Enjoy this nice review of Need for Daily Dialysis and journal club on the FHN trial

1. Outcomes of Daily Dialysis vs Conventional Hemodialysis Journal Club Prasanth Krish, MD Hofstra North Shore LIJ School of Medicine

2. Outline -How to measure HD dose – Kt/V -How much HD is “adequate?” -Is more HD better? -Can more HD be worse? -What markers of HD should we use? -What happens with increased frequency of HD?

3. Kt/V -A formula used to calculate the dose of hemodialysis -K= Clearance of dialyzer (obtained from manufacturer) -t= Time of dialysis (minutes) -V= Volume of distribution of urea (total body water)

4. Kt/V -”Single-pool:” (non-equilibrated) arterial blood drawn from extracorporeal circuit immediately after completion of dialysis session -”Double-Pool:” (equilibrated): blood drawn 30 minutes after HD session, to allow for urea from muscle to equilibrate with blood (~0.2 lower)

5. How much Dialysis is “Adequate?” -Is there a minimum target we should try to achieve? -Does more dialysis = better outcomes? -Are there disadvantages to more dialysis?

6. Is there a minimum amount of dialysis we should try to attain? NEJM 1993

7. Methods -Retrospective analysis of 13,473 pts -Stratified by URR (reference group 65-69%), with adjustments for age, sex, race, DM, MM, GN, PKD

8. Results

9. Does more dialysis yield better outcomes?

10. Methods -RCT of 1846 pts undergoing 3x/wk HD -4 groups: standard or high-dose dialysis, and low-flux or high-flux dialyzer -Primary outcome: death from any cause -Excluded patients with residual renal function >1.5ml/min or albumin <2.6

12. Good separation was achieved between the two groups

13. NO significant difference in primary or secondary outcomes

14. At 5 years, mortality in High-dose group was 4% lower, p value 0.53

15. At 5 years, mortality in High-flux group was 8% lower, p value 0.23

17. Can more HD be harmful? Kidney International 1999

18. Methods -3,009 patients underwent bioelectrical impedance analysis to determine total body water -Patients were stratified into 5 quintiles based on Kt/V

19. Results -Mortality was highest in group with highest URR -There were statistically significant differences in nutritional parameters, with highest Kt/V group having most severe malnourishment

20. Results -Re-assignment of groups based on Kt (removal of V) showed no increased risk of death. Higher Kt was associated with better nutritional status -Should Kt/V be used to assess the optimal dose of dialysis?

21. What markers of Dialysis should we be looking at? NCDS group – NEJM 1981 -Designed to evaluate clinical effects of different dialysis prescriptions -151 patients grouped by dialysis time (long or short) and BUN (high or low)

22. -Mortality and hospitalization rates were lower in low BUN group; dialysis time did not have significant effects -4 years later Gotch used this clinical data to show that Kt/V of urea was a marker of clinical outcome

23. Is Clearance of Urea (Kt/V) the Best Marker of Outcome? NDT 1998

24. Methods -Aim of study was to investigate effect of increasing dialysis frequency but not dialysis dose -13 patients on 3x/week hemodialysis for average of 9.7 years were switched to 6x/week dialysis, but weekly dose of Kt/V was kept constant

25. Results

26. Results

27. What happens when we increase the frequency of dialysis? JASN 1999:Clark et al used mathematical models to derive clearances and compared results to standard HD -If total dialysis time is kept constant, increased frequency results in mild increase in urea and MM clearance (3-6%)

28. -With long-duration/low-flow 3x/week, urea clearance is the same but MM clearance is increased -With daily long-duration/low-flow (ie nocturnal HD), there is markedly increased clearance of all solutes

29. Multiple clinical observations have shown improved outcomes in a wide range of categories: clearance of small and middle molecules, UF, quality of life, BP control, Anemia/EPO, LV mass, nutrition, lipidemia, hospitalizations, sleep, nutrition, fertility, survival

30. Potential drawbacks include cost and complications of access There have been no RCT . . . Until now!

32. Methods -A prospective, multicenter, randomized trial of 245 patients: 120 patients received 3x/week HD 125 patients received 6x/week HD -Obtaining the primary endpoint of death was not feasible due to sample size, therefore 2 composite endpoints were selected:

33. 1)Death or 12 month change in LV mass (determined via cardiac MRI) 2)Death or change in physical-health score -9 Secondary endpoints were chosen

39. Criticism -Insufficient power to comment on mortality -Exclusion of patients with residual function (>100 ml daily urine) -Sessions were performed in-center rather than at home