Clinical Monitoring Systems

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Ultrafiltration Management in Peritoneal
Dialysis
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Overview

• Fluid Management in Peritoneal Dialysis
• Kinetics of Peritoneal Ultrafiltration
• Icodextrin Chemistry Pharmacokinetic Profile
• Icodextrin Efficacy Profile Ultrafiltration
• Icodextrin Efficacy Profile Other Clinical
  Benefits
• Icodextrin Prescribing Considerations

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Rationale Maximise
Fluid Balance

• Primary function of renal replacement therapy
• PD represents optimal approach to this
  therapeutic goal
• Persistently high prevalence of hypertension and
  CV mortality among ESRD population underscores
  untapped potential of PD

Mujais, et al. Perit. Dial Int. 200020(suppl
4)S5-S21.
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Effective Fluid Management

• Established Clinical Benefits
• Controls blood pressure
• Lowers cardiovascular risk
• - LVH
• - CHF
• - Stroke
• Preserves GFR
• Prevents uremia-like symptoms
• Avoids acceleration of malnutrition, inflammation
  and atherosclerosis syndrome

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Fluid Balance

• A Clinical Challenge
• Maintaining edema-free state
• Dynamic nature of target weight
• Reliance on clinical judgment and indicators of
  volume status
• Individualized approach to fluid removal

Mujais, et al. Perit. Dial Int. 200020(suppl
4)S5-S21.
6
Optimizing Fluid Management

• Symptomatic fluid retention noted in 25 of PD
  patients1
• Lower extremity edema 98.6
• Pleural effusions 76.1
• Pulmonary congestion 80.3
• Similar clinical observations in Japan,2 the
  Netherlands,3 and Sweden4

1Tzamaloukas, et al. J Am Soc Nephrol.
19956198-206. 2Kawaguchi, et al. Kidney Int.
199752S105-S107. 3 Ho-dac-Pannekeet, et al.
Perit Dial Int. 199717144-150. 4Heimbürger, et
al. Perit Dial Int. 199919S83-S90.
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Current PD StatusHigh Prevalence of Elevated BP
Frankenfield, et al. Kidney Int.
1999551998-2010.
Cocchi, et al.
Nephrol Dial Transplant. 1999141536-1540.
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Volume Reduction BP Control
47 hypertensive CAPD patients
Na restriction
20 normotensive
3 normotensive with enalapril
27 hypertensive
Na restriction ? UF
4 normotensive with enalapril
17 normotensive
7 hypertensive
3 hypertensive
37 normotensives in total achieved with volume
control alone
Gunal, et al. Am J Kidney Dis. 200137588-593.
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Fluid OverloadAn Underappreciated Cause of CV
Mortality
Causes of Death in Dialysis Patients1

• The majority of dialysis patients die of cardiac
  causes 36 present with CHF1,2
• Hypervolemia and hypertension remain important
  underlying causes3

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Cardiac Other known Infection Unknown Cerebrovascu
lar Malignancy
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47
4
16
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1USRDS 1997 Annual Report Data. 2Stack, et al. Am
J Kidney Dis. 200138992-1000. 3Lamiere, et al.
Perit Dial Int. 200021206-211.
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Fluid Overload vs UF FailureAn Important
Distinction

• Fluid overload is a common clinical syndrome with
  multiple causes
• It is the inability to maintain target weight and
  oedema free state
• UF failure is a pathophysiologic characterisation
  of one of the causes of the clinical syndrome
• Distinction between syndrome and cause determines
  the intervention to be taken

Mujais, et al. Perit. Dial Int. 200020(suppl
4)S5-S21.
11
Causes of Fluid Overload in PD

• Excessive salt water intake
• Loss of residual renal urine volume
• Cardiac disease
• Non compliance with PD prescription
• Insufficient use of hypertonic exchanges
• Dialysate leak
• Catheter malfunction
• Hyperglycaemia
• UF failure

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Current UF ManagementHampered by Complexity

• Dietary counseling
• Compliance issues
• May complicate management
• Limiting renal excretion1
• Gradual decline to anuria
• Failure to respond to diuretics
• Peritoneal Ultrafiltration (UF)
• Challenge of the long dwell

Medcalf, et al. Kidney Int. 2001591128-1133.
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The Long Dwell in PD
APD
Long dwell
Cycles 1 to 4
Manual exchange
Manual exchange
Manual exchange
CAPD
Long dwell
Nighttime
Daytime

