1. EDWARD WELSH MARCH 31 2010 Dialysis Adequacy (?)

2. Disclaimer

3. Adequate Equal to a requirement Barely satisfactory Acceptable Would you be happy with “adequate” therapy ?

4. Outline Basics of renal function History and Trials Formulae Problems

5. Kidney Function Maintain a steady state environment Continuous function and adjustment of metabolic parameters Filtration Secretion Metabolic Synthetic

6. Uremic Toxins Many known, many more unknown Small water soluble – urea Larger water soluble –guanidines Phosphates Protein bound compounds- cresols, drugs Middle molecules (MW>500 D)- greater than 20 compounds….AGE’s, B2M, PTH

7. Hemodialysis Replaces filtration Diffusive and convective losses Intermittent and short duration – 12 hours vs 168

8. Cont’ Removes volume, electrolytes, water soluble wastes and ( slowly) middle molecules and P04 No metabolism No secretion No synthetic function No removal of protein bound wastes

9. Urea Kinetic Modeling TAC, AUC Kt/V URR PRU eKt/V Single pool Kt/V Double pool V

10. Area under the Curve

11. History ? Quantity dialysis correlated with outcome Initially used nerve conduction, bleeding times, EEG - all poorly standardized Various toxins proposed/measured – middle molecules (B12 used as marker) Urea shown not to have toxic effects

12. First Study National Cooperative Dialysis Study (NCDS) published 1982 150 patients from 8 US centers 4 groups - 4 ½ hours and high TAC (36) - 4 ½ hours and low TAC (18) - 3 ½ hours and high TAC - 3 ½ hours and low TAC 3 runs per week, no real diet

13. Outcome Study stopped early – analysis revealed higher mortality in high TAC group Seemed to validate urea as useful marker Reanalysis data in 1985 – Gotch – led to UKM and Kt/V Kt/V of 0.9 considered minimum High TAC, 3 ½ hour group received Kt/V of 0.4 !

14. Oops Fixation on urea alone led to “high efficiency” dialysis with short runs mid 80’s to early 90’s in the US Poor outcomes Rest of world better outcomes – longer times Tassin - 3 runs per week, 8 hours per run

15. HEMO Trial 2002 ? Optimal dialysis dose 1846 patients Standard vs high dialysis dose and low vs high flux dialyzers Standard dose group - Kt/V = 1.25 High dose group - Kt/V = 1.65

16. Hemo outcomes

17. Outcome 17% mortality rate per year 40% due to cardiac events NO difference between any groups !

18. Risk of Death vs URR or Alb

19. URR

20. Albumin

21. Kt/V K= dialyzer clearance t = time on dialysis V = volume of patient body water

22. ? Calculate KT/V Need pre/post urea Existing patient data Treatment info All done same day Need computer program

23. Urea Reduction Ratio (URR) (Pre Urea – Post Urea ) /Pre Urea A single snapshot, easy to calculate PRU = URR x 100%

24. Prescribed vs Actual Prescribed - computerized estimation Actual – real run….. access that day, blood flow rates, treatment time

25. Timing When to measure post urea ? Too soon – post too low Single pool Recirculation Compartment dysequilibrium

26. Timing of Post Urea

27. Dialyzers Urea removed in relation to dialyzer surface area Larger surface area = greater removal urea Appropriate heparin to prevent clotting No reuse

28. Other factors Actual time on run Access type ? Recirculation Blood flow and dialysate flow rates – real vs entered Episodes hypotension…..

29. KDOQI guidelines 2006 Three runs a week Minimum run time 3 hours Kt?/V - target 1.4 with min 1.2 URR -target 70% with min 65% Kt/V is standard of practice

30. Netherlands Cooperative Study Residual renal function (RRF) Low Kt/V associated with mortality in anuric pts Need to consider both dialysis and renal Kt/V Excess interdialytic weight gain correlated with increase in mortality independent of Kt/V !

31. Conclusions Urea kinetics useful, but is only one measure of adequacy Other measures - Quality of life - Volume and BP control - Ca x Po4 - B2M….. LOOK at the patient !

32. Questions ?