passed through the body over a 2-minute period. The instrument measures the resulting voltage produced between 2 electrodes. The impedance (Z) is mathematically calculated from the resistance (R) and reactance (Xc) vectors (Z2 ⫽ R2 ⫹ Xc2). The phase angle
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(arctangence of the ratio of reactance to resistance) is an index of cell membrane integrity and is particularly influenced by cellular metabolic function.13 In multifrequency BEI, the relationship between resistance and reactance is analyzed over a wide spectrum of frequencies (at least 100). At very low frequencies, the reactance is zero and measured impedance is all resistance. As the frequency rises, reactance increases, causing the phase angle to open until a maximum is reached in which all impedance is reactance. The mathematics describing these events is known as the Cole-Cole function and allows estimation of intracellular and extracellular body water.14,15 These complex profiles are influenced by cell size, membrane permeability, intracellular composition, and distribution of body fluids (which affects the amount of current shunting through interstitial spaces). Single frequency bioimpedance analysis has been used to calculate total body water, fat-free mass, and, more recently, body cell mass. This latter parameter is inclusive of total protein and intracellular water, and is considered the most metabolically active body compartment.13,16 Body cell mass quantitation by BEI closely correlates with those using measured exchangeable sodium and derived exchangeable potassium.17
Impact of Dialysis on BEI Measurements of Resistance and Reactance Several hemodialysis-related factors impact resistance and reactance measurements. Patientspecific variables include location of the hemodialysis access and body position at the time of assessment. Hemodialysis-related parameters relate to solute removal and degree of ultrafiltration. Studies conducted using continuous BEI monitoring during the entire hemodialysis procedure show a gradual and consistent increase in resistance, which reaches a plateau value at 150 minutes into dialysis. This change is present during dialysis regardless of fluid removal.18,19 Actually, the greatest increases are observed with pure ultrafiltration, whereas the least change is noted when hemodialysis is performed alone without ultrafiltration. Intermediate increases are noted during hemodialysis with fluid removal, as
is usual in the clinical setting.18 These changes are multifactorial and related to increases in specific resistance of body fluids, a rising hematocrit, changes in solute concentration, a varying distribution of intracellular and extracellular water and electrolytes, and loss of total body water.20 In our experience, resistance readings using the extremity with a functioning arteriovenous access for hemodialysis are consistently 10% lower than when using the controlateral limb. In addition, the dominant side also has higher resistance values. Others have found similar results.21,22 Differences in types of vascular access and use of dominant versus nondominant limbs can influence results and increase variability. We have found no clinical differences in resistance measurements in dialysis patients taken in the lying and sitting position. In healthy subjects, resistance measurements taken in the supine position are on average 2% higher than in the seated position.23 Finally, the presence of a central hemodialysis catheter may result in resistance readings 9% lower than in the controlateral side.22 No changes in resistance are observed in peritoneal dialysis patients after infusion or drainage of dialysate.24-26 This is related to slow solute and fluid mass transfer, and to the low contribution of the abdominal cavity (⬍10%) to total body resistance. Actually, BEI analysis does not detect fluid in the abdominal cavity, whether it is ascitis or dialysate.24-26 When using BEI analysis in the clinical setting, it is very important to pay attention to detail to minimize intra- and inter-patient variability. During longitudinal observation, absolute values are not as critical as detecting changes. But, the greater methodological variability, the lesser the sensitivity of the measurement. In our programs, we adhere to a strict protocol aimed at minimizing technical variability. All patients are evaluated 15 minutes after completion of hemodialysis, using the nonaccess side, in a sitting position with the back at 30° from the vertical, and with the footrest elevated. Limbs are placed at a 30° abduction. Continuous ambulatory peritoneal dialysis patients are measured in a similar manner during a regular clinic visit. Every effort is made to perform the study when patients are clinically at dry weight. All measurements and data analysis are performed under the direct supervision of our renal dietitians.
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Assessment of Body Composition Analysis by BEI Nutritional status optimization is essential to the care of dialysis patients. The need for prospective evaluation of body composition is a key element in achieving this goal. Assessment of total body water, lean body mass, fat mass, and body cell mass over time is of clinical importance to facilitate definition of dry weight adequacy and to identify individuals at particular risk for malnutrition. Several authors have validated the use of total body water by BEI as a surrogate for isotope dilution methods in dialysis patients,13,27 whereas others have established an excellent correlation with the volume of distribution of urea as measured by urea kinetic volume.28,29 It is important to note that although total body water estimates by BEI have the smallest bias and the best correlation with isotope quantitation, individual variations may be high enough to warrant more specific approaches. Some have suggested the use of segmental bioimpedance analysis for more accurate evaluation of rapid fluid changes, as this technique is more sensitive to fluctuations in the central (trunk) volume than whole body bioimpedance.30,31 Another recent approach is to define the state of hydration by using the bioimpedance vector analysis technique.32-34 Rather than calculating total body water from the bioimpedance measurements, this method plots resistance and reactance values factored by height, and defines the value and angle of the bioimpedance vector. An important benefit of using this direct measurement is the elimination of bias related to the use of population-derived constants and functions in the calculations. Another major advantage of vector analysis is the ability to identify the hydration status of an individual patient within 75% to 95% confidence ellipses predefined in a reference normal population. Single frequency BEI estimates intracellular and extracellular volumes by using derivative equations based on the phase angle relationship between reactance and resistance,10,13,35 whereas multifrequency BEI spectroscopy provides a more direct assessment of intracellular and extracellular volume.36 In general, overhydration in dialysis patients is mostly caused by increases in extracellu-
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lar rather than intracellular volume.27,37-39 In addition, most studies suggest that ultrafiltration during hemodialysis is primarily at the expense of the extracellular compartment. During hypotension, fluid is predominantly removed from the central compartment (trunk and central blood volume), with limb fluid volume remaining fairly stable.40 Assessment of lean body mass by BEI analysis has been extensively validated in stable healthy populations, with results similar to those obtained with hydrodensitometry and total body potassium.9,11,41-43 Transformation of resistance and reactance values from a series to a parallel model increases the accuracy of lean body mass estimates, as muscle mass is in reality composed of cells surrounded by interstitial fluid.10,12,42 Several studies in dialysis patients have compared lean body mass measurements by BEI with those obtained using dual energy x-ray absorptiometry. Although the number of patients studied is relatively small, there is a high degree of correlation and concordance between these 2 methods.13,41,44-46 Most important, both BEI and DEXA are influenced by the degree of tissue hydration.47,48 In edematous patients, excess water, exclusive to the extracellular compartment, alters the balance between intracellular and extracellular volumes. BEI equations using weight as a variable will apportion some of this excess fluid to the intracellular compartment, thereby falsely increasing lean body mass. The Deurenberg equation, which does not include the term weight, may provide some advantage in patients believed to be volume overloaded.49 Most studies of body composition in dialysis patients have been cross-sectional.13,16,18,24,26 This approach has been used to define quartiles for the hemodialysis population.50 Although no such reference data is available for peritoneal dialysis patients, we have found no differences in body composition between hemodialysis and peritoneal dialysis.51,52 Therefore, it is reasonable at present to use hemodialysis standards for all dialysis patients. Of greater significance, the recently completed National Health and Nutrition Examination Survey III (data available in CDROM format from US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics,
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Hyattsville, MD 20782-2003) survey has used BEI analysis to define general population norms. This provides a unique opportunity for evaluating the bioimpedance data in dialysis patients in relation to normative data from the general population that is specific for age, race, and gender. Most important is the potential for longitudinal follow-up of patients at risk for malnutrition. Several studies have reported on the use of BEI on interventional studies of malnutrition in nonrenal disease. In a refeeding study of malnourished patients, BEI predicted changes in body composition with greater prediction than anthropometry.53 In hyperthyroid patients, BEI has been used to evaluate lean body mass content before and after treatment.54,55 Bioimpedance techniques have also been used in the monitoring of hypopituitary patients treated with recombinant growth hormone.56,57 In chronic renal failure patients, decreases in body weight may not correlate with changes in lean body mass as measured by BEI, particularly when physical inactivity, fluid retention, and fat tissue increases are concurrent to muscle mass loss. In a previous study, 28% of hemodialysis patients lost body weight, whereas a decrease in lean body mass was identified in 41% of patients. In addition, only 3% of patients showed no change in lean body mass, whereas body weight remained neutral in 28% during a 12-month observation period.18 In peritoneal dialysis patients, serial BEI assessments identified a decrease in body weight in 36% of patients, whereas a loss of lean body mass was noted in 49%. Actually, among the 64% of patients with increasing body weights, BEI showed an actual loss of lean body mass in 24%.24 Others have reported similar increases in body weight caused by fat mass accumulation.58 A very recent study has evaluated lean body mass changes over a 6-month period in hemodialysis patients treated thrice weekly with recombinant growth hormone. Although there were no changes in body mass index, lean body mass by BEI increased by a mean of 3.9 kg, whereas in the placebo group it suffered a 1.2-kg decrease.59 Longitudinal body composition analysis using current BEI or DEXA techniques has the risk of interpreting an increase in total body water (overhydration) as lean body mass.60 Population-
specific equations currently developed for ESRD patients will yield superior predictive power, thereby minimizing longitudinal variability.61 Technologically advanced systems allowing separate evaluation of intracellular fluid and body cell mass will greatly facilitate assessment of body composition analysis in patients with abnormal water distribution.62,63 Body cell mass represents the active metabolic component of the body and encompasses all intracellular tissues and extracellular protein. The gold standard techniques for body cell mass measurements are neutron activation and total body potassium. It is clinically estimated by DEXA and BEI, with the latter systematically underestimating values by 19% relative to the former.13 Because of difficulties with tissue hydration and mathematical derivations to define body compartments, some authors have evaluated the relationship between direct impedance measurements and patient outcomes. The phase angle, a direct measure of cellular health and stability that reflects the extracellular to intracellular water ratio, can be conceptualized as a BEI summation value. Of interest, a variety of studies have shown the phase angle to be a significant predictor for survival in patients with acquired immunodeficiency syndrome and in patients with ESRD.64-66 These observations strongly suggest that use of phase angle, a powerful predictor of mortality, may become critical in the identification of individuals at particular risk who may benefit from intense scrutiny leading to optimization of therapies. In summary, BEI assessments of body composition in dialysis patients require attention to detail to minimize technique variability. The clinical experience with single frequency impedance analysis is greater than with multifrequency techniques. Factors to consider include hydration status, body position, hemodialysis access, and timing of measurements in relation to the dialysis procedure. Consistency of technique and standardization of BEI equipment are essential for reproducibility of results. Equations used in calculations must be age-, sex-, race-, body habitus–, and populationspecific whenever possible. Impedance vector analysis and phase angle are promising new applications that merit significant consideration in clinical practice.