• APD and CAPD both have long dwells
• In APD, even high-dose nighttime exchanges
  involve long dwells of 8-12 hours

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Value of the Long Dwell

• Toxin removal
• Small solutes fluid flow-dependent
• Middle and large MW toxins time-dependent
• Continuously wet abdomen required for therapy
  success
• Lifestyle
• Logistic burden and compliance
• Realistic therapy imperative

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ISPD Ad Hoc CommitteeUF Management in PD
The most frequently ignored principles in PD
that lead to UF difficulties are the need to
avoid long dwells with glucose in high
transporters and balancing glucose concentration
and dwell time.
Peritoneal Dialysis International, 2000
Mujais, et al. Perit Dial Int. 200020(suppl
4)S5-S21.
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4.25 DextroseLong Dwell Limitations

• Rapid glucose absorption and loss of UF potential
  and small solute clearance
• Negative net UF
• Fluid overload
• Systemic metabolic effects and obesity
• Local biocompatibility issues and impact on
  peritoneal membrane structure and function

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Assessing Volume Status Proactive Monitoring and
Evaluation

• Achieving and maintaining target weight
• (goal normal BP, with euvolemia)
• Review of dietary compliance/guidelines
• Monitoring residual renal function
• Evaluating solute clearance
• Awareness of peritoneal function

Mujais, et al. Perit. Dial Int. 200020(suppl
4)S5-S21.
18
Redefining what is a dry weight

• Minimal definition
• Oedema-free body weight
• Maximal definition
• Weight below which further fluid removal results
  in signs and symptoms of hypovolemia
• Clinical definition
• Between minimal and maximal definitions with
  resolution of volume-dependent derangements in
  homeostasis
• (explained please make notes on this!)

Mujais, et al. Perit. Dial Int. 200020(suppl
4)S5-S21.
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ISPD GuidelinesOptimal Fluid Management in PD

• Routine standardized monitoring and awareness of
  PET status
• Dietary counseling of appropriate salt and water
  intake
• Protection of RRF
• Loop diuretics if RRF present
• Patient education for enhanced compliance
• Preservation of peritoneal membrane function
• Hyperglycemia control

International Society for Peritoneal
DialysisPeritoneal equilibration test
Residual renal function.
Mujais, et al. Perit Dial Int. 200020(suppl
4)S5-S21.
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Definition of UF Failure

• Drain volume lt2400ml after 4 hour dwell with 2L
  4.25 glucose
• 4.25 is preferred to 2.5 PET because the
  greater osmotic challenge of a 4.25 dwell is
  more likely to be discriminating in the
  assessment of UF

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UFF Classification

• Type I
• High transport status
• Rapid loss of glucose osmotic gradient
• Commonest increases with time
• Type II
• Low transport status
• Loss of peritoneal surface area
• Not common

• Type III
• High lymphatic flow rate
• By exclusion of other types only
• Prevalence unknown
• Type IV
• Aquaporin dysfunction
• Rare

Overall, UFF occurs in lt3 of patients in Year
1, In 9.5 by 3 years and in 30 by 6 years
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UF FailureA structured diagnostic approach to
managing a patient
UF FailureA Structured Diagnostic Approach
REVERSIBLE CAUSES
RRF
PERITONEUM
Dietary indiscretion, compliance
Appropriate Rx
Mechanical causes
Low transport
Low-average or high-average transport
Dwell time
Leaks
Deficient education
Obstructions
Dialysate tonicity
High transport
Complex regimen
Entrapment
Malposition
Residual renal function
Burn-out
Mujais, et al. Perit Dial Int. 200020(suppl
4)S5-S21.
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UF FailureEvaluating the Clinical Syndrome
Clinical Syndrome
Initial Evaluation for Reversible Causes
Evaluation of Peritoneal Membrane Function
UF Response
Small Solute Transport
Mujais, et al. Perit Dial Int. 200020(suppl
4)S5-S21.
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UF FailureIdentifying Reversible Causes
Clinical Syndrome
Initial Evaluation for Reversible Causes
Dietary Non-Compliance
Appropriate Prescription
Mechanical Problems
Mujais, et al. Perit Dial Int. 200020(suppl
4)S5-S21.
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UF FailureAssessing UF Response
Clinical Syndrome
Initial Evaluation for Reversible Causes
Evaluation of Peritoneal Membrane Function
UF Response
Drain Volume lt2400 mL / 4 hr
Drain Volume gt2400 mL / 4 hr
Mujais, et al. Perit Dial Int. 200020(suppl
4)S5-S21.
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UF FailurePeritoneal Membrane Function
UF Response
Drain Volume lt2400 mL/4 hr
Small Solute Profile
Low Transport D/P Cr lt0.5
High Transport D/P Cr gt0.81
High-Avg or Low-Avg 0.81gt D/P Cr gt0.5
Mujais, et al. Perit Dial Int. 200020(suppl
4)S5-S21.
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UF FailureLow Drain, Low Transport
Drain Volume lt2400 mL/4 hr
Small Solute Profile
Low Transport D/P Cr lt0.5

