peritoneal dialysis peritoneal dialysis adequacy & prescription management

Peritoneal Dialysis

Peritoneal Dialysis Adequacy &

Prescription Management

Peritoneal Dialysis

Background

• Target small solute clearances have been based upon assumptions that peritoneal and renal clearances are added together

• Renal small solute clearances are directly correlated with patient survival

• There have been no randomized, controlled interventional trials examining the role of increases in peritoneal small solute clearances on patient survival

Peritoneal Dialysis

Improving patient lifetime on therapy

Access

Fluid control

Adequacy

NutritionCompliance

QoL

Infection control

Peritoneal Dialysis

• Disease Process

• Lifestyle

• Body Size

• Residual Renal Function (RRF)

• Peritoneal Membrane

• Fill Volume

• Number of Exchanges

• Dwell Time

• Efficient Use of Total 24 Hours

• Glucose Concentration

Fixed Parameters Adjusted Parameters

Components of Prescription Management

Peritoneal Dialysis

Adequacy Targets have changed over the last decade

Creat.clr KT/V (l/week)

• In 1992: 40 1.5• In 1995: 50 1.7• In 1997: 60 2.0• In 1999: 60 2.0 (high-avg/high transporters)

50 (low/low-avg transporters)

• In 2001* 50 1.7• Ultrafiltration starts to get an increased focus

compared to earlier – 1L total water removal/day

*European PD guidelines, published 2001

Peritoneal Dialysis

What is Clearance?

• Clearance is the total amount of body fluid completely cleared of a solute during a certain time

• ml/min• L/week

• Ex: Creatinine clearance = 50 l/week means:

50 L of body fluid is totally cleared for creatinine during a week

Peritoneal Dialysis

Targets for solute clearance

Suggested impact on outcome

50 60

1.7 2.0

CrCl

Kt/V

Peritoneal Dialysis

The peritoneal equilibration test (PET)

• Semiquantitative assessment of peritoneal membrane transport function

• Assess rates of solute equilibration between peritoneal capillary blood and dialysate

• Uses the ratio of solute concentrations in dialysate and plasma (D/P) at specific times to signify the extent of equilibration

• Performed using a standardized method, using standard solutions (2.27% glucose)

Twardowski ZJ, Nolph KD, Khanna R et al Perit Dial Bull 1987;7:138.

Peritoneal Dialysis

Clinical applications of the PET

• peritoneal membrane transport classification• predict dialysis dose• choose peritoneal dialysis regime• monitor peritoneal membrane function• diagnose acute membrane injury• diagnose causes of inadequate ultrafiltration• diagnose causes of inadequate solute clearance• estimate D/P ratio of a solute at a particular time

Peritoneal Dialysis


• following a standard overnight exchange• drain to dryness• instill 2.27% 2000 ml glucose bag• roll patient to ensure mixing• sample PD fluid at time 0, 2, 4 hours• blood test (assume blood concentrations

constant)• drain out at 4 hours and measure drain volume

Peritoneal Dialysis


Drain volumes correlate positively with dialysate glucose and negatively with D/P creatinine at 4 hours

Peritoneal Dialysis

Membrane transport type.

0

10

20

30

40

50

60

L LA HA H

Peritoneal Dialysis

Calculation of Peritoneal Urea Clearance

Drain No Dwell time Drain Vol. Drain urea

1 285 2500 11.9

2 285 2500 12.2

3 315 2625 10.0

4 597 2500 14.3

Plasma urea 14.4 mmol/l Total drain vol = 10125 ml

Volume of distribution

31595 ml Average drain urea = 12.7

Peritoneal Dialysis

7 )

(/ x

aplasma ure

readiaysate ux

ondistributiofvolume

volumedrainvKtweekly

714.1

12.7

31595

10125/ xxvKtweekly

= 0.288 x 7= 2.02

Calculation of peritoneal urea clearance

Peritoneal Dialysis

Calculation of Peritoneal Creat. Clearance

Drain No Dwell time

Drain Vol. Drain creatinine

1 285 2500 804

2 285 2500 800

3 315 2625 817

4 597 2500 1017

Plasma creatinine

1091 umol/l

Total drain vol = 10125 ml

Body surface area

1.737 m2 Ave drain creat = 859.5 umol/l

Peritoneal Dialysis

Calculation of Peritoneal Creat Clearance

7

)( x

creatinineplasma

creatininedialysatexvolumedraintotallclearancecreatinineweekly

= 10.7 x 0.788 x 7= 59 l/wk

Normalise to BSA = CCl x 1.73/ patients BSA

Normalised weekly CCl = 59 l/wk/1.73 m2

Peritoneal Dialysis

A standard patient?