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Appendix 1. Compilation of References Listed in This Review That Report on Bioelectrical Impedance Analysis Specific to the End-Stage Renal Disease Population 1. Talluri T, Maggia G: Bioimpedance analysis (BIA) in hemodialysis: Technical aspects. Int J Artif Organs 18:687-692, 1995 2. Chertow GM, Lowrie EG, Wilmore DW, et al: Nutritional assessment with bioelectrical impedance analysis in maintenance hemodialysis patients. J Am Soc Nephrol 6:75-81, 1995 3. Jabara AE, Mehta RL: Determination of fluid shifts during chronic hemodialysis using bioimpedance spectroscopy and an in-line hematocrit monitor. ASAIO J 41:M682-M687, 1995 4. Biasioli S, Foroni R, Petrosino L, et al: Effect of aging on the body composition of dialyzed subjects. Comparison with normal subjects. ASAIO J 39:M596-M601, 1993 5. Dumler F, Schmidt R, Kilates C, et al: Use of bioelectrical impedance for the nutritional assessment of chronic hemodialysis patients. Miner Electrolyte Metab 18:284-287, 1992 6. Sinning WE, DeOreo PB, Morgan AL, et al: Monitoring hemodialysis changes with bioimpedance. ASAIO J 39:M584M589, 1993 7. Kushner RF, deVries PMJM, Gudivaka R: Use of bioelectrical impedance analysis measurements in the clinical management of patients undergoing dialysis. Am J Clin Nutr 64:503S-509S, 1996 (suppl) 8. Woodrow G, Oldroyd B, Smith MA, et al: The effect of arteriovenous fistulae in haemodialysis patients on whole body and segmental bioelectrical impedance. Nephrol Dial Transplant 12:524-527, 1997 9. Di Iorio BR, Terracciano V, Bellizzi V: Bioelectrical impedance measurement: Errors and artifacts. J Ren Nutr 9:192197, 1999 10. Schmidt R, Dumler F, Cruz C, et al: Improved nutritional follow-up of peritoneal dialysis patients with bioelectrical impedance. Adv Perit Dial 8:157-159, 1992 11. Rallison LR, Kushner RF, Penn D, et al: Errors in estimating peritoneal fluid by bioelectrical impedance analysis and total body electrical conductivity. J Am Coll Nutr 12:66-72, 1993 12. Arkouche W, Fouque D, Pachiaudi C, et al: Total body water and body composition in chronic peritoneal dialysis patients. J Am Soc Nephrol 8:1906-1914, 1997 13. Ho LT, Kushner RF, Schoeller DA, et al: Bioimpedance analysis of total body water in hemodialysis patients. Kidney Int 46:1438-1442, 1994 14. Pastan S, Gassensmith C: Total body water measured by bioelectrical impedance in patients after hemodialysis. Comparison with urea kinetics. ASAIO J 38:M186-M189, 1992 15. Schmidt R, Dumler F, Cruz C: Indirect measures of total body water may confound precise assessment of peritoneal dialysis adequacy. Perit Dial Int 13:S224-S226, 1992 16. Zhu F, Schneidtz D, Wang E, et al: Validation of changes in extracellular volume measured during hemodialysis using a segmental bioimpedance technique. ASAIO J 44:M541-M545, 1998 17. Zhu F, Schneidtz D, Levin NW: Sum of segmental bioimpedance analysis during ultrafiltration and hemodialysis reduces sensitivity to changes in body position. Kidney Int 56:692-699, 1999 18. Piccoli A, for the Italian Hemodialysis-Bioelectrical Impedance Analysis (HD-BIA) Study Group: Identification of operational clues to dry weight prescription in hemodialysis using bioimpedance vector analysis. Kidney Int 53:10361043, 1998 19. Kouw PM, Olthof CG, ter Wee PMK, et al: Assessment of post-dialysis dry weight: An application of the conductivity measurement method. Kidney Int 41:440-444, 1992 20. Fisch BJ, Spiegel DM: Assessment of excess fluid distribution in chronic hemodialysis patients using bioimpedance spectroscopy. Kidney Int 49:1105-1109, 1996 21. Oe B, De Fijter WM, De Fijter CW, et al: Detection of hydration status by total body bioelectrical impedance analysis (BIA) in patients on hemodialysis. Int J Artif Organs 20:371-374, 1997 22. Zaluska WT, Schneidtz D, Kaufman AM, et al: Relative underestimation of fluid removal during hemodialysis hypotension measured by whole body bioimpedance. ASAIO J 44:823-827, 1998 23. Kotler DP, Burastero S, Wang J, et al: Prediction of body cell mass, fat-free mass, and total body water with bioelectrical impedance analysis: Effects of race, sex and disease. Am J Clin Nutr 64:489S-497S, 1996 (suppl) 24. Lo WK, Prowant BF, Moore HL, et al: Comparison of different measurements of lean body mass in normal individuals and in chronic peritoneal dialysis patients. Am J Kidney Dis 23:74-85, 1994 25. Woodrow G, Oldroyd B, Turney JH, et al: Measurement of total body water and urea kinetic modeling in peritoneal dialysis. Clin Nephrol 47:52-57, 1997 26. De Fijter WM, De Fijter CW, Oe PL, et al: Assessment of total body water and lean body mass from anthropometry, Watson formula, creatinine kinetics, and body electrical impedance compared with antipyrine kinetics in peritoneal dialysis patients. Nephrol Dial Transplant 12:151-156, 1997 27. Chertow GM, Lazarus JM, Lew NL, et al: Bioimpedance norms for the hemodialysis population. Kidney Int 52:16171621, 1997 28. Dumler F, Kilates C, Wagner C, et al: Surveillance of nutritional status in chronic dialysis patients. J Ren Nutr 7:194198, 1997 29. Dumler F, Falla P, Butler R, et al: Impact of dialysis modality and acidosis on nutritional status. ASAIO J 45:413-417, 1999
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Appendix 1. Compilation of References Listed in This Review That Report on Bioelectrical Impedance Analysis Specific to the End-Stage Renal Disease Population (Cont’d) 30. Briganti M, Emiliani G, Montanari A, et al: Longitudinal assessment of body composition in CAPD patients using bioelectric impedance analysis. A comparison with hemodialysis patients. ASAIO J 41:M725-M727, 1995 31. Johannsson G, Bengtsson B-A, Ahlme´n J: Double-blind, placebo-controlled study of growth hormone treatment in elderly patients undergoing chronic hemodialysis: Anabolic effect and functional improvement. Am J Kidney Dis 33:709-717, 1999 32. Bergia R, Bellini ME, Valenti M, et al: Longitudinal assessment of body composition in continuous ambulatory peritoneal dialysis patients using bioelectric impedance and anthropometric measurements. Perit Dial Int 13:S512-S514, 1993 (suppl 2) 33. Chertow GM, Laqarux JM, Lew NL, et al: Development of a population-specific regression equation to estimate total body water in hemodialysis patients. Kidney Int 51:1578-1582, 1997 34. Fisch BJ, Spiegel DM: Assessment of excess fluid distribution in chronic hemodialysis patients using bioimpedance spectroscopy. Kidney Int 49:1105-1109, 1996 35. Maggiore Q, Nigrelli S, Ciccarelli C, et al: Nutritional and prognostic correlates of bioimpedance indexes in hemodialysis patients. Kidney Int 50:2103-2108, 1996 36. Chertow GM, Jacobs DO, Lazarus JM, et al: Phase angle predicts survival in hemodialysis patients. J Ren Nutr 7:204-207, 1997
Appendix 2. Advantages and Disadvantages of Bioelectrical Impedance Analysis in the Clinical Evaluation of Chronic Renal Failure Patients Advantages
Disadvantages
