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  1. XV CONVEGNO NAZIONALE GRUPPO DI STUDIO DIALISI PERITONEALE BARI 18-20 MARZO 2010 LA BIOIMPEDENZA E’ UN UTILE STRUMENTO CLINICO ? Paolo Lentini Struttura Complessa di Nefrologia e Dialisi Ospedale San Bassiano Bassano Del Grappa

  2. From PD gudelines (ISPD) • Biocompatible PD solutions - normal pH, low concentration of glucose • Insertion of PD catheter – 10 days-6 weeks before RRT • urea / creatinine clearance measured every 6 months • PET: 6 weeks after commencing treatment + annually • Avoid routine use of high glucose concentrations )use of icodextrin, aminoacids instead) • Preserve residual diuresis, obtain UF above 750 ml/day [hydration status] • Peritonitis and exit-site infection rates, regular revision of technique • Invasive procedures cover by ATB prophylaxis • Topical ATB administration if needed (S.aureus, Ps. aeruginosa) • Beware central obesity and malnutrition ISPD GUIDELINES/RECOMMENDATIONS Perit Dial Int 2006; 26:520–522

  3. I. CLINICAL PRACTICE GUIDELINES FOR PERITONEAL DIALYSIS ADEQUACY GUIDELINE 3: PRESERVATION OF RESIDUAL KIDNEY FUNCTIONProspective randomized trials of dialysis adequacy and many observational studies have confirmed a strong association between the presence of RKF and reduction of mortality in patients on PD therapy. It is important to monitor and preserve RKF. (A) GUIDELINE 4. MAINTENANCE OF EUVOLEMIA Volume overload is associated with CHF, left ventricular hypertrophy (LVH), and hypertension; therefore, it is important to monitor ultrafiltration volume, dry weight, sodium intake, and other clinical assessments of volume status.

  4. CLINICAL PRACTICE GUIDELINES FOR PERITONEAL DIALYSIS NUTRITION Guideline B. • Assessment of nutritional status For PD patients should be routinely assessed using a panel of measures. • The frequency of using these measures has not been verified, but a 6 monthly review is desirable. • Serum albumin, prealbumin, creatinine and creatinine index, dietary interviews and diaries, protein equivalent of nitrogen appearance (nPNA), subjective global Assessment (SGA), anthropometry and dual-energy X- ray photon absorptiometry (DEXA) are all measures utilized to assess nutritional status and their evidence for use will be substantiated. EBPG Nutrition Nephrol Dial Transplant (2005) 20 [Suppl 9]

  5. Methods for Body Composition Assessment • Diluition Techniques – Reference method • 2H, 3H, 18O, NaBr; • Dual Energy X-ray Absorptiometry (DEXA)- Reference method • Computed Tomography and Magnetic Resonance Imaging • Site Specific images - IAAT • Densitometry – • Hydrostatic Weighing, BodPod • Electrical Impedance Techniques • BIA (single & multi- frequency) • BIS – Cole-Cole Model • Skinfolds & Anthropometric • Body Mass or Weight

  6. References Methods • Dilution Techniques • Deuterium (2H) exchanges with H2O – reference method for Total Body Water • NaBr (sodium-bromide) dilution doesn’t cross cell membrane – ECF space • Requires pre- and post- dilution specimen (serum, urine) and mass spectrometer • Dual Energy X-ray Absortiometry (DXA) • X-ray • Measures Bone Mineral Content (BMC) • Bone Free Soft Tissue (BFST) • BMC + BFST = FFM • Distribution of Fat and Lean Tissue

  7. PRINCIPLES OF BIA The resistance (R) of an of homogeneous material of uniform cross-sectional area is proportional to its length (L) and inversely proportional to its cross sectional area (A). The body offers two types of R to an electrical current: capacitative R (Reactance), and resistive R (simply called Resistance). Reactance (Re or X): Capacitative R CELL MEMBRANES Reactance (R): Extra and Intracellular FLUIDS Impedance (Z): Relation between X and R Phase Angle (PA): Lower phase angles: decreased cell integrity A basic assumption of BIA is that the sum of the arm, trunk and leg volumes can be modeled as a cylinder with uniform conductivity.

