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