ⴱ Small coefficient of variation for direct measurements ⴱ Easy technique to use and very practical in a clinic setting ⴱ Accurate and reproducible estimate of total body water ⴱ Better predictor of changes in body composition than anthropometry ⴱ Established bioelectrical impedance norms in the general population and hemodialysis patients
ⴱ Equipment calibration and method standardization are prerequisites ⴱ Lean body mass and fat mass measurements are influenced by the state of overhydration ⴱ Standard single frequency techniques do not detect fluid changes in the thoracoabdominal cavity ⴱ Technique not validated in amputees
References 1. U.S. Renal Data System, USRDS 1998 Annual Report. Bethesda, MD, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, April 1998 2. Lowrie EG, Lew NL: Death risk in hemodialysis patients: The predictive value of commonly measured variables and an evaluation of death rate differences between facilities. Am J Kidney Dis 15:458-482, 1990 3. Kopple JD: Effect of nutrition on morbidity and mortality in maintenance dialysis patients. Am J Kidney Dis 24:1002-1009, 1994 4. Bergstro¨m J: Nutrition and mortality in hemodialysis. J Am Soc Nephrol 6:1329-1341, 1995 5. Aparicio M, Cano N, Chauveau P, et al, and the French Study Group for Nutrition in Dialysis: Nutritional status of haemodialysis patients: A French national cooperative study. Nephrol Dial Transplant 14:1679-1686, 1999 6. Corti MC, Guralnik JM, Salive ME, et al: Serum albumin
level and physical disability as predictors of mortality in older persons. JAMA 272:1036-1042, 1994 7. Jebb SA, Elia M: Techniques for the measurement of body composition: A practical guide. Int J Obes 17:611-621, 1993 8. Williams DP, Going SB, Milliken LA, et al: Practical techniques for assessing body composition in middle-aged and older adults. Med Sci Sports Exerc 27:776-783, 1995 9. Chumlea WC, Guo S: Bioelectrical impedance and body composition: Present status and future directions. Nutr Rev 52:123-131, 1994 10. Talluri T, Maggia G: Bioimpedance analysis (BIA) in hemodialysis: Technical aspects. Int J Artif Organs 18:687-692, 1995 11. Bioelectrical impedance analysis in body composition measurement. NIH Technol Assess Statement 1994 Dec 12-14. Am J Clin Nutr 64:524S-532S, 1996 (suppl) 12. Foster KR, Lukaski HC: Whole-body impedance—What does it measure? Am J Clin Nutr 64:388S-396S, 1996 (suppl) 13. Chertow GM, Lowrie EG, Wilmore DW, et al: Nutritional assessment with bioelectrical impedance analysis in maintenance hemodialysis patients. J Am Soc Nephrol 6:75-81, 1995 14. Deurenberg P, Tagliabue A, Schouten FJM: Multifrequency impedance for the prediction of extracellular water and total body water. Br J Nutr 73:349-358, 1995 15. Jabara AE, Mehta RL: Determination of fluid shifts during chronic hemodialysis using bioimpedance spectroscopy and an in-line hematocrit monitor. ASAIO J 41:M682-M687, 1995 16. Biasioli S, Foroni R, Petrosino L, et al: Effect of aging on the body composition of dialyzed subjects. Comparison with normal subjects. ASAIO J 39:M596-M601, 1993 17. Sluys TEMS, van der Ende ME, Swart GR, et al: Body composition in patients with acquired immunodeficiency syndrome: A validation study of bioelectric impedance analysis. JPEN J Parenter Enteral Nutr 17:404-406, 1993 18. Dumler F, Schmidt R, Kilates C, et al: Use of bioelectrical impedance for the nutritional assessment of chronic hemodialysis patients. Miner Electrolyte Metab 18:284-287, 1992 19. Sinning WE, DeOreo PB, Morgan AL, et al: Monitoring hemodialysis changes with bioimpedance. ASAIO J 39:M584M589, 1993 20. Kushner RF, deVries PMJM, Gudivaka R: Use of bioelec-
BIOIMPEDANCE ANALYSIS IN DIALYSIS PATIENTS trical impedance analysis measurements in the clinical management of patients undergoing dialysis. Am J Clin Nutr 64:503S509S, 1996 (suppl) 21. Woodrow G, Oldroyd B, Smith MA, et al: The effect of arteriovenous fistulae in haemodialysis patients on whole body and segmental bioelectrical impedance. Nephrol Dial Transplant 12:524-527, 1997 22. Di Iorio BR, Terracciano V, Bellizzi V: Bioelectrical impedance measurement: Errors and artifacts. J Ren Nutr 9:192-197, 1999 23. Scharfetter H, Monif M, Laszlo Z, et al: Effect of postural changes on the reliability of volume estimations from bioimpedance spectroscopy data. Kidney Int 51:1078-1087, 1997 24. Schmidt R, Dumler F, Cruz C, et al: Improved nutritional follow-up of peritoneal dialysis patients with bioelectrical impedance. Adv Perit Dial 8:157-159, 1992 25. Rallison LR, Kushner RF, Penn D, et al: Errors in estimating peritoneal fluid by bioelectrical impedance analysis and total body electrical conductivity. J Am Coll Nutr 12:66-72, 1993 26. Arkouche W, Fouque D, Pachiaudi C, et al: Total body water and body composition in chronic peritoneal dialysis patients. J Am Soc Nephrol 8:1906-1914, 1997 27. Ho LT, Kushner RF, Schoeller DA, et al: Bioimpedance analysis of total body water in hemodialysis patients. Kidney Int 46:1438-1442, 1994 28. Pastan S, Gassensmith C: Total body water measured by bioelectrical impedance in patients after hemodialysis. Comparison with urea kinetics. ASAIO J 38:M186-M189, 1992 29. Schmidt R, Dumler F, Cruz C: Indirect measures of total body water may confound precise assessment of peritoneal dialysis adequacy. Perit Dial Int 13:S224-S226, 1992 (suppl 2) 30. Zhu F, Schneidtz D, Wang E, et al: Validation of changes in extracellular volume measured during hemodialysis using a segmental bioimpedance technique. ASAIO J 44:M541-M545, 1998 31. Zhu F, Schneidtz D, Levin NW: Sum of segmental bioimpedance analysis during ultrafiltration and hemodialysis reduces sensitivity to changes in body position. Kidney Int 56:692-699, 1999 32. Piccoli A, Rossi B, Pillon L, et al: A new method for monitoring body fluid variation by bioimpedance analysis: The RXc graph. Kidney Int 46:534-539, 1998 33. Piccoli A, Nigrelli S, Caberlotto A, et al: Bivariate normal values of the bioelectrical impedance vector in adult and elderly populations. Am J Clin Nutr 61:269-270, 1995 34. Piccoli A, for the Italian Hemodialysis-Bioelectrical Impedance Analysis (HD-BIA) Study Group: Identification of operational clues to dry weight prescription in hemodialysis using bioimpedance vector analysis. Kidney Int 53:1036-1043, 1998 35. Talluri T, Lietdke RJ, Evangelisti A, et al: Fat-free mass qualitative assessment with bioelectrical impedance analysis (BIA). Ann N Y Acad Sci 873:94-98, 1999 36. Matthie J, Zarowitz B, DeLorenzo A, et al: Analytic assessment of the various bioimpedance methods used to estimate body water. J Appl Physiol 84:1801-1816, 1998 37. Kouw PM, Olthof CG, ter Wee PMK, et al: Assessment of post-dialysis dry weight: An application of the conductivity measurement method. Kidney Int 41:440-444, 1992 38. Fisch BJ, Spiegel DM: Assessment of excess fluid distribution in chronic hemodialysis patients using bioimpedance spectroscopy. Kidney Int 49:1105-1109, 1996