• Disruption of peritoneal space, adhesions, etc.
• Peritoneography

Mujais, et al. Perit Dial Int. 200020(suppl
4)S5-S21.
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UF FailureLow Drain, High-Avg or Low-Avg
Transport
Drain Volume lt2400 mL/4 hr
Small Solute Profile
High-Avg or Low-Avg Transport 0.5lt D/P Cr lt0.81

• Mechanical problems
• Tissue absorption
• Aquaporin deficiency

Mujais, et al. Perit Dial Int. 200020(suppl
4)S5-S21.
29
UF FailureLow Drain, High Transport
Drain Volume lt2400 mL/4 hr
Small Solute Profile
High Transport D/P Cr gt0.81

• Inherently high transport
• Recent peritonitis
• High transport of long-term PD

Mujais, et al. Perit Dial Int. 200020(suppl
4)S5-S21.
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Therapeutic Approaches Universal Measures
Low Drain, High Transport CAPD?APD Icodextrin for long dwells
Low Drain, High-Avg or Low-Avg Transport Icodextrin for long dwells Dextrose for short dwells
Low Drain, Low Transport High-dose loop diuretics with RRF Adjunctive HD or transfer to HD
Mujais, et al. Perit Dial Int. 200020(suppl
4)S5-S21.
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Guidelines for improving UF

• CAPD
• Avoidance of long dwells with low glucose
  concentrations
• Use of nighttime exchange devices
• Tailoring prescriptions to transport profiles
  determined by PET
• APD
• Avoidance of long dwells with low glucose
  concentrations
• Use of short day dwells even when no additional
  exchangesneeded for clearance

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Volume Control Algorithm
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Volume Control Algorithm
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Volume Control Algorithm
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Volume Control Algorithm
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Volume Control Algorithm
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High transport outcome
High transporters Efficient membranes for small
solute clearancebut may have difficulty with
ultrafiltration, especially during the long dwell
Recent studies (Davis1 and Churchill2) have
shown that high transporters had a worse
prognosis probably due to a more difficult fluid
balance management
1 Davis et al. KI 1999 Vol 54 p 2207 2217 2
Churchill et al JASN 1998 - Vol 9 1285 - 1292
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Therapeutic approaches

• Inherent high transporters
• APD icodextrin for the long dwell is the
  recommended therapeutic approach
• Recent peritonitis
• Several studies have indicated that UF during an
  episode of peritonitis can be satisfactorily
  achieved with the use of icodextrin
• High transport during long term PD
• For patients with a net UF less than 400 mL/4
  hours and a high transport profile of small
  solute clearance, APD and icodextrin for the long
  dwell are the recommended therapeutic approaches

Mujais, et al. Perit Dial Int. 200020(suppl
4)S5-S21.
39
Summary 12 Strategies to improve Volume
Management in PD

1. Start PD earlier
2. Protect residual renal function
3. Use high-dose loop diuretics o maintain urine
   output
4. Educate patients regarding salt and water intake
   and regarding significance of oedema, weight
   gain, etc
5. Appropriate use of hypertonic solutions
6. Awareness of PET status

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Summary 12 Strategies to improve Volume
Management in PD

• 7. Consider APD in high and high average
• transporters
• 8. Night exchange device in CAPD if night t im
  dwell is reabsorbed
• 9. Short day dwells on APD long enough to give
  good clearance and short enough to give good UF
• 10. Icodextrin for long dwells in CAPD APD
• 11. Frequent reassessment of the patients target
  weight
• 12. Anti-hypertensives only when volume removal
  has failed to reduce BP.

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Case Study