2 BackgroundTarget small solute clearances have been based upon assumptions that peritoneal and renal clearances are added togetherRenal small solute clearances are directly correlated with patient survivalThere have been no randomized, controlled interventional trials examining the role of increases in peritoneal small solute clearances on patient survival
3 Improving patient lifetime on therapy AccessAdequacyQoLFluid controlNutritionComplianceInfection control
4 Components of Prescription Management Fixed ParametersAdjusted ParametersDisease ProcessLifestyleBody SizeResidual Renal Function (RRF)Peritoneal MembraneFill VolumeNumber of ExchangesDwell TimeEfficient Use of Total 24 HoursGlucose Concentration
5 Adequacy Targets have changed over the last decade Creat.clr KT/V (l/week)In 1992:In 1995:In 1997:In 1999: (high-avg/high transporters) (low/low-avg transporters)In 2001*Ultrafiltration starts to get an increased focus compared to earlier – 1L total water removal/day*European PD guidelines, published 2001
6 What is Clearance?Clearance is the total amount of body fluid completely cleared of a solute during a certain timeml/minL/weekEx: Creatinine clearance = 50 l/week means:50 L of body fluid is totally cleared for creatinine during a week
7 50 60 1.7 2.0 CrCl Kt/V Targets for solute clearance Suggested impact on outcome
8 The peritoneal equilibration test (PET) Semiquantitative assessment of peritoneal membrane transport functionAssess rates of solute equilibration between peritoneal capillary blood and dialysateUses the ratio of solute concentrations in dialysate and plasma (D/P) at specific times to signify the extent of equilibrationPerformed using a standardized method, using standard solutions (2.27% glucose)Twardowski ZJ, Nolph KD, Khanna R et al Perit Dial Bull 1987;7:138.
9 Clinical applications of the PET peritoneal membrane transport classificationpredict dialysis dosechoose peritoneal dialysis regimemonitor peritoneal membrane functiondiagnose acute membrane injurydiagnose causes of inadequate ultrafiltrationdiagnose causes of inadequate solute clearanceestimate D/P ratio of a solute at a particular time
10 The peritoneal equilibration test (PET) following a standard overnight exchangedrain to drynessinstill 2.27% 2000 ml glucose bagroll patient to ensure mixingsample PD fluid at time 0, 2, 4 hoursblood test (assume blood concentrations constant)drain out at 4 hours and measure drain volume
11 The peritoneal equilibration test (PET) Drain volumes correlate positively with dialysate glucose andnegatively with D/P creatinine at 4 hours
18 Problems arise for large body weights Optimizing peritoneal dialysis doseSchedule dwell times to maximise clearanceIncrease dialysis dose by increasing drain volumesProblems arise for large body weights
19 Treatment guidelines – a summary Patients with BSA> 1.7m2 or body weight >65 kgRoutinely prescribed 2.5L fill volumePatients with BSA> 2 m2 or body weight >80 kgRoutinely prescribed 3 L fill volumePatients requiring 5 day exchanges should use a night time exchange device to deliver the 5th exchangePatients 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
20 Main principles behind the APD guidelines Patients with higher D/P require an increased number of exchanges during the nightPatients with higher BSA require higher fill volume per exchangeAnuric 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 patientsIncrease number of exchangesIncreasefillvolume
21 Overview of guidelines RRF >2 ml/min 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
22 Overview of guidelines RRF <2 ml/min 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.
23 Assume 70 kg male, anuria, 4 hr D/P = 0.65, Impact of larger CAPD volumes on total CCl versus a 5th exchange (calculated).Assume 70 kg male, anuria, 4 hr D/P = 0.65,BSA 1.73m2, 2l UF.