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39. Oe B, De Fijter WM, De Fijter CW, et al: Detection of hydration status by total body bioelectrical impedance analysis (BIA) in patients on hemodialysis. Int J Artif Organs 20:371-374, 1997 40. Zaluska WT, Schneidtz D, Kaufman AM, et al: Relative underestimation of fluid removal during hemodialysis hypotension measured by whole body bioimpedance. ASAIO J 44:823827, 1998 41. Williams DP, Going SB, Milliken LA, et al: Practical techniques for assessing body composition in middle-aged and older adults. Med Sci Sports Exerc 27:776-783, 1995 42. Kotler DP, Burastero S, Wang J, et al: Prediction of body cell mass, fat-free mass, and total body water with bioelectrical impedance analysis: Effects of race, sex and disease. Am J Clin Nutr 64:489S-497S, 1996 (suppl) 43. Houtkooper LB, Lohman TG, Going SB, et al: Why bioelectrical impedance analysis should be used for estimating body adiposity. Am J Clin Nutr 64:436S-448S, 1996 (suppl) 44. Lo WK, Prowant BF, Moore HL, et al: Comparison of different measurements of lean body mass in normal individuals and in chronic peritoneal dialysis patients. Am J Kidney Dis 23:74-85, 1994 45. Stall S, Ginsberg NS, Lynn RI, et al: Bioelectrical impedance analysis and dual energy x-ray absorptiometry to monitor nutritional status. Perit Dial Int 15:S59-S62, 1995 (suppl 5) 46. Woodrow G, Oldroyd B, Turney JH, et al: Measurement of total body water and urea kinetic modeling in peritoneal dialysis. Clin Nephrol 47:52-57, 1997 47. Chertow GM: Estimates of body composition as intermediate outcome variables: Are DEXA and BIA ready for prime time? J Ren Nutr 9:138-141, 1999 48. DeVita MV, Stall SH: Dual-energy X-ray absorptiometry: A review. J Ren Nutr 9:178-181, 1999 49. De Fijter WM, De Fijter CW, Oe PL, et al: Assessment of total body water and lean body mass from anthropometry, Watson formula, creatinine kinetics, and body electrical impedance compared with antipyrine kinetics in peritoneal dialysis patients. Nephrol Dial Transplant 12:151-156, 1997 50. Chertow GM, Lazarus JM, Lew NL, et al: Bioimpedance norms for the hemodialysis population. Kidney Int 52:16171621, 1997 51. Dumler F, Kilates C, Wagner C, et al: Surveillance of nutritional status in chronic dialysis patients. J Ren Nutr 7:194198, 1997 52. Dumler F, Falla P, Butler R, et al: Impact of dialysis modality and acidosis on nutritional status. ASAIO J 45:413-417, 1999 53. Pencharz PB, Azcue M: Use of bioelectrical impedance analysis measurements in the clinical management of malnutrition. Am J Clin Nutr 64:485S-488S, 1996 (suppl) 54. Hu HY, Kato Y: Body composition assessed by bioelectrical impedance analysis (BIA) in patients with Graves’ disease before and after treatment. Endocr J 42:545-550, 1995 55. Seppel T, Kosel A, Schlaghecke R: Bioelectrical impedance assessment of body composition in thyroid disease. Eur J Endocrinol 136:493-498, 1997 56. Beshyah SA, Freemantle C, Thomas E, et al: Comparison of measurement sof body composition by total body potassium, bioimpedance analysis, and dual-energy x-ray absorptiometry in hypopituitary adults before and during growth hormone treatment. Am J Clin Nutr 61:1186-1194, 1995
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57. de Boer H, Blok GJ, Voerman B, et al: The optimal growth hormone replacement dose in adults, derived from bioimpedance analysis. J Clin Endocrinol Metab 80:2069-2076, 1995 58. Briganti M, Emiliani G, Montanari A, et al: Longitudinal assessment of body composition in CAPD patients using bioelectric impedance analysis. A comparison with hemodialysis patients. ASAIO J 41:M725-M727, 1995 59. Johannsson G, Bengtsson B-A, Ahlme´n J: Double-blind, placebo-controlled study of growth hormone treatment in elderly patients undergoing chronic hemodialysis: Anabolic effect and functional improvement. Am J Kidney Dis 33:709-717, 1999 60. Bergia R, Bellini ME, Valenti M, et al: Longitudinal assessment of body composition in continuous ambulatory peritoneal dialysis patients using bioelectric impedance and anthropometric measurements. Perit Dial Int 13:S512-S514, 1993 (suppl 2) 61. Chertow GM, Laqarux JM, Lew NL, et al: Development
of a population-specific regression equation to estimate total body water in hemodialysis patients. Kidney Int 51:1578-1582, 1997 62. Lukaski H: Validation of body composition assessment techniques in the dialysis population. ASAIO J 43:251-255, 1997 63. Fisch BJ, Spiegel DM: Assessment of excess fluid distribution in chronic hemodialysis patients using bioimpedance spectroscopy. Kidney Int 49:1105-1109, 1996 64. Ott M, Fischer H, Polat H, et al: Bioelectrical impedance analysis as a predictor of survival in patients with human immunodeficiency virus infection. J Acquir Immune Defic Syndr 9:20-25, 1995 65. Maggiore Q, Nigrelli S, Ciccarelli C, et al: Nutritional and prognostic correlates of bioimpedance indexes in hemodialysis patients. Kidney Int 50:2103-2108, 1996 66. Chertow GM, Jacobs DO, Lazarus JM, et al: Phase angle predicts survival in hemodialysis patients. J Ren Nutr 7:204-207, 1997
Use of Bioelectrical Impedance Techniques for Monitoring Nutritional Status in Patients on Maintenance Dialysis Francis Dumler, MD,* and Cristina Kilates, RD, MS† Malnutrition continues to be an important correlate of survival in dialysis patients. Nutritional surveillance at the clinical level requires use of simple, reasonably accurate, and easily accessible techniques for multicompartmental body composition analysis. Unfortunately, although gold standard methodologies (body density by underwater weight, total body water by isotope dilution, bone mineral content by neutron activation, total body potassium by 40K whole body gamma counting) provide very precise assessments, they are not applicable to routine clinical practice. Because of its availability and simplicity, bioelectrical impedance (BEI) has significant potential as a complement to standard anthropometric techniques in the nutritional monitoring of patients with chronic renal failure. Consistency of technique and standardization of BEI equipment are essential for reproducibility of results. Several studies have validated the use of total body water by BEI as a surrogate for isotope dilution methods in dialysis patients, whereas others have established an excellent correlation with the volume of distribution of urea as measured by urea kinetic volume. Bioimpedance analysis for measurement of lean body mass has been extensively evaluated in stable healthy populations, with results similar to those obtained using hydrodensitometry and total body potassium. In dialysis patients, accuracy is contingent on a stable hydration status and/or appropriate correction for changes in extracellular volume status over time. Recent publication of bioimpedance norms for the hemodialysis population allows better comparisons with the national reference population studied as part of the National Health and Nutrition Examination Survey III (US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics, Hyattsville, MD). BEI methodology is a practical bedside tool for assessment of body composition that provides more consistent and reproducible results than standard anthropometry alone. r 2000 by the National Kidney Foundation, Inc.
