BCM: un nuovo approccio alla personalizzazione del

trattamento

Dott. Gianpaolo Amici

U.O. Nefrologia e Dialisi

Ospedale di Treviso

USRDS 2009 Adjusted mortality rates

USRDS 2009 Change in hospitalization rates

USRDS 2004 Risk of death (cause and modality)

Vi sono evidenze sempre maggiori dei legami tra mortalità, IVS, idratazione e pressione arteriosa in dialisi

Original investigation

J NEPHROL 2002; 15: 655-660

Impact of volume control on left ventricular hypertrophy in dialysis

patients

Mehmet Özkahya1, et al, Ege University Medical Faculty, Bornova, Izmir

- Turkey

La pressione arteriosa da sola non è un buon indice di idratazione visti i rapporti indiretti tra idratazione e pressione arteriosa

Resistenze Vascolari

Periferiche

Pressione Arteriosa

Gettata Cardiaca

Volemia

La valutazione clinica dell‗idratazione

Idratazione

Quantità di

farmaci

ipotensivi

Esami

strumentali

Segni e

sintomi

Pressione

arteriosa

Ipervolemia, ipertensione e patologia cardiovascolare in DP

Lameire N, et al. Cardiovascular diseases in peritoneal dialysis patients: the size of the problem. Kidney Int Suppl. 1996 Nov;56:S28-36.

Lameire N, Van Biesen W. Importance of blood pressure and volume control in peritoneal dialysis patients. Perit Dial Int. 2001 Mar-Apr;21(2):206-11.

Khandelwal M, et al. Volume expansion and sodium balance in peritoneal dialysis patients. Part I: Recent concepts in pathogenesis. Adv Perit Dial. 2003;19:36-43.

Khandelwal M, et al. Volume expansion and sodium balance in peritoneal dialysis patients. Part II: Newer insights in management. Adv Perit Dial. 2003;19:44-52.

Wang AY. Cardiovascular risk factors in peritoneal dialysis patients revisited. Perit Dial Int. 2007 Jun;27 Suppl 2:S223-7.

Wang AY. The John F. Maher Award Recipient Lecture 2006. The "heart" of peritoneal dialysis:residual renal function. Perit Dial Int. 2007 Mar-Apr;27(2):116-24.

Van Biesen W, et al. Residual renal function and volume status in peritoneal dialysis patients: a conflict of interest? J Nephrol. 2008 May-Jun;21(3):299-304.

Brunkhorst R. Hypervolemia, arterial hypertension and cardiovascular disease: a largely neglected problem in peritoneal dialysis. Clin Nephrol. 2008; Apr;69(4):233-8.

Carvalho MJ, Rodrigues A. Importance of residual renal function and peritoneal dialysis in anuric patients. Contrib Nephrol. 2009;163:155-60.

Piraino B. Cardiovascular complications in peritoneal dialysis patients. Contrib Nephrol. 2009;163:102-9.

Wang MC, et al.BLOOD PRESSURE AND LEFT VENTRICULAR HYPERTROPHY IN PATIENTS ON DIFFERENT PERITONEAL DIALYSIS REGIMENSPerit Dial Int 2001; 21: 36–42

―In this study, ambulatory nighttime systolic BP load >30% had an independent association with LVH. Office and home BP measurements were correlated with ABPM in PD patients. The result that CCPD patients had a higher LVMI than CAPD patients may be due to a relative volume overload during the daytime in CCPD patients‖.

Correlazione tra IVS, PA e regimi dialitici:

>tempo PA elevata = > IVS

> UF = > IVS

i(t)

~

measurement

U(t)

Apply AC

BCM-Body Composition MonitorPrincipio di base delle frequenze multiple

Zero frequency

(Cell behaves as an

insulator)

Cell

Medium frequency

(50 kHz)

(Cell behaves as a

partial insulator)

High frequency

(Cell behaves as an

ordinary conductor)

Cell

Cell

ECW

ECW

ECW

Range di misurazione: la curva dell‗impedenza

Physiologic

impedance curve

of patient

Information about body

composition

Solo con Bioimpedance spectroscopy (BIS) è possibile

valutare la curva fisiologica dell‘impedenza.

