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
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
<ul><li>Results </li></ul><ul><li>Higher intensity of dialysis provides no mortality benefit </li></ul><ul><li>Higher flux dialyzer provides no mortality benefit </li></ul><ul><li>Mortality rates in this sample group was similar to the rest of the USA </li></ul>
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
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 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:
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