T
*Chief, Division of Nephrology, William Beaumont Hospital, Royal Oak, MI, and Clinical Professor of Internal Medicine, Wayne State University, Detroit, MI. †Renal Research Dietitian, Division of Nephrology, Henry Ford Hospital, Detroit, MI. Address reprint requests to Francis Dumler, MD, Division of Nephrology, William Beaumont Hospital, 3535 W 13 Mile Rd, Suite #642, Royal Oak, MI 48073-6705. r 2000 by the National Kidney Foundation, Inc. 1051-2276/00/1003-0002$3.00/0 doi:10.1053/jren.2000.7916
also assumed that maintenance dialysis therapy would be too risky for diabetics patients and the elderly, thereby resulting in premature death. Of note in this regard, the most recent data from the United States Renal Data System shows the highest increase in ESRD (1988 to 1997) among the elderly (80⫹ years: 277%; 70-79 years: 160%). As a comparison, the corresponding figure for those younger than age 60 is 73%. In addition, diabetes accounted for the greatest increment (180%) in ESRD, followed by hypertension (86%) and glomerulonephritis (37%). These demographic changes place the current ESRD patient population at a very high risk for malnutrition because of associated multiple comorbid illnesses.1 In spite of continuous advances in dialytic
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Journal of Renal Nutrition, Vol 10, No 3 ( July), 2000: pp 116-124
HE END-STAGE renal disease (ESRD) program was initially envisioned as part of a disease management strategy that would sustain life and improve health, allowing patients to eventually return to work and continue contributing to society. That initiative
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therapy and improvements in the management of cardiovascular disease and infections, mortality in the dialysis population continues to be unusually high. Inadequate nutrition has been clearly identified as a significant risk factor for survival, and affecting 30% to 70% of patients.2-5 Unfortunately, very few registries have recorded nutritional status on a regular basis. Hypoalbuminemia is another substantial marker for increased morbidity and mortality in dialysis patients. In the elderly, hypoalbuminemia is a risk factor even in individuals with normal renal function.6 Early recognition of malnutrition, implementation of nutritional interventional strategies, and longitudinal monitoring of body composition are intuitively necessary for the appropriate management of dialysis patients. Unfortunately, current methods for nutritional analysis, when applied to the clinical setting, are time-consuming, impractical, nonspecific, or affected by the metabolic disturbances associated with uremia. Classic body composition analysis defines constituents as fat or fat-free. The former is a fairly homogenous compartment, whereas the latter includes water, protein, bone, and small amounts of various components such a glycogen. Several methods are available for independent assessment of these individual components. Estimates using these multiple compartmental models are independent of assumed numerical relationships between components.7,8 Unfortunately, although body density by underwater weight and residual lung volume, total body water by isotope dilution, bone mineral content by neutron activation, and total body potassium by gamma counting measurements will provide a very accurate multicompartmental analysis of body composition, they are not applicable to routine clinical patient care. From a utilitarian perspective, body composition analysis methods can be categorized as reference (whole body density, isotope dilution, total body potassium, in-vivo neutron activation), bedside (anthropometry, bioelectrical impedance [BEI], near infra-red interactance), and intermediate (dual energy x-ray absorptiometry [DEXA]). Because of their simplicity and availability, anthropometry and bioelectrical impedance have received significant attention from the renal community.
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BEI Analysis Charged ions within a cell and its surrounding fluid are unevenly distributed across the membrane wall. The potential difference of about 100 mV is a result of the lag of Cl⫺ ions during K⫹ extrusion. Cell membranes consist of a layer of nonconductive lipophilic material interposed between 2 layers of conductive protein molecules. This structure makes cells behave as capacitors (objects capable of storing electrical charge) when exposed to an electric current, with the cell membrane acting as the dielectric insulating material.9-12 Mammalian tissues conduct an electrical current in proportion to their water and electrolyte content. Body fluids and electrolytes, mostly contained in lean tissues, have highly conductive, low resistance electrical pathways. Skin, fat, and bone are poor conductors and offer a high resistance. This tissue-specific resistance is measured by the voltage drop between 2 points. Reactance is the opposition to the flow of electric current caused by the electrical charge stored in the cell membrane. Only cell membranes offer reactance to electrical current.9-12 In the human body, the resistance and reactance components are aligned in both parallel and series orientations, with the vectorial components of impedance directly measured as resistance and reactance. Extracellular and intracellular fluid content defines the former, and the cell membrane the latter. In fat-free mass, these fluid compartments are in reality parallel fluid moieties separated by cell membranes; therefore, their impedance vector is more accurately determined with parallel models. Although arms and legs only account for 35% of total body volume, they represent approximately 85% of total body resistance.9-12 Very low frequency currents pass only through the extracellular fluid, whereas high frequency currents traverse both intracellular and extracellular paths. During single frequency BEI analysis, a small current (typically 800 µA, usually at a frequency of 50 kHz) is passed through the body over a 2-minute period. The instrument measures the resulting voltage produced between 2 electrodes. The impedance (Z) is mathematically calculated from the resistance (R) and reactance (Xc) vectors (Z2 ⫽ R2 ⫹ Xc2). The phase angle
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(arctangence of the ratio of reactance to resistance) is an index of cell membrane integrity and is particularly influenced by cellular metabolic function.13 In multifrequency BEI, the relationship between resistance and reactance is analyzed over a wide spectrum of frequencies (at least 100). At very low frequencies, the reactance is zero and measured impedance is all resistance. As the frequency rises, reactance increases, causing the phase angle to open until a maximum is reached in which all impedance is reactance. The mathematics describing these events is known as the Cole-Cole function and allows estimation of intracellular and extracellular body water.14,15 These complex profiles are influenced by cell size, membrane permeability, intracellular composition, and distribution of body fluids (which affects the amount of current shunting through interstitial spaces). Single frequency bioimpedance analysis has been used to calculate total body water, fat-free mass, and, more recently, body cell mass. This latter parameter is inclusive of total protein and intracellular water, and is considered the most metabolically active body compartment.13,16 Body cell mass quantitation by BEI closely correlates with those using measured exchangeable sodium and derived exchangeable potassium.17
Impact of Dialysis on BEI Measurements of Resistance and Reactance Several hemodialysis-related factors impact resistance and reactance measurements. Patientspecific variables include location of the hemodialysis access and body position at the time of assessment. Hemodialysis-related parameters relate to solute removal and degree of ultrafiltration. Studies conducted using continuous BEI monitoring during the entire hemodialysis procedure show a gradual and consistent increase in resistance, which reaches a plateau value at 150 minutes into dialysis. This change is present during dialysis regardless of fluid removal.18,19 Actually, the greatest increases are observed with pure ultrafiltration, whereas the least change is noted when hemodialysis is performed alone without ultrafiltration. Intermediate increases are noted during hemodialysis with fluid removal, as
is usual in the clinical setting.18 These changes are multifactorial and related to increases in specific resistance of body fluids, a rising hematocrit, changes in solute concentration, a varying distribution of intracellular and extracellular water and electrolytes, and loss of total body water.20 In our experience, resistance readings using the extremity with a functioning arteriovenous access for hemodialysis are consistently 10% lower than when using the controlateral limb. In addition, the dominant side also has higher resistance values. Others have found similar results.21,22 Differences in types of vascular access and use of dominant versus nondominant limbs can influence results and increase variability. We have found no clinical differences in resistance measurements in dialysis patients taken in the lying and sitting position. In healthy subjects, resistance measurements taken in the supine position are on average 2% higher than in the seated position.23 Finally, the presence of a central hemodialysis catheter may result in resistance readings 9% lower than in the controlateral side.22 No changes in resistance are observed in peritoneal dialysis patients after infusion or drainage of dialysate.24-26 This is related to slow solute and fluid mass transfer, and to the low contribution of the abdominal cavity (⬍10%) to total body resistance. Actually, BEI analysis does not detect fluid in the abdominal cavity, whether it is ascitis or dialysate.24-26 When using BEI analysis in the clinical setting, it is very important to pay attention to detail to minimize intra- and inter-patient variability. During longitudinal observation, absolute values are not as critical as detecting changes. But, the greater methodological variability, the lesser the sensitivity of the measurement. In our programs, we adhere to a strict protocol aimed at minimizing technical variability. All patients are evaluated 15 minutes after completion of hemodialysis, using the nonaccess side, in a sitting position with the back at 30° from the vertical, and with the footrest elevated. Limbs are placed at a 30° abduction. Continuous ambulatory peritoneal dialysis patients are measured in a similar manner during a regular clinic visit. Every effort is made to perform the study when patients are clinically at dry weight. All measurements and data analysis are performed under the direct supervision of our renal dietitians.
