1. What is the Role of Peritoneal Dialysis in Optimising ESRD Patient Outcomes?

2. PD: Optimising Outcomes? Slow Progression of Renal Disease Prevent Additional Injury to Kidneys Manage Co-morbid Conditions – Cardiovascular Disease – Diabetes – Anemia Preserve Vascular Access Site Maintain Proper Nutrition Pre-dialysis Education for Patient Pre-ESRDESRD Preserve Residual Renal Function Prevent Additional Injury to Kidneys Delay Long Term Complications Manage Co-morbid Conditions – Cardiovascular Disease – Diabetes – Anemia Preserve/Maintain Vascular Access Site Maintain Proper Nutrition Patient Social and Employment Rehabilitation Blood Purification Electrolyte and Acid Base Equilibrium Goals Before and Following Initiation of Dialysis Initiation of Dialysis

3. PD: Optimising Outcomes? Non-Medical Factors that Impact on ESRD Modality Selection Financial/reimbursement Physician experience with both therapies Patient and family understanding of modality options Availability of resources (staff, finance, space, etc) Social factors Cultural habits Nissenson AR, Kidney Int, 1993; 43 (Suppl. 40):S120-S127

4. PD: Optimising Outcomes? Modality Selection and Distribution Where Do We Want To Be?

5. PD: Optimising Outcomes? Total survival is more important than survival on each therapy HD TX PD “What patients want to know is which sequence of RR modalities will increase their survival as long as possible & this with the best Quality of Life” Van Biesen 2000

6. PD: Optimising Outcomes? Integrated Care Approach “Start renal replacement therapy in ESRD patients with PD, transfer them to HD when problems with PD occur, and transplant them when the possibility exists” Lameire N, et al, Seminar of Uro-Nephrology, (1999)

7. PD: Optimising Outcomes? Integrated care concept: Patient survival and quality of life are two very important factors in the selection of a dialysis modality The majority of studies have compared the two modalities as « competitors » rather than as « complementary » techniques Since every RRT has a technical « drop-out », it is very likely that a patient will need several modalities during his lifetime and transfer from one technique to another will often be needed.

8. PD: Optimising Outcomes? Integrated Therapy - questions Does the physician believe that all RRT modalities should be made available to each patient ? Should the patient have a free choice? Does each RRT modality have a role to play during the lifetime of a patient with renal failure ?

9. PD: Optimising Outcomes? Reasons for Modality Switch Van Biesen WE, et al, J Am Soc Nephrol 2000;11:116-125 Access CV Poor BP Personal Peritonitis Social Adequacy Leakage of Problems Problems Control Choice Exit-Site Problems or UF Dialysis Fluid Access CV Poor BP Personal Peritonitis Social Adequacy Leakage of Problems Problems Control Choice Exit-Site Problems or UF Dialysis Fluid Haemodialysis to Peritoneal Dialysis Peritoneal Dialyisis to Haemodialysis Percent of patients 50% 25% 14% 40% 25% 12% 11% 23% 0 10 20 30 40 50

10. PD: Optimising Outcomes? Integrated ESRD Care Residual Renal Function Hemodialysis Creatinine Clearance (ml/min) 20 15 10 5 0 Time on Dialysis Initiation of Dialysis Peritoneal Dialysis Transplant PD

11. PD: Optimising Outcomes? Challenges for PD Can PD stand on an equal footing with HD? If PD is to be used for RRT, it must give equivalent results both for mortality and morbidity as does HD

12. PD: Optimising Outcomes? Where is PD today? Similar survival to HD PD is treatment of choice for children Peritonitis and exit-site infection rates have been reduced Clearance targets can be achieved Lower costs than HD Good treatment prior to transplantation

13. PD: Optimising Outcomes? PD as the Initial Form of Renal Replacement Therapy Better initial survival Preserves residual renal function Effective blood pressure and volume control PD  Transplant: reduced risk of early acute renal failure Reduced risk of being infected by a blood borne virus Delays the use of HD blood access sites Quality of life