BIA BIS

Meas. range BIS

Rinf

b a cute/ossag = cute

R0

5kHz1MHz

BIA(50 kHz)

Resistance

Reaktance

Come sono le curve di impedenza nei pazienti?

Resistance [Ohm]

200 300 400 500 600 700 800 900

Re

ak

tan

ce

[O

hm

]

0

10

20

30

40

50

60healthy subject

malnourished patient

fluid overloaded

patient

The impedance curves of patients are very different from healthy subjects.

To assess the body composition in healthies the complete curve must be measured.

Resistance

Reactance

Impedenza multifrequenza e composizione corporea

5kHz1MHz

Fluid Model • ECW, ICW

Body Model• Lean tissue

• Fat

• excess Fluid

Weight, Height

R R0

Excess

fluid

Lean

tissue

Adipose

tissue

Proteins

& minerals

Lipids &

minerals

≈ 100%

water

20 %

water

70%

water

Il modello a 3 compartimentiBase del modello di composizione corporea del BCM ….

Moissl UM, et al. Physiol Meas 2006; 27: 921-933.

Chamney PW, et al. Am J Clin Nutr 2007; 85: 80-9.

Ottima concordanza tra BCM e metodi di riferimento

R²=0,91p<0,001

TBW: -0.2 ± 2.3 L

BIS Xitron Hydra 4200

152 soggetti normali

Deuterio-trizio

bromuro di sodio-potassio

Validazione dell‘analisi composizione corporea(massa grassa con DEXA)

0

10

20

30

40

50

60

70

80

0 10 20 30 40 50 60 70 80

Fat BCM [kg]

Fat D

XA

[kg]

Younger Healthies (Age < 50)

Older Healthies (Age > 50)

Dialysis patients

BCM – aspetto delle schermate

… measures

non-invasively, fast and easy

… quantifies

individual overhydration (L)

… provides

a basis for nutritional

assessment

… determines

urea distribution volume (L)

Grafico analisi di un singolo paziente nel tempo con software BCM

Body Composition measured with BCM

10.4.06 17.4.06 24.4.06 1.5.06 8.5.06 15.5.06 22.5.06 29.5.06

weig

ht

[kg

]

10

20

30

40

50

60

70

LTM BCM

Fat BCM

Overhydration BCM

Combining Blood Pressure and Fluid Overload

Fluid Overload

BP

[m

mH

g]

Normovolemia

Normotension

140

1.1 L

- heart disease

- medication

-1.1 L

• hypertension

• hypervolemia

• normotension

• Hypervolemia(problemi di pompa?)

• hypertension

• Normovolemia(sclerosi?)

• normotension

• normovolemia

PA e idratazione con BCM in dialisi

Towards improved cardiovascular management: la necessità di

correlare la PA e l’OH

P. Wabel, et al. NDT, 2008. 500 prevalent HD patients from 8 European

centers (Germany, Poland, UK, Portugal, Cz)

BCM e HD-HDF

Le patient cards del BCM (nuovo sw 3,2 ) possono essere lette dalle 5008 che hanno installato l'ultimo sw 4,00 . I dati che esse possono trasferire sono: nome, cognome e volume di distribuzione dell'urea necessario al 5008 per calcolare il KT/V. La 5008 invece trasferisce nelle patient cards la pressione sistolica e diastolica che servono per sviluppare il grafico "Hydration Ref." del Fluid Management Tool.

Letteratura attuale sul BCM

Moissl UM, et al. Body fluid volume determination via body composition spectroscopy in health and disease. Physiol Meas. 2006 Sep;27(9):921-33.