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Assessment of Body Composition Analysis by BEI Nutritional status optimization is essential to the care of dialysis patients. The need for prospective evaluation of body composition is a key element in achieving this goal. Assessment of total body water, lean body mass, fat mass, and body cell mass over time is of clinical importance to facilitate definition of dry weight adequacy and to identify individuals at particular risk for malnutrition. Several authors have validated the use of total body water by BEI as a surrogate for isotope dilution methods in dialysis patients,13,27 whereas others have established an excellent correlation with the volume of distribution of urea as measured by urea kinetic volume.28,29 It is important to note that although total body water estimates by BEI have the smallest bias and the best correlation with isotope quantitation, individual variations may be high enough to warrant more specific approaches. Some have suggested the use of segmental bioimpedance analysis for more accurate evaluation of rapid fluid changes, as this technique is more sensitive to fluctuations in the central (trunk) volume than whole body bioimpedance.30,31 Another recent approach is to define the state of hydration by using the bioimpedance vector analysis technique.32-34 Rather than calculating total body water from the bioimpedance measurements, this method plots resistance and reactance values factored by height, and defines the value and angle of the bioimpedance vector. An important benefit of using this direct measurement is the elimination of bias related to the use of population-derived constants and functions in the calculations. Another major advantage of vector analysis is the ability to identify the hydration status of an individual patient within 75% to 95% confidence ellipses predefined in a reference normal population. Single frequency BEI estimates intracellular and extracellular volumes by using derivative equations based on the phase angle relationship between reactance and resistance,10,13,35 whereas multifrequency BEI spectroscopy provides a more direct assessment of intracellular and extracellular volume.36 In general, overhydration in dialysis patients is mostly caused by increases in extracellu-
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lar rather than intracellular volume.27,37-39 In addition, most studies suggest that ultrafiltration during hemodialysis is primarily at the expense of the extracellular compartment. During hypotension, fluid is predominantly removed from the central compartment (trunk and central blood volume), with limb fluid volume remaining fairly stable.40 Assessment of lean body mass by BEI analysis has been extensively validated in stable healthy populations, with results similar to those obtained with hydrodensitometry and total body potassium.9,11,41-43 Transformation of resistance and reactance values from a series to a parallel model increases the accuracy of lean body mass estimates, as muscle mass is in reality composed of cells surrounded by interstitial fluid.10,12,42 Several studies in dialysis patients have compared lean body mass measurements by BEI with those obtained using dual energy x-ray absorptiometry. Although the number of patients studied is relatively small, there is a high degree of correlation and concordance between these 2 methods.13,41,44-46 Most important, both BEI and DEXA are influenced by the degree of tissue hydration.47,48 In edematous patients, excess water, exclusive to the extracellular compartment, alters the balance between intracellular and extracellular volumes. BEI equations using weight as a variable will apportion some of this excess fluid to the intracellular compartment, thereby falsely increasing lean body mass. The Deurenberg equation, which does not include the term weight, may provide some advantage in patients believed to be volume overloaded.49 Most studies of body composition in dialysis patients have been cross-sectional.13,16,18,24,26 This approach has been used to define quartiles for the hemodialysis population.50 Although no such reference data is available for peritoneal dialysis patients, we have found no differences in body composition between hemodialysis and peritoneal dialysis.51,52 Therefore, it is reasonable at present to use hemodialysis standards for all dialysis patients. Of greater significance, the recently completed National Health and Nutrition Examination Survey III (data available in CDROM format from US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics,
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Hyattsville, MD 20782-2003) survey has used BEI analysis to define general population norms. This provides a unique opportunity for evaluating the bioimpedance data in dialysis patients in relation to normative data from the general population that is specific for age, race, and gender. Most important is the potential for longitudinal follow-up of patients at risk for malnutrition. Several studies have reported on the use of BEI on interventional studies of malnutrition in nonrenal disease. In a refeeding study of malnourished patients, BEI predicted changes in body composition with greater prediction than anthropometry.53 In hyperthyroid patients, BEI has been used to evaluate lean body mass content before and after treatment.54,55 Bioimpedance techniques have also been used in the monitoring of hypopituitary patients treated with recombinant growth hormone.56,57 In chronic renal failure patients, decreases in body weight may not correlate with changes in lean body mass as measured by BEI, particularly when physical inactivity, fluid retention, and fat tissue increases are concurrent to muscle mass loss. In a previous study, 28% of hemodialysis patients lost body weight, whereas a decrease in lean body mass was identified in 41% of patients. In addition, only 3% of patients showed no change in lean body mass, whereas body weight remained neutral in 28% during a 12-month observation period.18 In peritoneal dialysis patients, serial BEI assessments identified a decrease in body weight in 36% of patients, whereas a loss of lean body mass was noted in 49%. Actually, among the 64% of patients with increasing body weights, BEI showed an actual loss of lean body mass in 24%.24 Others have reported similar increases in body weight caused by fat mass accumulation.58 A very recent study has evaluated lean body mass changes over a 6-month period in hemodialysis patients treated thrice weekly with recombinant growth hormone. Although there were no changes in body mass index, lean body mass by BEI increased by a mean of 3.9 kg, whereas in the placebo group it suffered a 1.2-kg decrease.59 Longitudinal body composition analysis using current BEI or DEXA techniques has the risk of interpreting an increase in total body water (overhydration) as lean body mass.60 Population-
specific equations currently developed for ESRD patients will yield superior predictive power, thereby minimizing longitudinal variability.61 Technologically advanced systems allowing separate evaluation of intracellular fluid and body cell mass will greatly facilitate assessment of body composition analysis in patients with abnormal water distribution.62,63 Body cell mass represents the active metabolic component of the body and encompasses all intracellular tissues and extracellular protein. The gold standard techniques for body cell mass measurements are neutron activation and total body potassium. It is clinically estimated by DEXA and BEI, with the latter systematically underestimating values by 19% relative to the former.13 Because of difficulties with tissue hydration and mathematical derivations to define body compartments, some authors have evaluated the relationship between direct impedance measurements and patient outcomes. The phase angle, a direct measure of cellular health and stability that reflects the extracellular to intracellular water ratio, can be conceptualized as a BEI summation value. Of interest, a variety of studies have shown the phase angle to be a significant predictor for survival in patients with acquired immunodeficiency syndrome and in patients with ESRD.64-66 These observations strongly suggest that use of phase angle, a powerful predictor of mortality, may become critical in the identification of individuals at particular risk who may benefit from intense scrutiny leading to optimization of therapies. In summary, BEI assessments of body composition in dialysis patients require attention to detail to minimize technique variability. The clinical experience with single frequency impedance analysis is greater than with multifrequency techniques. Factors to consider include hydration status, body position, hemodialysis access, and timing of measurements in relation to the dialysis procedure. Consistency of technique and standardization of BEI equipment are essential for reproducibility of results. Equations used in calculations must be age-, sex-, race-, body habitus–, and populationspecific whenever possible. Impedance vector analysis and phase angle are promising new applications that merit significant consideration in clinical practice.
