ultrafiltration management in peritoneal dialysis

Peritoneal Dialysis

Ultrafiltration Management

in Peritoneal Dialysis

Peritoneal Dialysis

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

Peritoneal Dialysis

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. Mujais, et al. Perit. Dial IntPerit. Dial Int. 2000;20(suppl 4):S5-S21.. 2000;20(suppl 4):S5-S21.

Peritoneal Dialysis

Effective Fluid ManagementEstablished Clinical BenefitsEstablished Clinical Benefits

Controls blood pressureLowers cardiovascular risk

- LVH- CHF- Stroke

Preserves GFRPrevents uremia-like symptomsAvoids acceleration of malnutrition, inflammation and

atherosclerosis syndrome

Peritoneal Dialysis

Fluid Balance

A Clinical ChallengeMaintaining edema-free state

Dynamic nature of target weight

Reliance on clinical judgment and indicators of volume status

Individualized approach to fluid removal


Peritoneal Dialysis

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

11Tzamaloukas, et al. Tzamaloukas, et al. J Am Soc Nephrol.J Am Soc Nephrol. 1995;6:198-206. 1995;6:198-206. 2 2Kawaguchi, et al. Kawaguchi, et al. Kidney Int.Kidney Int. 1997;52:S105-S107. 1997;52:S105-S107. 33 Ho-dac-Pannekeet, et al. Ho-dac-Pannekeet, et al. Perit Dial Int.Perit Dial Int. 1997;17:144-150. 1997;17:144-150. 44Heimbürger, et al. Heimbürger, et al. Perit Dial Int.Perit Dial Int. 1999;19:S83-S90. 1999;19:S83-S90.

Peritoneal Dialysis

Current PD Status

High Prevalence of Elevated BP

05

10152025303540

Normal High-normal Stage 1 Stage 2 Stage 3

JNC6 BP Category

Num

ber o

f Pat

ient

s (%

) I talyUSA

Frankenfield, et al. Frankenfield, et al. Kidney Int.Kidney Int. 1999;55:1998-2010. 1999;55:1998-2010. Cocchi, et al. Cocchi, et al. Nephrol Dial Transplant.Nephrol Dial Transplant. 1999;14:1536-1540. 1999;14:1536-1540.

Peritoneal Dialysis

Volume Reduction & BP Control

Gunal, et al. Gunal, et al. Am J Kidney DisAm J Kidney Dis. 2001;37:588-593.. 2001;37:588-593.

47 hypertensive CAPD patients

20 normotensive20 normotensive

Na restriction & Na restriction & UF UF

3 normotensive 3 normotensive with enalaprilwith enalapril

17 normotensive*17 normotensive* 4 normotensive 4 normotensive with enalaprilwith enalapril

7 hypertensive

3 hypertensive

*37 normotensives in total achieved with volume control alone *37 normotensives in total achieved with volume control alone

Na restrictionNa restriction

27 hypertensive

Peritoneal Dialysis

Fluid Overload

An Underappreciated Cause of CV Mortality

• The majority of dialysis patients die of cardiac causes; 36% present with CHF1,2

• Hypervolemia and hypertension remain important underlying causes3

Causes of Death in Dialysis Causes of Death in Dialysis PatientsPatients11

CardiacCardiacOther knownOther knownInfectionInfectionUnknownUnknownCerebrovascularCerebrovascularMalignancyMalignancy

47%

20%

7%

4%

16%

6%

11USRDS 1997 Annual Report Data. USRDS 1997 Annual Report Data. 22Stack, et al. Stack, et al. Am J Kidney DisAm J Kidney Dis. . 2001;38:992-1000. 2001;38:992-1000. 33Lamiere, et al. Lamiere, et al. Perit Dial IntPerit Dial Int. 2000;21:206-211. . 2000;21:206-211.

Peritoneal Dialysis

Fluid Overload vs UF Failure

An 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


Peritoneal Dialysis

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

Peritoneal Dialysis

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. Medcalf, et al. Kidney Int. Kidney Int. 2001;59:1128-1133.2001;59:1128-1133.

Peritoneal Dialysis

The Long Dwell in PD

Nighttime DaytimeAPD and CAPD both have long dwellsAPD and CAPD both have long dwellsIn APD, even high-dose nighttime exchanges involve long In APD, even high-dose nighttime exchanges involve long

dwells of 8-12 hoursdwells of 8-12 hours

Long dwell

Long dwell Manual exchange

Manual exchange

Manual exchange

Cycles 1 to 4

APDAPD

CAPDCAPD

Peritoneal Dialysis

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

Peritoneal Dialysis

ISPD Ad Hoc Committee

UF 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. Mujais, et al. Perit Dial IntPerit Dial Int. 2000;20(suppl 4):S5-S21.. 2000;20(suppl 4):S5-S21.

Peritoneal Dialysis

4.25% Dextrose

Long 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

Peritoneal Dialysis

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

Assessing Volume Status

Proactive Monitoring and Evaluation


Peritoneal Dialysis

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!)


Peritoneal Dialysis

ISPD* GuidelinesOptimal Fluid Management in PD

Routine standardized monitoring and awareness of PET† status

Dietary counseling of appropriate salt and water intakeProtection of RRF‡

Loop diuretics if RRF presentPatient education for enhanced compliancePreservation of peritoneal membrane functionHyperglycemia control


*International Society for Peritoneal Dialysis;*International Society for Peritoneal Dialysis;††Peritoneal equilibration test; Peritoneal equilibration test; ‡‡Residual renal function.Residual renal function.