14. PD: Optimising Outcomes? Initial Survival Advantage of PD - Canadian Results Patient Survival (%) Months 10663 patients P<0.001 Fenton AJKD 30:334-42, 1997

15. PD: Optimising Outcomes? HD PD to HD Van Biesen JASN 2000; 11:116-25 Comparing Survival of “Integrated Care” Patients with HD Patients

16. PD: Optimising Outcomes? Possible Causes Better preservation of residual renal function in PD. Moist JASN 11:556-64, 2000 The ”unphysiology” of HD. Kjellstrand KI 7(S2):530-36, 1975 Lopot NDT 13(S6):74-78, 1998 Monday HD mortality increased 58% relative to other days. Bleyer KI 55:1553-9, 1999

17. PD: Optimising Outcomes? PD as the Initial Form of Renal Replacement Therapy Better initial survival Preserves residual renal function Effective blood pressure and volume control PD  Transplant: reduced risk of early acute renal failure Reduced risk of being infected by a blood borne virus Delays the use of HD blood access sites Quality of life

18. PD: Optimising Outcomes? Preservation of residual renal function Lysaght et al, ASAIO Trans, 1991; 37:598-604 Time on therapy in months Residual Creatinine Clearance (ml/min) 0 1 2 3 4 5 0612182430364248 CAPD (n=58) HD (n=57)

19. PD: Optimising Outcomes? Preservation of residual renal function Lang et al, PDI 21:52-57, 2001

20. PD: Optimising Outcomes? Risk of RRF Loss Odds Ratio Multivariate Analysis1843 patients * p<0.05 ** p<0.01 *** p<0.001 ** *** * * ** *** * Moist JASN 11:556-565, 2000

21. PD: Optimising Outcomes? What are the benefits of preserving residual renal function? Reduces Mortality Contributes to total solute clearance (1 ml/min CrCl = 10 liter CrCl/week) Facilitates volume control Allows for more liberal diet and fluid intake Provides endocrine functions Erythropoietin production Ca++, phosphorus and vitamin D homeostasis Improves  2-microglobulin and middle molecule clearance Improves nutritional status Improves QoL Increases total Na removal Davies, S., 2000

22. PD: Optimising Outcomes? Causes of RRF Preservation in PD Avoidance of Dehydration HD: production of inflammatory mediators by blood contact McCarthy JASN 4:367, 1993 Lysaght ASAIO Trans 37:598-604, 1991 Better clearance of middle molecules, lipophilic and proteinbound toxins.

23. PD: Optimising Outcomes? n=33 n=21 n=24 n=16 0 1000 2000 3000 4000 5000 6000 Healthy Control HD PD CRF Without dialysis Serum CRP, ng/ml Serum CRP Values Haubitz et al. PDI 16(2): 158-162, 1996 ** *# *p<0.01 vs. control #p<0.01 vs. PD

24. PD: Optimising Outcomes? PD as the Initial Form of Renal Replacement Therapy Better initial survival Preserves residual renal function Effective blood pressure and volume control PD Transplant: reduced risk of early acute renal failure Reduced risk of being infected by a blood borne virus Delays the use of HD blood access sites Quality of life

25. PD: Optimising Outcomes? Difference in BP Control by Dialysis Modality The prevalence of hypertension in HD patients is approximately 80% vs. approximately 50% in PD patients. “Hypertension is not optimally controlled in HD and PD, but is better controlled in PD than HD” “Lower blood pressure in PD patients is attributed to the more successful achievement of dry weight by slower ultrafiltration” Mailloux AJKD 1998; 32(S3), S120-S141 NKF Taskforce on CV Disease

26. PD: Optimising Outcomes? Effect of CAPD Blood Pressure Control Months % Variation From Baseline Saldanha AJKD 1993; 21:184-188 Patients transferred from HD to PD (n = 67) -15 -10 -5 0 5 10 15 20 0123456789101112 Weight Hematocrit Blood Pressure * * * * ****** * * * p<0.05