  8. CLASSIFICATION • BIA: Bioelectrical Impedance Analysis • SF-BIA: Single Frequency Bioelectrical Impedance Analysis • MF-BIA: Multi Frequency Bioelectrical Impedance Analysis • BIS: Bioelectrical Impedance Spectroscopy • BIVA: Bioelectrical Impedance Vector Analysis • W-BIA: Whole Body Bioelectrical Impedance Analysis • S-BIA: Segmental Bioelectrical Impedance analysis

  9. CLINICAL USE OF BIA IN PD • BODY COMPOSITION ASSESSMENT • MANAGEMENT OF EXTRACELLULAR FLUID (DRY WEIGHT) • ASSESSMENT OF NUTRITIONAL STATUS Nearly 2000 papers about BIA are found in English medical literature 1990-2010, 1200 being pubblished in the last 7 years.

  10. MACHINES FOR BIOIMPEDANCE ANALYSIS • Quantum II (RLJ System) • SC-331 S (Tanita Corporation) • ElectroFluidGraph (Akern s.r.l.) • SFB7 (Impedimed Ltd.) • Bioscan 916S (Maltron Ltd. • Body Composition Monitor (Fresenius Medical Care)


  12. BODY COMPARTMENTS • TBW:Total Body Water • ECW:Extracellular Water • ICW:Intracellular Water • BF:Body Fat • FFM:Fat-free Mass • FM:Fat Mass


  14. Dry weight “The lowest [post-dialysis] weight a patient can tolerate without intradialytic symptoms and/or hypotension and in the absence of overt fluid overload”Henderson KI 17: 571-576; 1980 “ The post-dialysis weight at which the patient is and remains normotensive until the next dialysis in spite of interdialytic fluid retention and without antihypertensive medication”Charra 1996

  15. CONCEPT OF DRY WEIGHT EXCESS FLUID WEIGHT • Clinical assessment of dry weight is a difficult task in PD patients by the lack of treatment associated signs indicative of dehydration as may be observed in HD patients such as intradialytic hypotension or cramps. • Useful monitoring tools for fluid status estimation during HD like as on line blood volume and blood pressure measurement are not availble for application in PD patients DRY WEIGHT

  16. Physical examination should always be the basis for assessment dry weight in dialysis patients. However, as sometimes physical examination allows no definite conclusion , several non-invasive methods have been developed.

  17. VOLUME • Body Weight • Blood Pressure • Edema • Diuresis • Skin and Mucous hydration • Hematocrit • Electrolites Disorders • Chest X-Ray

  18. NO INVASIVE U.S. Inferior vena caval diameter Bio Impedance Analysis (BIA) Natriuretic Peptides (ANP, BNP,CNP) INVASIVE Central Venous Pressure (CVP) Pulmunary Artery Occlusion Pressure (PAOP) Cardiac Output ( SVV, SVO2) VOLUME EVALUATION

  19. INFERIOR VENA CAVAL DIAMETER Overhydration: VCD > 11, CI < 40% Ideally measured 2hrs post dialysis Limitations: Operator variability, heart failure Timing of measurements is of pivotal importance for VCD, reference value of 8mm/m2 obtained 2 h after dialysis.

  20. Natriuretic peptides and the dialysis patient BNP correlates well with cardiac function, and is a good prognosticator for risk stratification ANP is sensitive to volume changes during dialysis, but changes in concentration do not predict achievement of euvolemia. Suresh et al. Seminars in Dialysis 2005

  21. SF-BIA SF-BIA, injecting 800 µA and 50 kHz alternating sinusoidal current is passed between surface electrodes placed on hand and foot. At 50 kHz, the current passes through both intra and extracellular fluid; LIMITS • SF-BIA permits to estimate TBW from equations derived from healthy subjects; • Fat-free mass is estimated by assuming TBW content is 73%, and fat is derived as weight minus FFM. Thus, both of these are potentially unreliable in situations with abnormal FFM hydration. • Accuracy is not enough for clinical use due to the individual variation in Body composition

  22. MF-BIA and BIS • Frequencies vary from 5 kHz – 1MHz • In biological tissues lower frequency currents travel preferentially in the extracellular space,whereas high frequency currents traverse both ECV and ICV. • Use of prediction equations - not independent of TBW • Cole-Cole model is applying to calculate extracellular and intracellular resistance

  23. At low frequency (below 30 kHz) the current travels through the ECF At high frequency the current travels through both the ECF and ICF MF-BIA AND BIS