Chamney PW, et al. A whole-body model to distinguish excess fluid from the hydration of major body tissues. Am J Clin Nutr. 2007 Jan;85(1):80-9.

Wizemann V, et al. Whole-body spectroscopy (BCM) in the assessment of normovolemia in hemodialysis patients. Contrib Nephrol. 2008;161:115-8.

Wabel P, et al. Towards improved cardiovascular management: the necessity of combining blood pressure and fluid overload. Nephrol Dial Transplant. 2008 Sep;23(9):2965-71.

Wizemann V, et al. The mortality risk of overhydration in haemodialysis patients. Nephrol Dial Transplant. 2009 May;24(5):1574-9.

Wabel P, et al. Importance of whole-body bioimpedance spectroscopy for the management of fluid balance. Blood Purif. 2009;27(1):75-80.

Crepaldi C, et al. Application of body composition monitoring to peritoneal dialysis patients. Contrib Nephrol. 2009;163:1-6.

Machek P, et al. Guided optimization of fluid status in haemodialysis patients. Nephrol Dial Transplant. 2010 Feb;25(2):538-44.

Devolder I, et al. Body composition hydration and related parameters in hemodialysis versus peritoneal dialysis patients. Perit Dial Int 2010; 30: 208—14.

ObjectiveApart from adequate management of the fluid status in peritoneal dialysis (PD) patients thenutritional aspect of the therapy is equally important for the patient‘s morbidity andmortality. In this cross-sectional study body composition data was obtained with the BodyComposition Monitor (BCM, Fresenius Medical Care) to identify relevant variables foroptimized nutritional outcomes.

MethodsWe screened 973 PD patients from 28 centers in 6 European countries. 639 patients met theinclusion/exclusion criteria. Body composition, blood pressure (BP), dialysis modality andprescription, pre-existing diseases, comorbidities, and antihypertensive medication weredocumented and analyzed.

ResultsMean body mass index (26.3±5.1 kg/mq) and fat tissue index (12.6±6.0 kg/mq) were slightlyabove the normal range whereas mean lean tissue index (13.4±3.4 kg/mq, LTI) was withinnormal range at a mean weight of 72.2±15.4kg and height of 166±9.6 cm. Patients on

glucose PD solutions alone had a statistically significantly better outcome than those onpolyglucose or amino acid solutions in regard of nutritional parameters like lean tissue index.

ConclusionsThe study provides essential information on nutritional status in a large representative cohortof European PD patients. BCM measurement enables clinicians to obtain objective data onpatient‘s body composition regarding fat tissue, lean tissue, and fluid status in routine clinicalpractice to optimize PD therapy and patient outcomes.

Nutritional Assessment Using Body Composition Monitoring inPeritoneal Dialysis Patients. Variables Determining Body Mass,

Fat Tissue and Lean Tissue Index. Covic A (Van Biesen W), et al.

Devolder I, et al.BODY COMPOSITION, HYDRATION, AND RELATED PARAMETERS IN HEMODIALYSIS VERSUS PERITONEAL DIALYSIS PATIENTS.Perit Dial Int 2010; 30: 208–214

―Confrontando pts HD vs PD non si sono mostrate particolari differenze sia per la PA che per l‘OH. Questo dimostra come non sia vero che i pts in PD siano maggiormente idratati‖.

The Hydration Status in a Hemodialysis (HD) Population: Comparison between the Medical Assessment and Evaluation

by Multifrequency Bioimpedance Spectroscopy (BIS)Malheiro J, Mancini E, Mambelli E, Facchini MG, Lopez A, Persico A, Santoro A.

Poster ASN 2009

BIS measurements for OH evaluation were performed on our HD patients before a HD session. A total of 104 measurements were evaluated, representing 90 patients (55 M, 35 F; age 57.9yrs; height 167.3cm; weight 70.6 kg). BCM data: lean tissue mass (LTM), adipose tissue mass (ATM) and OH. Clinical data: DW, height, age and sex. The OH value was recorded by clinical evaluation (cOH) and as a result of the BIS evaluation (bOH). The difference between the cOH and bOH was represented by dOH and its absolute value by |dOH|. Possible predictors were tested by non-parametric Mann Whitney U test or the Fisher exact probability test. Fifty percent of the determinations of dOH were lower than 1.0Kg and 75% were <2.0 Kg.

