Cyrus M.

Calud, DVM, RN

Key challenges in ESRD patients management

Systemic Inflammation Response

Patient outcome
Malnourishment /Malnutrition

Cardiovascular Remodelling

Patient outcome and dialysis dose

The main aims of dialysis treatment are to prolong

patient survival, reduce morbidity and improve quality of life. However, despite many technical advances made over the last few years, morbidity and mortality of dialysis patients remain unacceptably high and their quality of life is often poor. . National Institute of Diabetes, Digestive, Kidney Diseases. (USRDS 2002 annual data report:
atlas of end-stage renal disease in the United States. Bethesda, MD, USA, 2002)

The delivered dose of dialysis can affect morbidity and

mortality of dialysis patients . (Port FK, Ashby VB, Dhingra RK, Roys EC, Wolfe RA. Dialysis
dose and body mass index are strongly associated with survival in hemodialysis patients. J Am Soc Nephrol 2002; 13: 10611066)

Patient outcome and dialysis dose

Relative risk of death (patients survival) improved with

higher dialysis dose (Kt/V)

Shinzato et al Kidney Int 1999; 55: 700-712 F.K. Port et al. JASN 13:1061-1066, 2002

Improved EPO dose response with higher Kt/V

E. Movilli, R. Maiorca et.al ,NDT:2001(16):111-114

Morbidity, number of days in the hospital and cost of

hospitalization are reduced with higher Kt/V

A. Sehgal et al. AJKD Vol 37, No 6 2001:pp 1223-1231

Todays recommendations for dialysis dose:

Adult non-diabetics:
minimal delivered dose spKt/V = 1.2 (Single Pool Variable Volume) minimal prescribed dose spKt/Vurea = 1.3 (SPVV)

Adult diabetics:
minimal required dose spKt/Vurea = 1.4 - in discussion, but not

officially recommended

Dialysis Outcome Initiative, Practical Guidelines, Am J Kidney Dis, 37 (Suppl 1), 2001

European Best Practice Guidelines

Guideline II.1.3
Based on the available evidence the minimum prescribed HD dose per

session for a thrice-weekly schedule should be:

urea eKt/V 1.20 (sp Kt/V 1.4)

EBPG Expert Group,NDT, Vol 17 (2002) Suppl. 7

Frequency of Measurement
Guideline 2 - Regular Measurement of the Delivered Dose of Hemodialysis (Evidence) The dialysis care team should routinely measure and monitor the delivered dose of hemodialysis The delivered dose of HD should be measured at regular intervals no less than monthly. The dose can be measured more frequently by using on-line methods (conductivity or ionic)

Measure of dialysis dose in practice

URR

- not all patients are able to afford blood tests on a monthly basis; not all computes regularly for URR
URR=100 (1 - Ct/C0) (2)
in which Ct is the postdialysis BUN and C0 is the predialysis BUN.

Kt/V

- not all RNs are interested to calculate the Kt/Vurea of patients

Kt/V = -Ln(R - 0.008 t)+(4 - 3.5 R) UF/W (1)
in which Ln is the natural logarithm; R is the postdialysis BUN predialysis BUN; t is the dialysis session length in hours; UF is the ultrafiltration volume in liters; and W is the patients postdialysis weight in kilograms

There is a readily available technology for us

The use of OCM has been validated and approved by CPGs

Electrolyte Clearance versus Urea electrolyte clearance [ml/min] Clearance aqueous solutions
Urea Clearance from blood samples [mL/min]

400

Electrolyte- Clearance [mL/min]

urea Steil H, et.al. ASAIO Trans 1993;39:M348-52 clearance [ml/min]

Kuhlmann U, Goldau R, Samadi N, Graf T, Orlandini G, Lange H: Accuracy and safety of online clearance monitoring based on conductivity variation. Abstr. EDTA 1999, 249

Comparison of two techniques

The conventional procedure today Blood samples
(expensive)

Aspects Kt/V > 1.2 ...1.8 Frequency

With OCM option Dialysate; K and t, (no additional costs) In every session Continuous, online None 5% Automatic

Monthly / quarterly

Retrospective
Staff, syringes, lab time cost and energy 6-8% Inconvenient Impractical and uncommon

Quality Control
Effort Accuracy of K Handling

Quality assurance

Standard!

Online Clearance Monitor (OCM)

No additional disposables or reagent (no additional cost)

Non invasive, One touch operation: extremely easy to use

Continuous and real time monitoring of k, kt (and calculated kt/v)

Continuous and real time estimate of plasma sodium concentration

Effective quality assurance tool verifying delivered dialysis dose each and all dialysis sessions

Intradialytic adjustment of treatment allows delivery of individualized dialysis

Online Clearance Monitor (OCM )

At effectively no additional work or cost we have a useful Quality Monitoring (QM) measure (Kt/V) for every (100%) of dialysis sessions.
It is however recommended that the OCM Kt/V be checked from time to time using standard laboratory methods.

