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 environment Continuous function and adjustment of metabolic parameters Filtration Secretion Metabolic Synthetic
Uremic Toxins Many known, many more unknown Small water soluble – urea Larger water soluble –guanidines Phosphates Protein 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 metabolism No secretion No synthetic function No removal of protein bound wastes
Urea Kinetic Modeling TAC, AUC Kt/V URR PRU eKt/V Single pool Kt/V Double pool V
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 centers 4 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 minimum High 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 dose 1846 patients Standard vs high dialysis dose and low vs high flux dialyzers Standard dose group - Kt/V = 1.25 High dose group - Kt/V = 1.65
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 week Minimum run time 3 hours Kt?/V - target 1.4 with min 1.2 URR -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 !