27. PD: Optimising Outcomes? Modality and Cardiovascular Disease Canziani MD, et al, Artificial Organs, 1995; 19:241-244

28. PD: Optimising Outcomes? PD as the Initial Form of Renal Replacement Therapy Better initial survival Preserves residual renal function Effective blood pressure and volume control PD Transplant: reduced risk of early acute renal failure Reduced risk of being infected by a blood borne virus Delays the use of HD blood access sites Quality of life

29. PD: Optimising Outcomes? Transplantation and the role of PD Graft function immediately after transplantation is important 24% of PD patients have delayed graft function (DGF) vs. 50% of HD patients* Patients with delayed graft function have a 10% decreased graft survival Reduced need of post-transplantation dialysis PD patients have lower usage of immunosuppressive medication* PD patients suffer a lower incidence of late infections* * Perez Fontan M, Perit Dial Int, 1996, 16: 48-54

30. PD: Optimising Outcomes? Dialysis Modality and Delayed Graft Function GroupPDHDP Value % anuric in first 24 h 8.311.9<0.001 % dialysis in first week 20.028.6<0.001 % treated for rejection 12.012.90.20 % non-functioning graft at discharge 13.714.80.14 Bleyer et al. J Am Soc Nephrol 10:154-159, 1999

31. PD: Optimising Outcomes? PD as the Initial Form of Renal Replacement Therapy Better initial survival Preserves residual renal function Effective blood pressure and volume control PD Transplant: reduced risk of early acute renal failure Reduced risk of being infected by a blood borne virus Delays the use of HD blood access sites Quality of life Cheaper

32. PD: Optimising Outcomes? Hepatitis B & C 309 patients Brazil High background prevalence of Hepatitis B & C Seroconversion partly related to blood transfusion (p=0.05) Seroconversion (%/yr) P<0.001 P<0.02 Cendoroglo Neto NDT 10:240-46, 1995

33. PD: Optimising Outcomes? Modality and Hepatitis C Pereira B. Kidney Int, 1997; 51:981-999

34. PD: Optimising Outcomes? Why lower risk of HCV in PD? Lower requirement for blood transfusion than HD patients The absence of a vascular access site and extracorporeal blood circuit reduces the risk for parenteral exposure to the virus PD is a home therapy and it offers a more isolated environment Pereira KI 1997; 51:981-999

35. PD: Optimising Outcomes? PD as the Initial Form of Renal Replacement Therapy Better initial survival Preserves residual renal function Effective blood pressure and volume control PD Transplant: reduced risk of early acute renal failure Reduced risk of being infected by a blood borne virus Delays the use of HD blood access sites Quality of life

36. PD: Optimising Outcomes? Total lifespan of vascular access Creation and maintenance of adequate vascular access remains a major problem in HD ESRD patients have compromised cardiovascular systems Any strategy that can augment the total lifespan of vascular access is of value Additional time is “won” by starting PD

37. PD: Optimising Outcomes? Modality and EPO - Japan Shinzato T, et al, Kidney Int, 1999; 5:700-712

38. PD: Optimising Outcomes? Modality and EPO - Europe House AA, et al, Nephrol Dial Transplant, 1998; 13:1763-1769

39. PD: Optimising Outcomes? Modality and Transfusions House AA, et al, Nephrol Dial Transplant, 1998; 13:1763-1769

40. PD: Optimising Outcomes? What is the Role of PD in Optimising ESRD Patient Outcomes? Influenced by: –Availability of modality options –Profile of co-morbidities –Patient choice and self-care motivation –Physician experience and knowledge –Outcome evidence

41. PD: Optimising Outcomes? Following an integrated strategy of dialysis that uses PD as an initial therapy then HD may improve total patient survival and preserve societal resources which could be reallocated to treat more of the continuously increasing population of ESRD patients. Conclusion Dratwa 1999