Issues in Clinical Practice Nutrition

Malnutrition is a common among ESRD.
Around 10% are severely malnourished, and another 33% are

moderately malnourished (Maroni BJ. Nutrition and renal disease. In: Greenberg A, ed. Primer on
kidney diseases. San Diego, CA: Academic Presss; 1998:443.)

Moderate to severe malnutrition leads to weight loss and changes in body

composition, (reduced fat and muscle mass and an increase in total body fluids (TBW), specifically extracellular water (ECW).
Causes may include inadequate dialysis, decreased protein and caloric

intake due to loss of appetite, loss of amino acids in the dialysate, inflammation, catabolic factors and comorbid conditions (Kamyar Kalantar-Zadeh et.
alAmerican Journal of Kidney Diseases, Vol 42, No 5 (November), 2003: pp 864-881)

Malnutrition leads to increased mortality and morbidity

Assessment of nutritional status

Combination of science and an art

Procedure
Subjective Global Assessment Anthropometric measurement Laboratory tests (Biochemistry) Dual Energy X-Ray Absorptiometry (DEXA)

Advantage

Disadvantage

Requires time, expertise, Simple in principle and to and experience perform Inter-observer variance Confounders in lab results Accurate Requires scheduling Costly

Subjective Global assessment

Issues in Clinical Practice Fluids

One of the fundamental, yet most problematic, components of the dialysis

prescription is the patients estimated dry weight (EDW) The dry weight of each patient must be determined on trial-and error basis (Daugirdas, Blake, and Ing 2001) and is ideally evaluated every 2 weeks
hypertension in dialysis patients leading to structural changes of the heart muscles and blood vessels called cardiovascular remodeling

Sodium and volume excess is the predominant factor in the pathogenesis of

LVH is a strong and independent risk factor for cardiovascular morbidity and

mortality, is seen in more than 60% of end-stage renal disease patients.

The Mortality Risk of OH in HD Patient

Survival was retrospectively assessed in 269 prevalent HD patient from

3 European centers (Germany and Polland) after a follow-up at least 3.5 years
1
Hyperhydrated (n=58) nomohydrated (n=211)

OH<2.5 L Survival
0.8 0.6 0.4
ECW of 14%

OH>2.5 L
ECW of 15% p=0.023

20

40 Months

60

V Wizeman et al. Nephrol Dial Transplant 2009: 24; 1574-1579

The study indicate that HS is an important and independent predictor

of mortality in Chronic HD patients

Assessment of fluid status

Combination of science and art
Procedure Physical assessment Advantage Cheap Immediate Universally available Accurate Disadvantage Requires, expertise, experience, and prone to variation between observers Scheduling time Requires expertise Radiation exposure cost

Chest X - ray Ultrasound

Fluid Status Assessment

Road blocks in achieving normovolemia

Defining dry weight (normovolemia) Clinical assessment is insensitive and inadequate We need tools to improve diagnostic sensitivity

Achieving dry weight (normovolemia) Ultrafiltration (UF) intolerance is increasingly a problem We need tools to improve UF tolerance

Reduce UF requirement (a salt-intake issue) Improve hemodynamic stability (address issues such as thermal homeostasis) Understanding capillary refilling capacity of the patient

Limitations of current assessment approaches

Nutrition Fluid

- Cannot differentiate fats

- Cannot identify ECF/ICF

- Cannot determine

from muscles - Difficult to assess if weight gain is due to fat, muscles, or fluid

accurate overhydration volume

Risk factors confronting dialysis patients

Risk Factors
Cardiovascular Risk Factors
Salt intake Sodium overload Fluid intake Failure diagnose hypervolemia Failure achieve normovolemia Antihypertensive medications etc.

Nutritional Risk Factors

Inflammation intake of nutrient Loss of appetite protein catabolism Hyperparathyroidism Insulin resistance etc

Volume Overload Hypertension LVH CVD

Malnutrition ( fat/muscle mass ECV)

Mortality Risk of CKD patients

Available technologies that may help improve patients outcome

Selected Factors
Nutritional Status

Selected Technology
Body composition assessment - Body composition Monitor Biofeedback Control - Blood Volume Monitor (BVM) - Blood Temperature Monitor (BTM) Fluid Assessment - Body Composition Monitor (BCM)

Volume and Salt overload & Hypertension Intradialytic Hypotension

Body Composition Monitor (BCM)

The BCM measures and calculates

Overhydration pre-dialysis Body Mass Index (BMI)

