KDIGO Controversies Conference Novel techniques and innovation in blood purification: How can we improve clinical outcomes in hemodialysis? October 14-15, 2011 Paris France Monitoring the Hemodialysis Dose Tom Depner, M.D. University of California, Davis
Slide 2 2001 By Default! Removal of accumulated small solutes is important A Free sample background from www.pptbackgrounds.fsnet.co.uk
How long will I live if I choose to stop dialysis? This varies from person to person. People who stop dialysis may live anywhere from one week to several weeks, depending on the amount of kidney function they have left and their overall medical condition. National Kidney Foundation web site
Art Buchwald Famous as a syndicated humorist in life, after his death he is more notable for his reputation as the man who beat hospice and the kidney machine.
How long will I live if I choose to stop dialysis? The median time to death after stopping dialysis in a series of 18 patients reported by Rich was 7 days (0-17 days) Rich A, Palliative Med 15:513-14, 2001.
The cause of death is uremia Principal cause: accumulation of toxic solutes normally excreted by the kidney Evidence: dialysis works by removing small solutes. Death is not due to anemia, vitamin D deficiency, hyperparathyroidism, fluid overload, accumulation of beta 2- microglobulin, etc, etc.
Minimum urea clearance for Hemodialysis KDOQI guidelines call for a continuous equivalent Kt/V urea of 2.0 volumes/week. 2.0 volumes per week x 35 L = 70 L/week = 70,000 ml/l /10080 min/week = 7 ml/min
Slide 8 HEMO Study: Survival by Kt/V Group 2001 By Default! A Free sample background from www.pptbackgrounds.fsnet.co.uk Eknoyan et al, N Eng J Med 2002
Weekly Dialysis Dose (stdkt/v) 7 6 5 4 3 2 1 Effect of Increasing Number of Dialysis Sessions Per Week Daily Dialysis HEMO: Standard 0 0.0 0.5 1.0 1.5 Dialysis dose each dialysis (ekt/v) 6 3 Hemodialysis sessions/wk HEMO: High 7 ml/min 8 ml/min 9
Slide 10 Deficiencies of Kt/V Residual kidney function not considered Solute disequilibrium is under-represented No provision for dialysis frequency K and t may not be equivalent V is independently associated with outcome Non-linear correlation with outcome
Effect of K r -urea on mortality in HD patients Termorshuizen F, et al: JASN 15:1061-70, 2004 RR mortality 20 18 16 14 12 10 8 6 5.0 to 62.6 Adjustments: age, comorbidity score, primary kidney disease, SGA, BMI 4 1.1 to 2.6 reference 2 0 0 0 to 0.84 >0.84 K r T/V per week
Slide 12 Deficiencies of Kt/V Residual kidney function not considered Solute disequilibrium is under-represented No provision for dialysis frequency K and t may not be equivalent V is independently associated with outcome Non-linear correlation with outcome
Slide 15 Standard K (and Kt/V) - Gotch Standard K = continuous removal rate average peak concentration In a steady state, the removal rate is equal to the generation rate (G) Standard K = G average peak concentration
Slide 16 2001 By Default! Standard Kt/V 10080 stdkt/v = 1 e ekt/v ekt/v 1 e ekt/v t 10080 + Nt 1 A Free sample background from www.pptbackgrounds.fsnet.co.uk Gotch, FA: Nephrol Dial Transplant 13 Suppl 6:10-14, 1998 Leypoldt, JK: Seminars In Dialysis 17:142-145, 2004
Slide 17 2001 By Default! Standard Kt/V adjusted for Uf and Kru stdkt/v = S/[1 - (0.74/F) Uf/V] + Kru [0.974/(spKt/V + 1.62) + 0.4] 10/V S is the unadjusted stdkt/v per week F is the number of dialyses/week Uf is the weekly fluid removal in liters Kru is the residual native kidney clearance of urea in ml/min spkt/v is the single pool Kt/V per dialysis V is the urea distribution volume in liters A Free sample background from www.pptbackgrounds.fsnet.co.uk Daugirdas J, et al: Kidney Int 2010
