EDWARD WELSHMARCH 31 2010

Dialysis Adequacy (?)

Disclaimer

Adequate

Equal to a requirement

Barely satisfactory

Acceptable

Would you be happy with “adequate” therapy ?

Outline

Basics of renal function

History and Trials

Formulae

Problems

Kidney Function

Maintain a steady state environmentContinuous function and adjustment of

metabolic parameters

FiltrationSecretionMetabolicSynthetic

Uremic Toxins

Many known , many more unknown

Small water soluble – ureaLarger water soluble –guanidinesPhosphatesProtein bound compounds- cresols , drugs

Middle molecules (MW>500 D)- greater than 20 compounds….AGE’s , B2M , PTH

Hemodialysis

Replaces filtration

Diffusive and convective losses

Intermittent and short duration – 12 hours vs 168

Cont’

Removes volume , electrolytes , water soluble wastes and ( slowly) middle molecules and P04

No metabolismNo secretionNo synthetic functionNo removal of protein bound wastes

Urea Kinetic Modeling

TAC , AUCKt/VURRPRUeKt/VSingle pool Kt/VDouble pool V

Area under the Curve

Weekly substance concentrations in routine HD

Time

Conc

entra

tion

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

First Study

National Cooperative Dialysis Study (NCDS) published 1982

150 patients from 8 US centers4 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

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 minimumHigh TAC , 3 ½ hour group received Kt/V of

0.4 !

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

HEMO Trial 2002

? Optimal dialysis dose1846 patients Standard vs high dialysis dose and low vs

high flux dialyzersStandard dose group - Kt/V = 1.25High dose group - Kt/V = 1.65

Hemo outcomes

Outcome

17% mortality rate per year40% due to cardiac events

NO difference between any groups !

Risk of Death vs URR or Alb

URR

Albumin

Kt/V

K= dialyzer clearance

t = time on dialysis

V = volume of patient body water

? Calculate KT/V

Need pre/post urea

Existing patient data

Treatment info

All done same day

Need computer program

Urea Reduction Ratio (URR)

(Pre Urea – Post Urea ) /Pre Urea

A single snapshot , easy to calculate

PRU = URR x 100%

Prescribed vs Actual

Prescribed - computerized estimation

Actual – real run….. access that day , blood flow rates , treatment

time

Timing

When to measure post urea ?Too soon – post too low

Single pool RecirculationCompartment dysequilibrium

Timing of Post Urea

Dialyzers

Urea removed in relation to dialyzer surface area

Larger surface area = greater removal urea

Appropriate heparin to prevent clotting

No reuse

Other factors

Actual time on run

Access type ? Recirculation

Blood flow and dialysate flow rates – real vs entered

Episodes hypotension…..

KDOQI guidelines 2006

Three runs a weekMinimum run time 3 hours

Kt?/V - target 1.4 with min 1.2URR -target 70% with min 65%

Kt/V is standard of practice

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 !

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 !

Questions ?