The Hydration Status in a Hemodialysis (HD) Population: Comparison between the Medical Assessment and Evaluation by

Multifrequency Bioimpedance Spectroscopy (BIS)Malheiro J, Mancini E, Mambelli E, Facchini MG, Lopez A, Persico A, Santoro A.

Poster ASN 2009

Figure 1 shows that the bOH value is higher than cOH in a severely overhydrated patient. No significant correlations resulted from the linear regression between LTM or ATM and dOH. Height and age resulted as predictors of |dOH| when two subgroups were defined, using its 3rd

quartile value as threshold (77 measurements<2 and 27 2). A good correlation between clinical and BIS-based OH determination was found. The bOH was more accurate in patients with severe overhydration. This device could prove particularly useful in severely overhydrated patients, in whom a correct DW target is more difficult to set and reach in adequate time.

We studied 70 pts, all were in good nutritional conditions, in self-HD units (age 58 15 years, BMI 25 5 kg/m2, albumin 37 5 g/L, prealbumin 0.35 0.8 g / L, CRP 8 0.1 g/L, spKt/V 1.5 0.3, nPCR 1.15 0.30 g/kg /d). The measure was done before HD session to ensure stability of the body fluid compartements. The patient was weighed and measured by the same examiner. The lean mass and body fat (lean tissue index: LTI, fat tissue index: FTI) are normalized by square body height and compared with a reference range derived from1000 healthy controls, according to gender and age.59% of women and 29% of men have values of LTI below the 10th percentile. 34% of females and 37% of males exhibits a FTI higher than 90th percentile. The standard nutritional markers (BMI, albumin, prealbumin, creatinin, nPCR) are not able to detect sarcopenia, a well-known risk factor for mortality since no difference exists between the 2 populations (LTI low or within the reference range). 50% of patients associated high fat mass but low LTI.

In conclusion, the BCM is a simple tool that helps to detect sarcopenia in patients undergoing dialysis. The repeated measures helps to guide the association nutritional support - physical rehabilitation.(aiuto nella valutazione dei pazienti con perdita di massa magra)

Chauveau P, et al. Assessment of Body Composition and Sarcopenia in Hemodialysis Patients Using the

Body Composition Monitor (Poster ASN 2009)

Amici G, et al. Analisi Della Composizione Corporea Con Spettroscopia BCM E BioimpedenzaCon Analisi Vettoriale In Dialisi Peritoneale. (Poster Bari XV° Congresso Nazionale di Dialisi Peritoneale).

Misurazioni con spettroscopia BCM e BIVA , 40 pazienti prevalenti , 60±17 anni, in DP da 22 mesi (2-137), peso 70±12 kg , BMI di 25.1±3.8 kg/mq, la PAS era 152±30 e la PAD era 92±13 mmHg, la CLCR settimanale totale/1.73 mq era 65±20 L, il Kt/V settimanale totale era 2.25±0.47, il GFR mediano 2.04 ml/min (0-7.5), la diuresi residua mediana 640 ml (0-2050). Il 90% dei pazienti era in trattamento antipertensivo con una mediana di 2 farmaci (1-4) e una WHO-ATC/DDD mediana di 3.0 (0.1-8.3). La misurazione di resistenza e angolo di fase a 50 kHz con i due apparecchi ha mostrato una buona correlazione lineare (r=0.992 e r=0.887, rispettivamente). Dalle misurazioni BCM l’iperidratazione (OH) era 1.2 L (da -2.1 a +5.8) con 51% iperidratati, 41% normali e 8% disidratati, mentre alla valutazione qualitativa BIVA 44% erano iperidratati, 46% normali e 10% disidratati, con una discreta corrispondenza tra le due classificazioni (Chisq. p<0.01, Kappa 0.38). E’ stata infine verificata una buona correlazione tra massa magra misurata da BCM (LTI, 133 kg/mq) e l’angolo di fase della BIVA (r=0.666 p<0.001)