7medistn volu

medrain volu clearance ureatarget x

P

Dx

2.0 10 l

35l

1.0

= 0.286 x 7= 2.0

Peritoneal Dialysis

Optimizing peritoneal dialysis dose

7medistn volu

medrain volu clearance ureatarget x

P

Dx

Problems arise for

large body weights

Increase dialysis dose by

increasing drain volumes

Schedule dwell times to

maximise clearance

Peritoneal Dialysis

Treatment guidelines – a summary

• Patients with BSA> 1.7m2 or body weight >65 kg• Routinely prescribed 2.5L fill volume

• Patients with BSA> 2 m2 or body weight >80 kg• Routinely prescribed 3 L fill volume

• Patients requiring 5 day exchanges should use a night time exchange device to deliver the 5th exchange

• Patients on APD should do one or more day time exchanges (unless small BSA or high RRF)

Clinical Practice Guidelines of the Canadian Society of Nephrology for treatments of Patients with CRFJASN 10: S287-S321, 1999

Peritoneal Dialysis

Main principles behind the APD guidelines• Patients with higher D/P require an increased number of exchanges during

the night• Patients with higher BSA require higher fill volume per exchange• Anuric patients are advised to have an extra day exchange (OCPD)• Extraneal is encouraged to be used in all patients during a long day well

as it can improve the UF and clearance of patients

L(D/P <0.5)

LA(D/P 0.5-0.65)

HA(D/P 0.65-0.81)

H(D/P > 0.81)

Small (<1.71 BSA)

Medium (1.71 - 2.0BSA)

Large (>2.0 BSA)

Increase number of exchanges

Increase fill

volume

Peritoneal Dialysis

Overview of guidelinesRRF >2 ml/min

Low D/P Low Avg. D/P High Avg. D/P High D/P

SmallBSA

3x2.5L +2x2L or 1x2.5 L

3x2.5L+2L

4x2L+2L

4-5x2L+2L

MediumBSA

3x3L+2x2L or 1x2.5L

3x2.5-3L+2.5L

4x2.5L+2L

4x2.5L or 5x2L+2L

LargeBSA

3x3L+2x2.5L

3x3L +3L

4x3L+ 2.5L

4-5x2.5L+2.5L

All prescriptions include 9 hours overnight treatment. If targets are over achieved, reducing therapy time at night can be an option. Monitor with careVaried glucose concentrations and Extraneal® are advised to use in order to meet the required UF of min.1 L

Peritoneal Dialysis

Overview of guidelines RRF <2 ml/min

Low D/P Low Avg. D/P High Avg. D/P High D/P

SmallBSA

CAPD, Quantum

APD *3x2.5L (9-10 hrs)+2x2.5L

3x2.5*+2x2L

4x2L+2x2L

4-5x2L+2x2L

MediumBSA

CAPD, Quantum orHDAPD *3x3L (9-10 hrs)+2x3L

3x3L+2x2.5L

4x2.5L+2x2.5L

4 x 2.5L or 5 x2L+ 2x2L

LargeBSA CAPD, Quantum or

HD

CAPD, Quantum orHDAPD*3x3L (9-10 hrs)+ 2x3L

4 x 3L+2x2.5L

4-5x2.5L+2x2.5L

All prescriptions include 9 hours overnight treatment if not otherwise notedVaried glucose concentrations and Extraneal® are advised to use in order to meet the required UF of min.1 LAPD* For these patient groups, APD therapy will probably not reach both KT/V and Creat clr. targets. Monitor with care. Two day time exchanges can be beneficial for motivated patients in order to meet targets.

Peritoneal Dialysis

Impact of larger CAPD volumes on total CCl versus a 5th exchange (calculated).

No of exchanges

4 5 4

Total CCr (l/1.73m2)

56.7 58.9 66.1

Drain volume

2000 2000 2500

Assume 70 kg male, anuria, 4 hr D/P = 0.65, BSA 1.73m2, 2l UF.

Peritoneal Dialysis

Transport Solute Cl UF Prescription

Rapid ++++ + Short dwell

High A +++ ++ CAPD/CCPD

Low A ++ +++ CAPD/CCPD

Low + ++++ Long Dwells

> Always maximize fill volumes

Relationship Between Dwell Timeand Transport

Peritoneal Dialysis

Common prescription errors - CAPD

• mismatch dwell time and transport type

• inappropriately short daytime dwell

• inappropriate infused volumes

• inappropriate glucose concentration for nighttime dwell

Peritoneal Dialysis

Common prescription errors - APD

• inappropriate use of a dry day

• inappropriately long drain times

• failure to increase target dose to account for intermittent therapy

• failure to consider a CAPD exchange during the day to increase clearance

Peritoneal Dialysis

ADEMEX

• ADEMEX (ADEquacy of PD in MEXico) is a randomized, active controlled, prospective trial

• Hypothesis tested: increases in peritoneal clearance of small solutes improves the PD patients’ survival

• The primary outcome was mortality.