  24. Ri (Impedance Intracellular) Determined mathematically by parallel subtraction of Rinf and R0 BIS R0 Rinf Scans from low (4 kHz) to high (1000 kHz) frequencies 400-500 discrete data points Impedance at 0 kHz (Impedance ECF) Impedance at infinite KHz (Impedance TBW) Bioimpedance Spectroscopy (BIS)

  25. Key Points Ri (ohm) ICF (Litres) Height of the patient must be known to calculate volumes from the raw data (R0 and Ri). If calculating Fat Mass in addition to fluid volumes the body weight of the patient must be known. Transformation Transformation Impedance intracellular 14.2 L (Hanni mixture theory) (Hanni mixture theory) TBW (Litres) 36.4 L (14.2 + 22.2) R0 (ohm) ECF (Litres) Impedance extracellular 22.2 L Transformation

  26. Assumption 1 Assumption 2 Assumption 3 Body is made up of 5 cylinders (2 arms, 2 legs and the chest/abdomen) These are filled with fluid and suspended cells of a homogenous type and density The cylinders have a homogenous conductive properties (resistivities) Assumptions of the Hanni Mixture theory

  27. To assess abnormalities in body composition in 40 PD patients and in fluid status between • MF-BIA • Segmental BIA • Watson formula • Diluition methods (deuterium oxide [D02] for TBW and Bromide Diluition [NaBr]for ECW and DEXA for for body composition)

  28. RESULTS MF-BIA tended to underestimate TBW according to D2O Whereas the Watson formula tended to overstimate TBW according to D2O

  29. TBW: (D20 vs MF-BIA) 2.0 ± 3.9 L • ECW: (NaBr vs MF-BIA) -2.8 ± 3.9 L BIA techniques did not appear to have significant advantages over the Watson formula to predicting TBW

  30. MF-BIA AND BIS Limits • MF-BIA was unable to detect changes in the distribution of fluid between extracellular and intracellular spaces in OVERHYDRATED patients; • BIS: Modeling for body cell mass derived from spherical model (Cole-Cole Plot); muscle mass are non-spherical, but rather cylindrical. This difference in geometry may account for the understimation of R; • Standard error by BIS for ECV measurement in healthy subjects is> ±1 Land that of ICV is > ±1.5 Llimiting their clinical utility to dry weight determination;

  31. BIVA The BIVA approach developed by Piccoli permits patient evaluation from the direct measurement of the impedance vector and does not depend on equations or models. In BIVA, R and reactance (Xc), standardized for height, are plotted as point vectors in the R-Xc plane. An individual vector can then be compared with the reference 50%, 75%, and 95% tolerance ellipses calculated in the healthy population of the same gender and race (R Xc graph method)

  32. Cross-Sectional Study: 200 CAPD adults patients (149 without edema and 51 with edema). SF-BIA Rxc Graph (BIVA) was performed and measured TBW compared with: • 726 Healthy subjects • 1116 Hemodialysis patients • 50 Nephrotic patients

  33. The mean impedance vector of CAPD patients without edema was half way between the mean vectors of the healthy population and the HD population before the hemodialysis session.

  34. BIVA: Limits An individual vector can be compared with the reference 50%, 75%, and 95% tolerance ellipses calculated in the healthy population of the same gender and race

  35. SEG-BIA Segmental-BIA is performed by either placing two additional electrode on wrist and foot on the opposite side, or by placing sensor electrodes on wrist, shoulder (acromion), upper iliac spine and ankle. The trunk of the body contributes only as 10% to whole bodyimpedance; This implies three aspects : • Changes of the impedance are closely related to changes of the FFM (or muscle mass or body cell mass (BCM)) of the limbs; (2) Changes of the FFM of the trunk are probably not adequately described by whole body impedance measurements; (3) Segmental BIA must be used to determine fluid shifts and fluid distribution in some diseases (ascites, renal failure, surgery), and may be helpful in providing information on fluid accumulation in the pulmonary or abdominal region of the trunk (PD?) Composition of the ESPEN Working Group; Clinical Nutrition (2004) 23, 1226–1243

  36. AIM:Using Segmental BIA to determine the characteristics of fluid shift of each body segment in 13 CAPD patients before and after PD solution exchange Method:Seg-BIA Trunk, arms and legs 1 h before and 1 and 2 hors later PD solution exchange

