1. Peritoneal Dialysis Adequacy & Prescription Management

2. 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

3. Improving patient lifetime on therapy
Access
Adequacy
QoL
Fluid control
Nutrition
Compliance
Infection control

4. Components of Prescription Management
Fixed Parameters
Adjusted Parameters
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

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 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

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 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.

9. 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

10. The peritoneal equilibration test (PET)
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

11. The peritoneal equilibration test (PET)
Drain volumes correlate positively with dialysate glucose and
negatively with D/P creatinine at 4 hours

12. Membrane transport type.

13. Calculation of Peritoneal Urea Clearance

14. Calculation of peritoneal urea clearance
= x 7
= 2.02

15. Calculation of Peritoneal Creat. Clearance

16. Calculation of Peritoneal Creat Clearance
= 10.7 x x 7
= 59 l/wk
Normalise to BSA = CCl x 1.73/ patients BSA
Normalised weekly CCl = 59 l/wk/1.73 m2

17. A standard patient?
2.0
10 l
1.0
35l
= x 7
= 2.0

18. Problems arise for large body weights
Optimizing peritoneal dialysis dose
Schedule dwell times to maximise clearance
Increase dialysis dose by increasing drain volumes
Problems arise for large body weights

19. 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 CRF
JASN 10: S287-S321, 1999

20. 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
Increase number of exchanges
Increase
fill
volume

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 care
Varied 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 noted
Varied glucose concentrations and Extraneal® are advised to use in order to meet the required UF of min.1 L
APD* 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 Time
and Transport
Transport Solute Cl UF Prescription
Rapid Short dwell
High A CAPD/CCPD
Low A CAPD/CCPD
Low Long Dwells
> Always maximize fill volumes

25. Common prescription errors - CAPD
mismatch dwell time and transport type
inappropriately short daytime dwell
inappropriate infused volumes
inappropriate glucose concentration for nighttime dwell

26. 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

27. 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.

28. 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

29. Study Design

30. Peritoneal CrCl L/wk/1.73 m2 95% Confidence Limits on Means
ADEMEX: Treatment Characteristics
Months After Randomization
Mean Trends in Peritoneal CrCl
Peritoneal CrCl L/wk/1.73 m2
95% Confidence Limits on Means
p<.001

31. 95% Confidence Limits on Means
ADEMEX: Treatment Characteristics
Months After Randomization
Mean Trends in pKt/V
Peritoneal Kt/V
95% Confidence Limits on Means
p<.001

32. ADEMEX: Primary Outcome
% Patient Survival
RR(Treated:Control)=1.00
95% CI: (0.80, 1.24)
Months on Study

33. 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)

34. Recommended Total Solute Clearance Targets
CAPD Kt/V CCr/1.73m2
NKF-DOQI L
NKF-DOQI 2000
L&LA L
HA&H L
Canadian guidelines
L & LA L
HA & H L
Renal Assoc - UK L
EDTA-ERA (Peritoneal)

35. Prescription Modification

36. Prescription Modification

37. Prescription Modification

38. Prescription Modification

39. Prescription Modification

40. APD - Increasing Clearance
Increase fill volumes
Add a daytime exchange
Increase Time on Cycler
Increase Number of Nighttime Exchanges

41. APD - Increasing Clearance
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

42. APD - Increasing Clearance
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

43. APD - Increasing Clearance
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

44. APD - Increasing Clearance
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

45. Initiate Therapy Measure Clearances Adjust Therapy
Solute Control Algorithm
Initiate Therapy
Measure Clearances
Adjust Therapy

46. Monitoring frequency KT/V and Creat.clr: PET
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
Clinical Practice Guidelines of the Canadian Society of Nephrology for treatments of Patients with CRF
JASN 10: S287-S321, 1999

47. 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

48. 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
Clinical Practice Guidelines of the Canadian Society of Nephrology for treatments of Patients with CRF
JASN 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.