Standard Kt/V per week Continuous vs. intermittent clearance expressions 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0.0 0.00 0.50 1.00 1.50 2.00 2.50 spkt/v per dialysis 7/week 6 5 4 3 2 1
Slide 19 Re-defined Kt/V (per week) 7.0 6.0 5.0 4.0 2001 By Default! Continuous versus peak concentration methods 3.0 2.0 1.0 A Free sample background from www.pptbackgrounds.fsnet.co.uk Mean method Peak method 0.0 0.00 0.50 1.00 1.50 2.00 2.50 spkt/v per dialysis 7/week 6 5 4 3 2 1
Slide 20 Deficiencies of Kt/V Residual kidney function not considered Solute disequilibrium is under-represented No provision for dialysis frequency K and t may not be equivalent V is independently associated with outcome Non-linear correlation with outcome
Slide 21 1.20 Effect of treatment time on ekt/v spkt/v 2001 By Default! Kt/V 1.10 1.00 0.90 0.80 0.70 0.60 1.09 0.87 ekt/v A Free sample background from www.pptbackgrounds.fsnet.co.uk 2 4 6 8 10 T d (treatment time in hours)
Treatment time predicts mortality Saran et al from DOPPS, Kid Int 69:1222-28, 2006 New NKF-KDOQI Hemodialysis Guidelines
Slide 23 Relative Risk of death adjusted for age, sex, race & other factors 1.40 1.20 1.00 0.80 Mortality and Body Mass Index USRDS: 3607 patients enrolled in CMAS, Jan 1991 Source: Leavey et al, AJKD 31:1002, 1998 A Free sample background from www.pptbackgrounds.fsnet.co.uk quintile means ñ 95% confidence intervals 15 20 25 30 35 40 45 BMI 2001 By Default!
Slide 24 2001 By Default! K urea t urea V urea A Free sample background from www.pptbackgrounds.fsnet.co.uk
Slide 25 2001 By Default! 43,334 patients Continuous risk (hazard) plane for Kt and BSA. The analysis did not include an interaction term between Kt and BSA and was case mix adjusted. Continuous risk (hazard) plane for Kt and BSA. The analysis included an interaction term between Kt and BMI and was case mix adjusted. Lowrie E, et al: KI 62:1891-7, 2002 A Free sample background from www.pptbackgrounds.fsnet.co.uk
Slide 26 Deficiencies of Kt/V Residual kidney function not considered Solute disequilibrium is under-represented No provision for dialysis frequency K and t may not be equivalent V is independently associated with outcome Non-linear correlation with outcome
Concentration (Dose) - Response Curve Hill equation: applies to a direct reversible effect 1.0 Response (R) 0.8 0.6 0.4 0.2 R = C S (1/Q) + C S 0.0 0.5 1.0 10.0 Concentration (C in arbitrary units)
Concentration versus Clearance 10.0 8.0 6.0 C = 1/K 4.0 2.0 0.0 0.0 0.2 0.4 0.6 0.8 1.0 Clearance (K) in arbitrary units) Concentration (C in arbitrary units)
5 4.5 4 3.5 3 2.5 2 1.5 1 0.5 0 0 5 10 15 20 Steady-state solute concentration
Some proposed improvements to Kt/V Include residual native kidney clearance (Kr) Account for solute disequilibrium» ekt/v Allow for more frequent dialysis» Standardized Kt/V Index to surface area instead of V Tighter correlation with outcome» reciprocal of Kt/V
Slide 31 Summary: uremia is a complex state 2001 By Default! Comorbidity (DM, CVD, nutrition, anemia, etc) Residual Syndrome: Slowly accumulating solutes: B2-microglobulin & other peptides Calcium & phosphate deposits Protein-bound toxins? AGE s? Carbamylated proteins? Toxic effect of dialysis - exposure to membrane, hemodynamic effects A Free sample background from www.pptbackgrounds.fsnet.co.uk Life threatening toxins
Slide 32 2001 By Default! Future of dose monitoring Because control of small solute concentrations must be the principal goal of replacement therapy, future efforts should focus not on whether we should measure small solute clearance, but what else we should measure and do for our patients. A Free sample background from www.pptbackgrounds.fsnet.co.uk
Adequacy of Dialysis = Removal of Toxins = Prevention of Uremia = Restoration of Health