  37. IMPEDANCE (ω) ARMS: Increased 1 h after drainage; LEGS:Decrease after exchange; TRUNK: Increase 1 h after drainage; TBW (L) ARMS: - 0.25 L LEGS: + 0.47 L TRUNK: -0. 25 L RESULTS TRUNK ARMs LEGs The change in body weight significantly correlated with total net calculated water volume change (p = 0.009)

  38. 14 CAPD patients during standard exchange with fluids of known conductivity. Bioimpedance was continuously measured in the arm, trunk, and leg and from wrist to ankle. Volume changes were calculated using both segmental BIA (SBIA) and wrist-to-ankle BIA (WBIA) and were compared with volume changes measured gravimetrically.

  39. When 2.19 ± 0.48 L were removed from the peritoneal cavity during draining, 95.2 ± 3.8% of this volume was detected by SBIA compared with 12.5 ± 24.3% detected by WBIA. When 2.11 ± 0.20 L of fresh dialysate was infused into the peritoneal cavity, 91.1 ± 19.6% of this volume was detected by SFBIA compared with only 8.86 ± 21.1% detected by WBIA.

  40. SEGMENTAL BIA LIMITS • Segmental-BIA requires prior standardization, particularly when different approaches and different BIA devices are employed; • Standardization of the type of electrodes used and their placement; • In literature we found very high relative errors with segmental-BIA for arms and legs FFM: 13–17% for arm FFM and 10–13% for leg FFM.


  42. NUTRITIONAL STATUS • MF-BIA: Body cell mass are derived from from DEXA in healthy as well as TBW are derived from D2O diluition in healthy:in conditions of abnormal fluid distribution can affect resistance and the error must be significant for FFM • SF-BIA and FFM: BIA measure primarly TBW when the high correlations with FFM assume that the hydration costant is stable at 73%. In overhydrated patient the use of SF-BIA or MF-BIA or BIS to estimate FFM for nutritional assessment may lead to erroneous results

  43. PHASE ANGLE PhA has been correlated with the disease prognosis in HIV- Infection, hemodialysis, peritoneal dialysis, chronic renal failure and Liver cirrhosis patients: these study suggest that PhA may be useful in determining increased risk of morbidity and that PhA decreased with age

  44. This study prospectively examined the relationship of bioimpedance indexes to the nutrition status and survival of 45 PD patients who were followed for more than 1°year.

  45. The cumulative observed survival of PD patients with an enrollment phase angle >6 degrees was significantly (p= 0.01) Higher than that of patients with an Enrollment phase angle <6 degrees. The BIA indices reflect nutrition status in PD patients, and may be useful in Monitoring Nutrition Fein PA, Advances in Peritoneal Dialysis, Vol. 18, 2002

  46. OTHERS APPLICATIONS OF BIA TO PD • Outflow Failure • Dialysis Adequacy (Mendley et al ):Kt/V urea in pediatric PD patients utilizing TBW for volume (by SF-BIA) and compared with deuterium diluition.(mean difference 0.33± 1.44 L ns) • Blood Pressure Control and fluid status in PD (Wang et al):ECV higher in uncontrolled hypertension

  47. SEGMENTAL BIA IN PD • Outflow failure, defined by the incomplete recovery of instilled fluid, is observed frequently in PD patients. Kinking of the catheter, malpositioning, omental occlusion and constipation are commonly observed, but it is important to exclude dialysate leakage as the underlying cause. The initial manifestations of dialysate leakage may be subtle. • Intra-abdominal fluid volume determined by segmental BIA could aid differential diagnosis of outflow failure (catheter problem versus leakage) and reduce the need for imaging studies.

  48. BIA UNSOLVED PROBLEMS • Limitations of BIA equations • Limitations of Reference Methods • Limitations with reference study population (Ethins specificity differences) • Limitations imposed by uremia and dialytic process on BIA measurement • Common errors in BIA application

  49. LIMITATIONS OF BIA EQUATIONS (1) • Regression Functions (for SF-BIA): Based on experimental data derived from healthy population; • Model that used equations based on the knowledge of extra- and intracellular volume space distribution (for MF-BIA and BIS) for bicompartimental model; • The trunk contributes only a small proportion to whole body impedance;