24 > Always maximize fill volumes Relationship Between Dwell Timeand TransportTransport Solute Cl UF PrescriptionRapid Short dwellHigh A CAPD/CCPDLow A CAPD/CCPDLow Long Dwells> Always maximize fill volumes
25 Common prescription errors - CAPD mismatch dwell time and transport typeinappropriately short daytime dwellinappropriate infused volumesinappropriate glucose concentration for nighttime dwell
26 Common prescription errors - APD inappropriate use of a dry dayinappropriately long drain timesfailure to increase target dose to account for intermittent therapyfailure to consider a CAPD exchange during the day to increase clearance
27 ADEMEXADEMEX (ADEquacy of PD in MEXico) is a randomized, active controlled, prospective trialHypothesis tested: increases in peritoneal clearance of small solutes improves the PD patients’ survivalThe primary outcome was mortality.
28 ADEMEX Summary of Design Patient Numbers965 Mexican patients current or new to dialysis from 24 participating centers were randomized484 Control481 TreatedInitial recruitment started on June 1, 1998First patient randomized July 9, 1998Follow-up through May 6, 2001A minimum follow-up of two years following enrollment
30 Peritoneal CrCl L/wk/1.73 m2 95% Confidence Limits on Means ADEMEX: Treatment CharacteristicsMonths After RandomizationMean Trends in Peritoneal CrClPeritoneal CrCl L/wk/1.73 m295% Confidence Limits on Meansp<.001
31 95% Confidence Limits on Means ADEMEX: Treatment CharacteristicsMonths After RandomizationMean Trends in pKt/VPeritoneal Kt/V95% Confidence Limits on Meansp<.001
32 ADEMEX: Primary Outcome % Patient SurvivalRR(Treated:Control)=1.0095% CI: (0.80, 1.24)Months on Study
33 ADEMEX: ConclusionsThere 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)
34 Recommended Total Solute Clearance Targets CAPD Kt/V CCr/1.73m2NKF-DOQI LNKF-DOQI 2000L&LA LHA&H LCanadian guidelinesL & LA LHA & H LRenal Assoc - UK LEDTA-ERA (Peritoneal)
40 APD - Increasing Clearance Increase fill volumesAdd a daytime exchangeIncrease Time on CyclerIncrease Number of Nighttime Exchanges
41 APD - Increasing Clearance Increase fill volumesEffective means of improving clearanceMinimum impact on patient lifestyleAdjust nighttime exchanges firstUse 2.0L or greater whenever possibleAdd a daytime exchangeIncrease Time on CyclerIncrease Number of Nighttime Exchanges
42 APD - Increasing Clearance Increase fill volumesAdd a daytime exchangeThis is a very effective means of improving clearanceHomeChoice can be programmed to deliver the midday exchangeIncrease Time on CyclerIncrease Number of Nighttime Exchanges
43 APD - Increasing Clearance Increase fill volumesAdd a daytime exchangeIncrease Time on CyclerCycler time can be extended to 10 hoursIncreasing cycler time with a constant number of exchanges increases dwell time which increases clearanceIncrease Number of Nighttime Exchanges
44 APD - Increasing Clearance Increase fill volumesAdd a daytime exchangeIncrease Time on CyclerIncrease Number of Nighttime ExchangesMay increase clearance, but only if time on cycler is also increased
46 Monitoring frequency KT/V and Creat.clr: PET Within 6-8 weeks after commencing dialysisEvery subsequent 6 monthIf patients clinical status changes unexpectedly, or if prescription is altered, take supplemental clearance measurementsPETWithin 6 weeks of initiating PDRepeat if unexpected changes in peritoneal UF occurClinical Practice Guidelines of the Canadian Society of Nephrology for treatments of Patients with CRFJASN 10: S287-S321, 1999
47 Making monitoring of adequacy easier Using a software program makes monitoring easier:Automated calculations of creat clearance, KT/V, nPNAReporting function gives easy overview of one patient or whole patient populationEasy to identify problem patients where actions might be neededTrack and document improvements over time
48 Auditing clinical outcomes in PD Monitor patient and technique survival in all large programsMonitor % of patients in all PD programs who fail to achieve targetsRecord % of patients in all PD programs with inadequate nPNA values and severe hypoalbuminemiaA good program will have 80-85% of patients achieving adequacy targetsReview the proportions of patients exceeding targets every 3-6 monthsClinical Practice Guidelines of the Canadian Society of Nephrology for treatments of Patients with CRFJASN 10: S287-S321, 1999
49 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.