Amici G, et al. Analisi Della Composizione Corporea Con Spettroscopia BCM E Monitoraggio Clinico In Dialisi Peritoneale. (Poster Bari 2010 XV° Congresso Nazionale di Dialisi Peritoneale).

Oltre ai dati precedenti con ecocardiografia il LVMI Devereux-Penn era 164±50 g/mq, Relative Wall Thickness del VS era 0.51±0.11 e la FE% 67.1±7.8. Dalle misurazioni BCM TBW era 35±7 L, ECW 17±3 L, ICW 18±4 L, l’iperidratazione (OH) stimata mediana era 1.2 L (-2.1-+5.8), la massa magra 37±10 kg (53±13%), la massa grassa 23±8 kg (33±9%). E’ stata osservata una correlazione inversa tra OH e diuresi residua (r=-0.322, p<0.05), OH e GFR (r=-0.418, p=0.01), OH e FE% (r=-0.337, p<0.05), mentre è stata osservata una correlazione diretta tra OH e LVMI (r=0.347, p<0.05). Il BMI e la percentuale di massa grassa sono risultate correlate con l’età dialitica (r=0.357 p<0.05, r=0.449 p<0.01, rispettivamente).

Grafici delle misurazioni nel gruppo di 40 pazienti in dialisi peritoneale di TV

Resistance [Ohm]

200 300 400 500 600 700 800 900

Re

ak

tan

ce

[O

hm

]

0

10

20

30

40

50

60

healthy

malnourished

fluid overloaded

Ogni paziente è rappresentato da una curva di diverso colore

BCM e BIA – Angolo di fase

2

3

4

5

6

7

8

9

Ph

ase A

3 4 5 6 7

Phi 50 kHz [°]

Bivariate Normal Ellipse P=0,950

Phi 50 kHz [°]

Phase A

Variable

5,110769

5,284615

Mean

1,040727

1,089311

Std Dev

0,887227

Correlation

0,0000

Signif. Prob

39

Number

Correlation

Biv ariate Fit of Phase A By Phi 50 kHz [°]

-2,0

-1,5

-1,0

-0,5

0,0

0,5

1,0

1,5

2,0

Diff

ere

nce

: Ph

i 50

kH

z [°

]-P

ha

se A

Phase A

Phi 50 kHz [°]

3 4 5 6 7 8

Mean: (Phase A+Phi 50 kHz [°])/2

Phi 50 kHz [°]

Phase A

Mean Difference

Std Error

Upper95%

Lower95%

N

Correlation

5,11077

5,28462

-0,1738

0,08134

-0,0092

-0,3385

39

0,88723

t-Ratio

DF

Prob > | t|

Prob > t

Prob < t

-2,13718

38

0,0391

0,9805

0,0195

Difference: Phi 50 kHz [°]-Phase A

Matched Pairs

BCM e BIA - Resistenza

300

350

400

450

500

550

600

650

700

750

R B

IA

300 350 400 450 500 550 600 650 700 750

Z 50 kHz [Ohm]

Bivariate Normal Ellipse P=0,950

Z 50 kHz [Ohm]

R BIA

Variable

512,0513

504,4359

Mean

81,50739

79,51028

Std Dev

0,991845

Correlation

0,0000

Signif. Prob

39

Number

Correlation

Biv ariate Fit of R BIA By Z 50 kHz [Ohm]

-50

-40

-30

-20

-10

0

10

20

30

40

50

Diffe

ren

ce

: Z

50 k

Hz [O

hm

]-R

BIA

R BIA

Z 50 kHz [Ohm]