Overhydration post-dialysis

Lean Tissue Index

Fat Tissue Index

Extracellular:Intracelluar Ratio Extracelluar water Intracellular water Total Body Water Lean Tissue Mass Relative Tissue Mass Body Cell Mass Adipose Tissue Mass Fat Mass Relative Fat Mass

BCM and patient management

The Body Composition Plot displays the development of the three compartments adipose tissue mass (ATM), lean tissue mass (LTM) and overhydration (OH) over time. In addition, the systolic blood pressure (BP sys) can be displayed, which allows the influence of overhydration on blood pressure to be identified. It is also easy to observe changes in LTM, ATM and the subsequent influence on overhydration. For a more detailed analysis of overhydration, please refer to the Overhydration Plot. The body composition can be viewed in more detail in the LTI FTI Plot.

http://www.bcm-fresenius.com/20.htm

BCM and patient management

The patients fluid status can be examined in more detail using the Overhydration Plot. The plot also provides post treatment overhydration which can be used to monitor changes in weight gain. Data can be easily compared against the green region representing the reference range of a healthy population.

http://www.bcm-fresenius.com/20.htm

BCM and patient management

It is well known that overhydration can lead to hypertension. However, underlying comorbidities can radically influence this relationship in individual patients.

The Hydration Reference Plot combines overhydration and systolic blood pressure in one graph.
It helps to assign patients to different regions regarding blood pressure and overhydration, which partly require different therapy approaches.

http://www.bcm-fresenius.com/20.htm

BCM and patient management

The BP pre Plot depicts the systolic and diastolic blood pressure before dialysis. The green area identifies the systolic reference area for a healthy population according to WHO standards. The green line at 70 mmHg marks the critical lower limit for the diastolic blood pressure.

http://www.bcm-fresenius.com/20.htm

BCM and patient management

This plot combines information about overhydration together with the patient's nutritional status. The green area indicates the reference area of a normal population with healthy kidneys (10th and 90th percentile).

http://www.bcm-fresenius.com/20.htm

Caveat
The BCM - Body Composition Monitor performs whole body measurements between hand and foot and therefore cannot assess regional differences in body

composition and fluid status. The device only detects interstitial fluid - a volume of fluid with a large cross-sectional area has little influence on the whole body impedance.
Body Composition Monitor has no approval for ICUs (electrical safety, conformity), but this will be realized in the future. Body Composition Monitor cannot be used in patients with stents or pacemakers (defibrillators) for safety reasons. Performance can be affected by artificial joints, pins or amputations.
http://www.bcm-fresenius.com/20.htm

Use the BCM in conjunction with your physical assessments and laboratory values!

Physiological Modules

Biofeedback mechanism that responds to patients tolerance to ultrafiltration

Blood Volume Monitor

Ultrafiltration and Hemodialysis

Blood volume reduction induced by ultrafiltration Critical vascular refilling during ultrafiltration

BV = UFR - VRR

Interstitial Fluid Space

Vascular Space

Critical!!! Vascular Refilling Rate

UF Rate > VR Rate

HYPOVOLEMIA

The Blood Volume Monitor (BVM)

The BVM monitors the changes of the relative blood

volume during the dialysis treatment.

The goal is to prevent excessive fluid removal, resulting

drop in blood pressure (hypotension)

The BVM control is performed in three zones:

Green zone (Non-critical Zone)
No control performed by the BVM.

Yellow zone (Control Performed)

The BVM prevents the blood volume from decreasing into the crit. RBV zone. If the RBV increases - the UFR will be raised again.

If the RBV reaches the dashed line, the message "Achieving the UF goal is uncertain will be displayed during the first half of the volume.

Red zone (Critical Zone)

The UFR is reduced up to 0ml/min. If the RBV increases the UFR will be raised again.

Blood Volume Monitor (BVM)

Reduced intradialytic complications

Hypotensive

episodes and the need for nursing interventions were significantly reduced when BVMcontrolled Uf was compared to standard UF.
Ronco C et al Kidney Int 2000; 58: 800-808

Improved Ultrafiltration tolerance, Less Hypotensive

Episodes with Blood Volume Control

Boer et al. Nieren und Hochdruckkrankh 31: 435, 2002

Added value (beyond hemodynamics)

Estimates of blood hemoglobin and hematocrit
Estimates! But as a tracking method reliable for direction and rate of

change where validated at certain frequency against lab values calibrate for each patient
In the era of EPO treatment and requirement for frequent monitoring
Frequent nonlab noninvasive estimates of Hb and/or HCT
Cost-offset? Assists in the estimation/determination of EDW

Blood Temperature Monitor

Average Temperature C

Diurnal Variation in Body Temperature Healthy Individuals versus HD Patients

38 37.5 37 36.5 36 35.5 35 34.5 34

Healthy individuals

HD pts.