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Appendix 1. Compilation of References Listed in This Review That Report on Bioelectrical Impedance Analysis Specific to the End-Stage Renal Disease Population 1. Talluri T, Maggia G: Bioimpedance analysis (BIA) in hemodialysis: Technical aspects. Int J Artif Organs 18:687-692, 1995 2. Chertow GM, Lowrie EG, Wilmore DW, et al: Nutritional assessment with bioelectrical impedance analysis in maintenance hemodialysis patients. J Am Soc Nephrol 6:75-81, 1995 3. Jabara AE, Mehta RL: Determination of fluid shifts during chronic hemodialysis using bioimpedance spectroscopy and an in-line hematocrit monitor. ASAIO J 41:M682-M687, 1995 4. Biasioli S, Foroni R, Petrosino L, et al: Effect of aging on the body composition of dialyzed subjects. Comparison with normal subjects. ASAIO J 39:M596-M601, 1993 5. Dumler F, Schmidt R, Kilates C, et al: Use of bioelectrical impedance for the nutritional assessment of chronic hemodialysis patients. Miner Electrolyte Metab 18:284-287, 1992 6. Sinning WE, DeOreo PB, Morgan AL, et al: Monitoring hemodialysis changes with bioimpedance. ASAIO J 39:M584M589, 1993 7. Kushner RF, deVries PMJM, Gudivaka R: Use of bioelectrical impedance analysis measurements in the clinical management of patients undergoing dialysis. Am J Clin Nutr 64:503S-509S, 1996 (suppl) 8. Woodrow G, Oldroyd B, Smith MA, et al: The effect of arteriovenous fistulae in haemodialysis patients on whole body and segmental bioelectrical impedance. Nephrol Dial Transplant 12:524-527, 1997 9. Di Iorio BR, Terracciano V, Bellizzi V: Bioelectrical impedance measurement: Errors and artifacts. J Ren Nutr 9:192197, 1999 10. Schmidt R, Dumler F, Cruz C, et al: Improved nutritional follow-up of peritoneal dialysis patients with bioelectrical impedance. Adv Perit Dial 8:157-159, 1992 11. Rallison LR, Kushner RF, Penn D, et al: Errors in estimating peritoneal fluid by bioelectrical impedance analysis and total body electrical conductivity. J Am Coll Nutr 12:66-72, 1993 12. Arkouche W, Fouque D, Pachiaudi C, et al: Total body water and body composition in chronic peritoneal dialysis patients. J Am Soc Nephrol 8:1906-1914, 1997 13. Ho LT, Kushner RF, Schoeller DA, et al: Bioimpedance analysis of total body water in hemodialysis patients. Kidney Int 46:1438-1442, 1994 14. Pastan S, Gassensmith C: Total body water measured by bioelectrical impedance in patients after hemodialysis. Comparison with urea kinetics. ASAIO J 38:M186-M189, 1992 15. Schmidt R, Dumler F, Cruz C: Indirect measures of total body water may confound precise assessment of peritoneal dialysis adequacy. Perit Dial Int 13:S224-S226, 1992 16. Zhu F, Schneidtz D, Wang E, et al: Validation of changes in extracellular volume measured during hemodialysis using a segmental bioimpedance technique. ASAIO J 44:M541-M545, 1998 17. Zhu F, Schneidtz D, Levin NW: Sum of segmental bioimpedance analysis during ultrafiltration and hemodialysis reduces sensitivity to changes in body position. Kidney Int 56:692-699, 1999 18. Piccoli A, for the Italian Hemodialysis-Bioelectrical Impedance Analysis (HD-BIA) Study Group: Identification of operational clues to dry weight prescription in hemodialysis using bioimpedance vector analysis. Kidney Int 53:10361043, 1998 19. Kouw PM, Olthof CG, ter Wee PMK, et al: Assessment of post-dialysis dry weight: An application of the conductivity measurement method. Kidney Int 41:440-444, 1992 20. Fisch BJ, Spiegel DM: Assessment of excess fluid distribution in chronic hemodialysis patients using bioimpedance spectroscopy. Kidney Int 49:1105-1109, 1996 21. Oe B, De Fijter WM, De Fijter CW, et al: Detection of hydration status by total body bioelectrical impedance analysis (BIA) in patients on hemodialysis. Int J Artif Organs 20:371-374, 1997 22. Zaluska WT, Schneidtz D, Kaufman AM, et al: Relative underestimation of fluid removal during hemodialysis hypotension measured by whole body bioimpedance. ASAIO J 44:823-827, 1998 23. Kotler DP, Burastero S, Wang J, et al: Prediction of body cell mass, fat-free mass, and total body water with bioelectrical impedance analysis: Effects of race, sex and disease. Am J Clin Nutr 64:489S-497S, 1996 (suppl) 24. Lo WK, Prowant BF, Moore HL, et al: Comparison of different measurements of lean body mass in normal individuals and in chronic peritoneal dialysis patients. Am J Kidney Dis 23:74-85, 1994 25. Woodrow G, Oldroyd B, Turney JH, et al: Measurement of total body water and urea kinetic modeling in peritoneal dialysis. Clin Nephrol 47:52-57, 1997 26. De Fijter WM, De Fijter CW, Oe PL, et al: Assessment of total body water and lean body mass from anthropometry, Watson formula, creatinine kinetics, and body electrical impedance compared with antipyrine kinetics in peritoneal dialysis patients. Nephrol Dial Transplant 12:151-156, 1997 27. Chertow GM, Lazarus JM, Lew NL, et al: Bioimpedance norms for the hemodialysis population. Kidney Int 52:16171621, 1997 28. Dumler F, Kilates C, Wagner C, et al: Surveillance of nutritional status in chronic dialysis patients. J Ren Nutr 7:194198, 1997 29. Dumler F, Falla P, Butler R, et al: Impact of dialysis modality and acidosis on nutritional status. ASAIO J 45:413-417, 1999
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Appendix 1. Compilation of References Listed in This Review That Report on Bioelectrical Impedance Analysis Specific to the End-Stage Renal Disease Population (Cont’d) 30. Briganti M, Emiliani G, Montanari A, et al: Longitudinal assessment of body composition in CAPD patients using bioelectric impedance analysis. A comparison with hemodialysis patients. ASAIO J 41:M725-M727, 1995 31. Johannsson G, Bengtsson B-A, Ahlme´n J: Double-blind, placebo-controlled study of growth hormone treatment in elderly patients undergoing chronic hemodialysis: Anabolic effect and functional improvement. Am J Kidney Dis 33:709-717, 1999 32. Bergia R, Bellini ME, Valenti M, et al: Longitudinal assessment of body composition in continuous ambulatory peritoneal dialysis patients using bioelectric impedance and anthropometric measurements. Perit Dial Int 13:S512-S514, 1993 (suppl 2) 33. Chertow GM, Laqarux JM, Lew NL, et al: Development of a population-specific regression equation to estimate total body water in hemodialysis patients. Kidney Int 51:1578-1582, 1997 34. Fisch BJ, Spiegel DM: Assessment of excess fluid distribution in chronic hemodialysis patients using bioimpedance spectroscopy. Kidney Int 49:1105-1109, 1996 35. Maggiore Q, Nigrelli S, Ciccarelli C, et al: Nutritional and prognostic correlates of bioimpedance indexes in hemodialysis patients. Kidney Int 50:2103-2108, 1996 36. Chertow GM, Jacobs DO, Lazarus JM, et al: Phase angle predicts survival in hemodialysis patients. J Ren Nutr 7:204-207, 1997
Appendix 2. Advantages and Disadvantages of Bioelectrical Impedance Analysis in the Clinical Evaluation of Chronic Renal Failure Patients Advantages
Disadvantages
ⴱ Small coefficient of variation for direct measurements ⴱ Easy technique to use and very practical in a clinic setting ⴱ Accurate and reproducible estimate of total body water ⴱ Better predictor of changes in body composition than anthropometry ⴱ Established bioelectrical impedance norms in the general population and hemodialysis patients
ⴱ Equipment calibration and method standardization are prerequisites ⴱ Lean body mass and fat mass measurements are influenced by the state of overhydration ⴱ Standard single frequency techniques do not detect fluid changes in the thoracoabdominal cavity ⴱ Technique not validated in amputees
References 1. U.S. Renal Data System, USRDS 1998 Annual Report. Bethesda, MD, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, April 1998 2. Lowrie EG, Lew NL: Death risk in hemodialysis patients: The predictive value of commonly measured variables and an evaluation of death rate differences between facilities. Am J Kidney Dis 15:458-482, 1990 3. Kopple JD: Effect of nutrition on morbidity and mortality in maintenance dialysis patients. Am J Kidney Dis 24:1002-1009, 1994 4. Bergstro¨m J: Nutrition and mortality in hemodialysis. J Am Soc Nephrol 6:1329-1341, 1995 5. Aparicio M, Cano N, Chauveau P, et al, and the French Study Group for Nutrition in Dialysis: Nutritional status of haemodialysis patients: A French national cooperative study. Nephrol Dial Transplant 14:1679-1686, 1999 6. Corti MC, Guralnik JM, Salive ME, et al: Serum albumin
level and physical disability as predictors of mortality in older persons. JAMA 272:1036-1042, 1994 7. Jebb SA, Elia M: Techniques for the measurement of body composition: A practical guide. Int J Obes 17:611-621, 1993 8. Williams DP, Going SB, Milliken LA, et al: Practical techniques for assessing body composition in middle-aged and older adults. Med Sci Sports Exerc 27:776-783, 1995 9. Chumlea WC, Guo S: Bioelectrical impedance and body composition: Present status and future directions. Nutr Rev 52:123-131, 1994 10. Talluri T, Maggia G: Bioimpedance analysis (BIA) in hemodialysis: Technical aspects. Int J Artif Organs 18:687-692, 1995 11. Bioelectrical impedance analysis in body composition measurement. NIH Technol Assess Statement 1994 Dec 12-14. Am J Clin Nutr 64:524S-532S, 1996 (suppl) 12. Foster KR, Lukaski HC: Whole-body impedance—What does it measure? Am J Clin Nutr 64:388S-396S, 1996 (suppl) 13. Chertow GM, Lowrie EG, Wilmore DW, et al: Nutritional assessment with bioelectrical impedance analysis in maintenance hemodialysis patients. J Am Soc Nephrol 6:75-81, 1995 14. Deurenberg P, Tagliabue A, Schouten FJM: Multifrequency impedance for the prediction of extracellular water and total body water. Br J Nutr 73:349-358, 1995 15. Jabara AE, Mehta RL: Determination of fluid shifts during chronic hemodialysis using bioimpedance spectroscopy and an in-line hematocrit monitor. ASAIO J 41:M682-M687, 1995 16. Biasioli S, Foroni R, Petrosino L, et al: Effect of aging on the body composition of dialyzed subjects. Comparison with normal subjects. ASAIO J 39:M596-M601, 1993 17. Sluys TEMS, van der Ende ME, Swart GR, et al: Body composition in patients with acquired immunodeficiency syndrome: A validation study of bioelectric impedance analysis. JPEN J Parenter Enteral Nutr 17:404-406, 1993 18. Dumler F, Schmidt R, Kilates C, et al: Use of bioelectrical impedance for the nutritional assessment of chronic hemodialysis patients. Miner Electrolyte Metab 18:284-287, 1992 19. Sinning WE, DeOreo PB, Morgan AL, et al: Monitoring hemodialysis changes with bioimpedance. ASAIO J 39:M584M589, 1993 20. Kushner RF, deVries PMJM, Gudivaka R: Use of bioelec-