300 350 400 450 500 550 600 650 700 750

Mean: (R BIA+Z 50 kHz [Ohm])/2

Z 50 kHz [Ohm]

R BIA

Mean Difference

Std Error

Upper95%

Lower95%

N

Correlation

512,051

504,436

7,61538

1,67703

11,0103

4,22044

39

0,99185

t-Ratio

DF

Prob > | t|

Prob > t

Prob < t

4,541

38

<.0001

<.0001

1,0000

Difference: Z 50 kHz [Ohm]-R BIA

Matched Pairs

Massa magra con BCM e angolo di fase BIA

2

3

4

5

6

7

8

9

Ph

ase A

6 8 10 12 14 16 18 20

LTI [kg/m²]

Bivariate Normal Ellipse P=0,950

LTI [kg/m²]

Phase A

Variable

13,23243

5,275676

Mean

2,910332

1,100355

Std Dev

0,665987

Correlation

0,0000

Signif. Prob

37

Number

Correlation

Biv ariate Fit of Phase A By LTI [kg/m²]

Iperidratazione e dati ecocardiograficiIndici indiretti per valutare se il BCM offre un supporto clinico

40

45

50

55

60

65

70

75

80

85

EC

C F

E%

-3 -2 -1 0 1 2 3 4 5 6

OH [L]

Bivariate Normal Ellipse P=0,950

OH [L]

ECC FE%

Variable

1,331429

67,07714

Mean

1,923198

8,726501

Std Dev

-0,33729

Correlation

0,0475

Signif. Prob

35

Number

Correlation

Biv ariate Fit of ECC FE% By OH [L]

100

150

200

250

LV

MI D

eve

reux-P

en

n g

/mq

-3 -2 -1 0 1 2 3 4 5 6

OH [L]

Bivariate Normal Ellipse P=0,950

OH [L]

LVMI Devereux-Penn g/mq

Variable

1,331429

164,0497

Mean

1,923198

50,15456

Std Dev

0,346941

Correlation

0,0412

Signif. Prob

35

Number

Correlation

Biv ariate Fit of LVMI Devereux-Penn g/mq By OH [L]

Valutazione bcm e frazione di eiezione misurata con ecocardio:

-aumento della frazione di eiezione = riduzione dell’OH e viceversa

- pts con problemi di pompa cardiaca = pts OH

Aumento massa

ventricolare = aumento OH

Funzione renale e iperidratazione con BCM

0

500

1000

1500

2000

Diu

resi

resid

ua

-3 -2 -1 0 1 2 3 4 5 6

OH [L]

Bivariate Normal Ellipse P=0,950

OH [L]

Diuresi residua

Variable

1,228947

638,4211

Mean

1,74339

521,4145

Std Dev

-0,32197

Correlation

0,0487

Signif. Prob

38

Number

Correlation

Biv ariate Fit of Diuresi residua By OH [L]

-1

0

1

2

3

4

5

6

7

8

GF

R m

l/min

-3 -2 -1 0 1 2 3 4 5 6

OH [L]

Bivariate Normal Ellipse P=0,950

OH [L]

GFR ml/min

Variable

1,165714

2,36

Mean

1,795082

2,222174

Std Dev

-0,41823

Correlation

0,0124

Signif. Prob

35

Number

Correlation

Biv ariate Fit of GFR ml/min By OH [L]

Valutazione bcm e diuresi residua:

-aumento diuresi = riduzione dell’OH e viceversa

Conclusioni

• Il BCM è un apparecchio di facile e rapido utilizzo, leggero e trasportabile, poco costoso

• Validazioni e letteratura confermano l‘affidabilità e l‘utilità dell‘apparecchio sia in emodialisi che in dialisi peritoneale

• I dati ottenibili dalle misurazioni si dimostrano utili sia per la valutazione immediata che nel follow-up clinico dello stato di idratazione e nutrizione dei pazienti.