6:30- 10:30- 3:30*P<0.001 vs. 3:30-4:30 group 7:30 11:30 4:30 am am pm

Pergola PE, Habiba NM, Johnson JM, Am J Kidney Dis. 2004 Jul;44(1):155-165 Mackowiak PA, Wasserman SS, Levine MM, JAMA. 1992 Sep 23-30;268(12):1578-1580

6 am 12 am 4 pm

Oral Predialysis Temperatures of 75 Patients

Oral temperature before dialysis (C)
N = 75 patients 3 measurement same week

Fixed Dialysate T36.5 C

Observations
Pergola PE, Habiba NM, Johnson JM, Am J Kidney Dis. 2004 Jul;44(1):155-165

Prepared by: Khoji Lugasan

High Dialysate Temperatures Cause Haemodynamic Instability (e.g. Dialysate 37.5C vs. 35.5C )
Literatures:
Ayoub A, Finlayson M, Nephrol Dial Transplant. 2004; 19(1):190-4

Fine A, Penner B, Am J Kidney Dis. 1996; 28(2): 262-5

Maggiore Q et al, Int J Artif Organs. 1995; 18(9): 518-25. Review. Jost CM et al, Kidney Int. 1993 Sep; 44(3): 606-12 Kerr PG, van Bakel C, Dawborn JK., Nephron. 1989; 52(2): 166-9

Marcen R et al, Nephron. 1988; 49(1): 29-32

Bazzato G et al, Kidney Int Suppl. 1985; 17: S161-5 Sherman RA et al, Am J Kidney Dis. 1985; 5(2): 124-7 Pizzarelli F et al, Int J Artif Organs. 1983; 6(1): 37-41

Coli U, et al, Trans Am Soc Artif Intern Organs. 1983; 29: 71-5
Maggiore Q et al, Trans Am Soc Artif Intern Organs. 1982; 28: 523-7 Maggiore Q et al, Proc Eur Dial Transplant Assoc. 1981; 18: 597-602

Conflicting physiological control mechanism in hemodialysis patients

Ultrafiltration Symptomatic Hypotension Surface heat loss Blood flow to skin
CONFLICT

Blood volume

Total peripheral resistance

VASOCONSTRICTION

VASODILATION

Blood flow to skin Surface heat loss Retain heat

Gotch et al ASAIO Trans 35:622-24, 1989

Total peripheral resistance

Core temperature + body heating by Dialysate temperature

Biofeedback Control
Patient responds to changes in treatment
Temperature Arterial

Temperature Venous

Prepared by: Khoji Lugasan

SET DESIRED EFFECT

CHANGE DIAL T IN DIRECTION TO DESIRED EFFECT

READ ART T READ ART T Hydraulic system

Dialyzer

BTM

Heater control

Patient

READ VEN T

READ DIAL T

Drain

Study done on the use of BTM

The BTM monitors and regulates changes in core body temperature to

prevent temperature-induced changes in vascular tone.

It provides the active control necessary to stabilise body temperature,

and reduces the frequency of haemodialysis sessions with hypotensive episodes.

Maggiore Q et al, Am J Kidney Dis. 2002 Aug;40(2):280-290

Prepared by: Khoji Lugasan

Studies with BTM demonstrate evidence for the maintenance of body temperature and BP during HD
Temp. (C)
37.5

Conventional dialysis
n=12 n=9 n=15

37.0

n=95

Tart begin of dialysis Tart end of dialysis

36.5 36.0

Isothermic/cold dialysis
Tart begin of dialysis Tart end of dialysis

35.5

35.0

Hemodynamic stability
Maggiore 2002 v.d. Sande 1999 Barendregt 1999 Kaufmann 1998 Barendregt JN, et al, Kidney Int. 1999 Jun;55(6):2598-608 Kaufman AM, et al, .J Am Soc Nephrol. 1998 May;9(5):877-883 Maggiore Q et al, Am J Kidney Dis. 2002 Aug; 40(2):280-290 Van der Sande FM, et al, Am J Kidney Dis. 1999 Jun;33(6):1115-1121

Prepared by: Khoji Lugasan

Additional function of BTM

Thermodilution Methods for Access & Cardiopulmonary Recirculation measurement

Existing technologies for better patient outcome

On-line Hemodiafiltration
maximizes diffusive and convective therapy for wider range of solute removal - reduction of pro-inflammatory cytokines

Ultrafilter and modern Water Treatment System, for

utrapure water and ultrapure dialysate

- reduce treatment bioincompatibility thus reduction of inflammatory response

Polysulfone dialyzer
- for biocompatible treatment, reduction of inflammatory response

Putting it all together

Online Clearance Monitor

(OCM)

Body Composition Monitor

(BCM)

Positive patient outcome

Blood Volume Monitor
(BVM)

Blood Temperature Monitor

(BTM)

Thank you!

Will entertain queries now...