BIOIMPEDANCE ANALYSIS IN DIALYSIS PATIENTS trical impedance analysis measurements in the clinical management of patients undergoing dialysis. Am J Clin Nutr 64:503S509S, 1996 (suppl) 21. Woodrow G, Oldroyd B, Smith MA, et al: The effect of arteriovenous fistulae in haemodialysis patients on whole body and segmental bioelectrical impedance. Nephrol Dial Transplant 12:524-527, 1997 22. Di Iorio BR, Terracciano V, Bellizzi V: Bioelectrical impedance measurement: Errors and artifacts. J Ren Nutr 9:192-197, 1999 23. Scharfetter H, Monif M, Laszlo Z, et al: Effect of postural changes on the reliability of volume estimations from bioimpedance spectroscopy data. Kidney Int 51:1078-1087, 1997 24. Schmidt R, Dumler F, Cruz C, et al: Improved nutritional follow-up of peritoneal dialysis patients with bioelectrical impedance. Adv Perit Dial 8:157-159, 1992 25. Rallison LR, Kushner RF, Penn D, et al: Errors in estimating peritoneal fluid by bioelectrical impedance analysis and total body electrical conductivity. J Am Coll Nutr 12:66-72, 1993 26. Arkouche W, Fouque D, Pachiaudi C, et al: Total body water and body composition in chronic peritoneal dialysis patients. J Am Soc Nephrol 8:1906-1914, 1997 27. Ho LT, Kushner RF, Schoeller DA, et al: Bioimpedance analysis of total body water in hemodialysis patients. Kidney Int 46:1438-1442, 1994 28. Pastan S, Gassensmith C: Total body water measured by bioelectrical impedance in patients after hemodialysis. Comparison with urea kinetics. ASAIO J 38:M186-M189, 1992 29. Schmidt R, Dumler F, Cruz C: Indirect measures of total body water may confound precise assessment of peritoneal dialysis adequacy. Perit Dial Int 13:S224-S226, 1992 (suppl 2) 30. Zhu F, Schneidtz D, Wang E, et al: Validation of changes in extracellular volume measured during hemodialysis using a segmental bioimpedance technique. ASAIO J 44:M541-M545, 1998 31. Zhu F, Schneidtz D, Levin NW: Sum of segmental bioimpedance analysis during ultrafiltration and hemodialysis reduces sensitivity to changes in body position. Kidney Int 56:692-699, 1999 32. Piccoli A, Rossi B, Pillon L, et al: A new method for monitoring body fluid variation by bioimpedance analysis: The RXc graph. Kidney Int 46:534-539, 1998 33. Piccoli A, Nigrelli S, Caberlotto A, et al: Bivariate normal values of the bioelectrical impedance vector in adult and elderly populations. Am J Clin Nutr 61:269-270, 1995 34. Piccoli A, for the Italian Hemodialysis-Bioelectrical Impedance Analysis (HD-BIA) Study Group: Identification of operational clues to dry weight prescription in hemodialysis using bioimpedance vector analysis. Kidney Int 53:1036-1043, 1998 35. Talluri T, Lietdke RJ, Evangelisti A, et al: Fat-free mass qualitative assessment with bioelectrical impedance analysis (BIA). Ann N Y Acad Sci 873:94-98, 1999 36. Matthie J, Zarowitz B, DeLorenzo A, et al: Analytic assessment of the various bioimpedance methods used to estimate body water. J Appl Physiol 84:1801-1816, 1998 37. Kouw PM, Olthof CG, ter Wee PMK, et al: Assessment of post-dialysis dry weight: An application of the conductivity measurement method. Kidney Int 41:440-444, 1992 38. Fisch BJ, Spiegel DM: Assessment of excess fluid distribution in chronic hemodialysis patients using bioimpedance spectroscopy. Kidney Int 49:1105-1109, 1996
123
39. Oe B, De Fijter WM, De Fijter CW, et al: Detection of hydration status by total body bioelectrical impedance analysis (BIA) in patients on hemodialysis. Int J Artif Organs 20:371-374, 1997 40. Zaluska WT, Schneidtz D, Kaufman AM, et al: Relative underestimation of fluid removal during hemodialysis hypotension measured by whole body bioimpedance. ASAIO J 44:823827, 1998 41. Williams DP, Going SB, Milliken LA, et al: Practical techniques for assessing body composition in middle-aged and older adults. Med Sci Sports Exerc 27:776-783, 1995 42. Kotler DP, Burastero S, Wang J, et al: Prediction of body cell mass, fat-free mass, and total body water with bioelectrical impedance analysis: Effects of race, sex and disease. Am J Clin Nutr 64:489S-497S, 1996 (suppl) 43. Houtkooper LB, Lohman TG, Going SB, et al: Why bioelectrical impedance analysis should be used for estimating body adiposity. Am J Clin Nutr 64:436S-448S, 1996 (suppl) 44. Lo WK, Prowant BF, Moore HL, et al: Comparison of different measurements of lean body mass in normal individuals and in chronic peritoneal dialysis patients. Am J Kidney Dis 23:74-85, 1994 45. Stall S, Ginsberg NS, Lynn RI, et al: Bioelectrical impedance analysis and dual energy x-ray absorptiometry to monitor nutritional status. Perit Dial Int 15:S59-S62, 1995 (suppl 5) 46. Woodrow G, Oldroyd B, Turney JH, et al: Measurement of total body water and urea kinetic modeling in peritoneal dialysis. Clin Nephrol 47:52-57, 1997 47. Chertow GM: Estimates of body composition as intermediate outcome variables: Are DEXA and BIA ready for prime time? J Ren Nutr 9:138-141, 1999 48. DeVita MV, Stall SH: Dual-energy X-ray absorptiometry: A review. J Ren Nutr 9:178-181, 1999 49. De Fijter WM, De Fijter CW, Oe PL, et al: Assessment of total body water and lean body mass from anthropometry, Watson formula, creatinine kinetics, and body electrical impedance compared with antipyrine kinetics in peritoneal dialysis patients. Nephrol Dial Transplant 12:151-156, 1997 50. Chertow GM, Lazarus JM, Lew NL, et al: Bioimpedance norms for the hemodialysis population. Kidney Int 52:16171621, 1997 51. Dumler F, Kilates C, Wagner C, et al: Surveillance of nutritional status in chronic dialysis patients. J Ren Nutr 7:194198, 1997 52. Dumler F, Falla P, Butler R, et al: Impact of dialysis modality and acidosis on nutritional status. ASAIO J 45:413-417, 1999 53. Pencharz PB, Azcue M: Use of bioelectrical impedance analysis measurements in the clinical management of malnutrition. Am J Clin Nutr 64:485S-488S, 1996 (suppl) 54. Hu HY, Kato Y: Body composition assessed by bioelectrical impedance analysis (BIA) in patients with Graves’ disease before and after treatment. Endocr J 42:545-550, 1995 55. Seppel T, Kosel A, Schlaghecke R: Bioelectrical impedance assessment of body composition in thyroid disease. Eur J Endocrinol 136:493-498, 1997 56. Beshyah SA, Freemantle C, Thomas E, et al: Comparison of measurement sof body composition by total body potassium, bioimpedance analysis, and dual-energy x-ray absorptiometry in hypopituitary adults before and during growth hormone treatment. Am J Clin Nutr 61:1186-1194, 1995
124
DUMLER AND KILATES
57. de Boer H, Blok GJ, Voerman B, et al: The optimal growth hormone replacement dose in adults, derived from bioimpedance analysis. J Clin Endocrinol Metab 80:2069-2076, 1995 58. Briganti M, Emiliani G, Montanari A, et al: Longitudinal assessment of body composition in CAPD patients using bioelectric impedance analysis. A comparison with hemodialysis patients. ASAIO J 41:M725-M727, 1995 59. Johannsson G, Bengtsson B-A, Ahlme´n J: Double-blind, placebo-controlled study of growth hormone treatment in elderly patients undergoing chronic hemodialysis: Anabolic effect and functional improvement. Am J Kidney Dis 33:709-717, 1999 60. Bergia R, Bellini ME, Valenti M, et al: Longitudinal assessment of body composition in continuous ambulatory peritoneal dialysis patients using bioelectric impedance and anthropometric measurements. Perit Dial Int 13:S512-S514, 1993 (suppl 2) 61. Chertow GM, Laqarux JM, Lew NL, et al: Development
of a population-specific regression equation to estimate total body water in hemodialysis patients. Kidney Int 51:1578-1582, 1997 62. Lukaski H: Validation of body composition assessment techniques in the dialysis population. ASAIO J 43:251-255, 1997 63. Fisch BJ, Spiegel DM: Assessment of excess fluid distribution in chronic hemodialysis patients using bioimpedance spectroscopy. Kidney Int 49:1105-1109, 1996 64. Ott M, Fischer H, Polat H, et al: Bioelectrical impedance analysis as a predictor of survival in patients with human immunodeficiency virus infection. J Acquir Immune Defic Syndr 9:20-25, 1995 65. Maggiore Q, Nigrelli S, Ciccarelli C, et al: Nutritional and prognostic correlates of bioimpedance indexes in hemodialysis patients. Kidney Int 50:2103-2108, 1996 66. Chertow GM, Jacobs DO, Lazarus JM, et al: Phase angle predicts survival in hemodialysis patients. J Ren Nutr 7:204-207, 1997