Outcomes of Daily Dialysis vs
Conventional Hemodialysis
Journal Club Prasanth Krish, MD
Hofstra North Shore LIJ School of Medicine
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?
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)
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)
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?
Is there a minimum amount of dialysis we should try to attain?
NEJM 1993
Methods
-Retrospective analysis of 13,473 pts
-Stratified by URR (reference group 65-69%), with adjustments for age, sex, race, DM, MM, GN, PKD
Results
Does more dialysis yield better outcomes?
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
Good separation was achieved between the two groups
NO significant difference in primary or secondary outcomes
At 5 years, mortality in High-dose group was 4% lower, p value 0.53
At 5 years, mortality in High-flux group was 8% lower, p value 0.23
Results
-Higher intensity of dialysis provides no mortality benefit
-Higher flux dialyzer provides no mortality benefit
-Mortality rates in this sample group was similar to the rest of the USA
Can more HD be harmful?
Kidney International 1999
Methods
-3,009 patients underwent bioelectrical impedance analysis to determine total body water
-Patients were stratified into 5 quintiles based on Kt/V
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
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?
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)
-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
Is Clearance of Urea (Kt/V) the Best Marker of Outcome?
NDT 1998
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
Results
Results
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%)
-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
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
Potential drawbacks include cost and complications of access
There have been no RCT . . . Until now!
Methods-A prospective, multicenter, randomized trial of 245 patients:120 patients received 3x/week HD125 patients received 6x/week HD
-Obtaining the primary endpoint of death was not feasible due to sample size, therefore 2 composite endpoints were selected:
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
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