Peritoneal Dialysis

ADEMEX Summary of Design

Patient Numbers• 965 Mexican patients current or new to dialysis from 24

participating centers were randomized • 484 Control

• 481 Treated

• Initial recruitment started on June 1, 1998 • First patient randomized July 9, 1998

• Follow-up through May 6, 2001 • A minimum follow-up of two years following enrollment

Peritoneal Dialysis

Study Design

Control GroupC o ntin ue on s tan dard th erapy

4 x 2L p er d ayN = 484

In tervention Group2 p rescriptio n adju stm en ts

A im p CrC l > 60 L /w eek /1.73 m 2N = 481

Random izationcentralized

ScreeningpCrCl < 60 L /w eek/1.73 m 2

Peritoneal Dialysis

ADEMEX: Treatment Characteristics

Months After RandomizationMea

n T

ren

ds

in P

erit

on

eal

CrC

l

Peritoneal CrCl L/wk/1.73 m2

95% Confidence Limits on Means

p<.001

Peritoneal Dialysis

ADEMEX: Treatment Characteristics

Months After Randomization

Mea

n T

ren

ds

in p

Kt/

V

Peritoneal Kt/V95% Confidence Limits on Means

p<.001

Peritoneal Dialysis

p=0.9842

RR(Treated:Control)=1.00

95% CI: (0.80, 1.24)

Months on Study

% P

atie

nt S

urv

ival

ADEMEX: Primary Outcome

Peritoneal Dialysis

ADEMEX: Conclusions

• There was no difference in patient survival with variations in peritoneal small solute clearance within ranges achievable in current clinical practice.

• Survival remained similar between the two groups even after adjusting for factors known to be associated with mortality in patients on PD (age, diabetes, albumin, nPNA, anuria)

Peritoneal Dialysis

Recommended Total SoluteClearance Targets

CAPDCAPD Kt/VKt/V CCr/1.73mCCr/1.73m22

NKF-DOQI 1997NKF-DOQI 1997 2.0 60 L

NKF-DOQI 2000NKF-DOQI 2000L&LA 2.0 50 LHA&H 2.0 60 L

Canadian guidelinesCanadian guidelinesL & LA 2.0 50 LHA & H 2.0 60 L

Renal Assoc - UKRenal Assoc - UK 1.7 50 LEDTA-ERA 1.7 (Peritoneal)

Peritoneal Dialysis

Prescription Modification

Peritoneal Dialysis

APD - Increasing Clearance

• Increase fill volumes

• Add a daytime exchange

• Increase Time on Cycler

• Increase Number of Nighttime Exchanges

Peritoneal Dialysis


• Increase fill volumes• Effective means of improving clearance• Minimum impact on patient lifestyle• Adjust nighttime exchanges first• Use 2.0L or greater whenever possible

• Add a daytime exchange • Increase Time on Cycler• Increase Number of Nighttime Exchanges

Peritoneal Dialysis


• Increase fill volumes• Add a daytime exchange

• This is a very effective means of improving clearance• HomeChoice can be programmed to deliver the midday

exchange

• Increase Time on Cycler• Increase Number of Nighttime Exchanges

Peritoneal Dialysis


• Increase fill volumes• Add a daytime exchange• Increase Time on Cycler

• Cycler time can be extended to 10 hours• Increasing cycler time with a constant number of

exchanges increases dwell time which increases clearance

• Increase Number of Nighttime Exchanges

Peritoneal Dialysis


• Increase fill volumes• Add a daytime exchange• Increase Time on Cycler• Increase Number of Nighttime Exchanges

• May increase clearance, but only if time on cycler is also increased

Peritoneal Dialysis

Initiate Therapy

Measure Clearances

Adjust Therapy

Solute Control Algorithm

Peritoneal Dialysis

Monitoring frequency

• KT/V and Creat.clr:• Within 6-8 weeks after commencing dialysis• Every subsequent 6 month• If patients clinical status changes unexpectedly, or if

prescription is altered, take supplemental clearance measurements

• PET• Within 6 weeks of initiating PD• Repeat if unexpected changes in peritoneal UF occur


Peritoneal Dialysis

Making monitoring of adequacy easier

Using a software program makes monitoring easier:

• Automated calculations of creat clearance, KT/V, nPNA

• Reporting function gives easy overview of one patient or whole patient population

• Easy to identify problem patients where actions might be needed

• Track and document improvements over time

Peritoneal Dialysis

Auditing clinical outcomes in PD

• Monitor patient and technique survival in all large programs

• Monitor % of patients in all PD programs who fail to achieve targets

• Record % of patients in all PD programs with inadequate nPNA values and severe hypoalbuminemia

• A good program will have 80-85% of patients achieving adequacy targets

• Review the proportions of patients exceeding targets every 3-6 months


Peritoneal Dialysis

Conclusion.

• There is uncertainty about the target clearance in PD

• Patient management in peritoneal dialysis involves much more than small solute clearance – of particular importance are for example residual renal function and ultrafiltration volume, as well as the other complex of factors central to holistic management of renal failure patients.

peritoneal dialysis peritoneal dialysis adequacy & prescription management

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