Hemodialysis Adequacy and Mortality

1. Hemodialysis Adequacy Lutfi Alkorbi MD King Faisal Specialist Hospital Riyadh Saudi Arabia

2. Global dialysis population

3. Cardiovascular mortality in general population VS ESRD patients

4. Mortality in Hemodialysis Patients in Europe, Japan, and the United States DOPPS 2006

5. Dialysis adequacy and death The effect of dialysis dose on survival

6. First Randomised Controlled Trial In Dialysis The National Cooperative Dialysis Study (NCDS) was the first multicentric, randomized and controlled trial to investigate the impact of dialysis dose on patients' outcome. 160 patients were randomized to two different urea time averaged concentrations (TAC; 100 vs 50 mg/dl) and to two different treatment times (2.53.5 vs 4.55.5 h) and followed up for 6 months . NCDS 1980

7. First Randomised Controlled Trial In Dialysis NCDS 1980 Predialysis urea 38 vs 26 mmol. Dialysis 2.5-35h vs 4.5-5 h high kt/v and long dialysis high kt/v and short dialysis low kt/v and long dialysis low kt/v and short dialysis

8. Secondary analysis of NCDS A quantification of dialysis dose using spKt/V was first proposed by Gotch in a secondary analysis of NCDS data. In his analysis, probability of dialysis failure was higher for Kt/V 0.8 and abruptly decreased for Kt/V >0.9.

9. Higher Kt/V has better outcome Gotch FA,Sargent Kidney Int 1985;28:526 Kt/v=1.2

10. NCDS Conclusion Thus, according to NCDS patient morbidity and treatment failure are related to the dialysis dose

11. Why Should We Measure Dialysis Dose? There is a correlation between delivered dose of hemodialysis and patient morbidity and mortality Clinical symptoms are not reliable

12. Increasing dialysis dose improved survival dialysis dose Kidney Int 1996; 50:550

13. Measures of dialysis adequacy SpKt/V eKt/V StdKt/V URR

14. Hemodialysis Dose Measurement Kt/V K= dialyzer urea clearance L/h t = dialysis session length hr v = distribution volume of urea L URR

15. Urea reduction Ratio (URR) URR = 100 x (1-Ct/Co) Ct = postdialysis BUN Co = predialysis BUN

16. Urea Reduction Volume (URR) Simple Prediction of mortality Limitation: Does not account for the contribution of UF to dialysis dose Kt/V=1.1 (UF=0) Kt/v = 1.35 (UF=10%BW) URR=65

17. URR & Kt/V

18. Hemodialysis Dose Measurement The preferred method is by formal kinetic urea modeling K/DOQI 2006

19. Kt/V Computerized software Mathematical logarithm Kt/v = -Ln (R-0.008t)+(4-3.5xR) x UF W Ln = natural logarithm R = postdialysis BUN predialysis BUN UF = Ultrafiltration volume in liters W = Postdialysis weight in kg

20. BUN Sampling Predialysis Postdialysis Immediate predialysis Slow flow/stop pump

21. Urea Rebound Organs with low blood flow (skin, bone, muscles) may serve as reservoir for urea 70% of TBW is contained in organs that receive only 20% of CO So: during HD, there is loss of urea from well perfused areas, this result in in BUN over 60 minutes post dialysis.

22. Post Dialysis BUN Sampling Avoid 2 rebound: Early (<3min post dialysis) Access recirculation,begin immediately post hemodialysis and rebound in 20 seconds Cardiopulmonary recirculation, begin 20 seconds post hemodialysis and is completed in 2-3 minutes after slowing or stopping the blood pump. Late (>3 min) Completed within 30-60 minutes due to flow-volume disequilibrium.

23. Urea Rebound 65% rebound ( >50% is AR,15%CP,31% D)

24. Single-Compartment Fixed Volume Solute Kinetic Mode

25. Single-Pool vs Double-Pool Single-pool Does not account for urea transfer between fluid compartments With dialyzer clearance, urea removed from extracellular compartment can exceed transfer from intracellular compartment Urea rebound (30-60 min) So: Dialysis dose will be overestimated if this urea pool is large (underestimated of true V)

26. Two-Compartment Variable Volume Solute Kinetic Model

27. Equilibrated Kt/V eKt/v is 0.2 units less than single-pool kt/v, but it can be as great 0.6 unit less. For most patient, urea rebound is nearly complete in 15 minutes after hemodialysis but for minority, it may require up to 50-60 minutes The degree of rebound is high in small patient eKt/V= spKt/V - 0.6 x (spKt/V) / t + 0.03 (for arterial access) eKt/V= spKt/V - 0.47 x (spKt/V) / t + 0.02 (for venous access)

28. Minimum dialysis dose SpKt/V > 1.2 US eKt/V > 1.2 Europe StdKt/V 2.14

29. Daugirdas Formula

30. Daugirdas Formula

31. Prescribed vs. delivered Kt/V Prescribed Kt/V is a computerized estimation of what the patients Kt/V would be, based on the prescription Delivered Kt/V is actual results based on how the patient really dialyzed the day the kinetic labs were drawn

33. Discrepancies Between Delivered and Prescribed Dialysis Dose Delivered less than the prescribed : Low blood flow Inadequate dialyzer performance Low dialysate flow Dialysis machine programmed incorrectly Hemodialysis ended prematurely The predialysis BUN was drained after initiation of hemodialysis Access recirculation

34. Discrepancies Between Delivered and Prescribed Dialysis Dose Delivered Dose More than the Prescribed: Postdialysis BUN was drained from venous bloodline The post dialysis BUN was diluted with saline Small (V)

35. Low kt/v

36. How to improve clearance Blood flow Dialysate flow Dialyzer Duration frequency

37. Blood flow and Clearance

38. Blood flow and Clearance

39. Dialysate flow and clearance

40. The HEMO Study (2002)

41. The HEMO Study (2002) Standard dose group SpKt/V 1.3 eKt/V 1.16 URR 66.3 Dialysis T 190 min High dose group SpKt/V 1.7 eKt/V 1.53 URR 75.2 Dialysis T 219 min

42. The HEMO Study (2002) EKNOYAN et al N Engl j Med .2002;347:2010

43. Optimal Dialysis Anemia management Good nutrition BP control Adequate solute removal Fluid and electrolytes hemostasis BMD management Dialysis adequacy

44. Optimal Dialysis Anemia management Good nutrition BP control Adequate solute removal Fluid and electrolytes hemostasis BMD management Dialysis adequacy Kt/v

45. Filters Efficiency and Flux Efficiency : ability to achieve large small solute clearance with high blood flows (all filters are high efficiency these days) Flux : ability to achieve high middle molecule clearance and ultrafiltration rate (determined by the average pore size) Diffusion and Convection Diffusion : solutes move by diffusion between blocks of fluid separated by the membrane Convection : solutes move en mass with a block of fluid across the membrane (more effective for moving large molecules )

46. The HEMO Study (2002) EKNOYAN et al N Engl j Med.2002 ;347:2010

47. The MPO Study (2009)

48. Standard Kt/V

49. Standard Kt/V why Hemo study is negative ?

51. FHN

54. Better survival with long dialysis UpToDate

55. Residual renal function

56. Residual renal function

57. Time is important

60. What about hemodiafiltration ?