Peritoneal Dialysis

Definition of UF Failure

• Drain volume <2400ml 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

Peritoneal Dialysis

UFF Classification

Type I High transport status Rapid loss of glucose

osmotic gradient Commonest; increases

with timeType 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 <3% of patients in Year 1,In 9.5% by 3 years and in 30% by 6 years

Peritoneal Dialysis

UF FailureA Structured Diagnostic Approach


REVERSIBLE CAUSESRRF* PERITONEUM

Appropriate Rx

Dwell time

Dialysate tonicity

Dietaryindiscretion,compliance

Mechanicalcauses

Deficienteducation

Complexregimen

Burn-out

Leaks

Obstructions

Entrapment

Malposition

Low-average or high-average

transport

High transport

*Residual renal function*Residual renal function

Low transport

UF FailureA structured diagnostic approach to managing a patient

Peritoneal Dialysis

UF FailureEvaluating the Clinical Syndrome

Clinical Syndrome

Initial Evaluation for Reversible Causes

Evaluation of Peritoneal Membrane Function

UF Response

Small Solute Transport


Peritoneal Dialysis

UF FailureIdentifying Reversible Causes

Clinical Syndrome


Dietary Non-Compliance

Appropriate Prescription

Mechanical Problems


Peritoneal Dialysis

UF FailureAssessing UF Response

Clinical Syndrome


Evaluation of Peritoneal Membrane Function

UF Response

Drain Volume<2400 mL / 4 hr

Drain Volume>2400 mL / 4 hr


Peritoneal Dialysis

UF FailurePeritoneal Membrane Function

Drain Volume<2400 mL/4 hr

Small Solute Profile

Low TransportD/P Cr <0.5

High TransportD/P Cr >0.81

High-Avg or Low-Avg0.81> D/P Cr >0.5

UF Response


Peritoneal Dialysis

UF FailureLow Drain, Low Transport

Low TransportD/P Cr <0.5

Disruption of peritoneal space, adhesions, etc. Peritoneography




Peritoneal Dialysis

UF FailureLow Drain, High-Avg or Low-Avg Transport

High-Avg or Low-Avg Transport0.5< D/P Cr <0.81

Mechanical problems Tissue absorption Aquaporin deficiency




Peritoneal Dialysis

UF FailureLow Drain, High Transport



High TransportD/P Cr >0.81

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


Peritoneal Dialysis

Therapeutic Approaches

Universal MeasuresLow Drain, High Transport

– CAPDAPD– 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


Peritoneal Dialysis

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 exchanges

needed for clearance

Peritoneal Dialysis

Volume Control Algorithm

SaltF lu id

DietaryEvaluation

VolumeTrend

Meds/effects

ResidualRenal Function

Long dw ellTotal UF

PET

PeritonealPrescrip tion

Interventions

Peritoneal Dialysis


QOL issuesInventory control

Delivered dose

EvaluateCom pliance

localized vs.generalized

Trend

CharacterizeEdem a

Outflow obsLeaks/hernia

CatheterFunction

Interventions

Peritoneal Dialysis


ReviewPET

Modifydw ell tim e

Modifytonicity

Alternateosm otic agent

N egativenet UF

O ptionalm in im ize 4 .25%

Positivenet UF

EvaluateLong dw ell U F

24 hr UF

Perit. P rescription

Peritoneal DialysisVolume Control Algorithm

I ncreasecycle num ber

Modifyton icity

I ncreasecycler tim e

Considerfi ll volum e

Cycler

Modifyton icity

Consideradditional exchange

Considerfi ll volum e

CAPD

O ptim izeshort dw ell U F

Peritoneal Dialysis


Nephrotoxins?

<200 m l/day

ConsiderD iuretics

>200 m l/day

UrineOutput

Peritoneal Dialysis

High transport & outcomeHigh 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

60

70

80

90

100

0 6 12 18 24

% S

urvi

ving

Time in Months

HighHigh AverageLow AverageLow

Impact on outcomes in PD

1 Davis et al. KI 1999 Vol 54 p 2207 – 2217 2 Churchill et al JASN 1998 - Vol 9 1285 - 1292

Peritoneal Dialysis

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


Peritoneal Dialysis

Summary: 12 Strategies to improve Volume Management in PD

1. Start PD earlier2. Protect residual renal function3. Use high-dose loop diuretics o maintain urine

output4. Educate patients regarding salt and water

intake and regarding significance of oedema, weight gain, etc

5. Appropriate use of hypertonic solutions6. Awareness of PET status

Peritoneal Dialysis

7. Consider APD in high and high average transporters8. Night exchange device in CAPD if night –t im dwell

is reabsorbed9. Short day dwells on APD – long enough to give

good clearance and short enough to give good UF10. Icodextrin for long dwells in CAPD & APD11. Frequent reassessment of the patient’s target

weight12. Anti-hypertensives only when volume removal has

failed to reduce BP.

Summary: 12 Strategies to improve Volume Management in PD

Peritoneal Dialysis

Case Study

ultrafiltration management in peritoneal dialysis

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