Hemodialysis Adequacy: A Complex and Evolving Paradigm

35 Pages·2009·4.01 MB·English

Hemodialysis Adequacy:
A Complex and Evolving
Paradigm
Balazs Szamosfalvi, MD
Saturday, 08/29/2009 12:15-12:45
Adequacy 1943 - 1970
• The patient survived
the dialysis session
• Uremia improved
• Volume status
improved
• Patient survival to
©Fresenius ©Freserneiusc overy of kidney
function or transplant
Source: http://www.homedialysis.org/learn/museum/
Adequacy 1970 - 2000
• Safe dialysis sessions in
large numbers
• Good control of uremia
• Focus on small solute
(urea) kinetics
• Volumetric ultrafiltration
• Patient survival on
©Fresenius ©Fresenius
dialysis for years
• Large clinical studies and
guideline development
Source: http://www.homedialysis.org/learn/museum/
Adequacy 2000 – into the future
Computer-Aided HD
design and monitoring
(Online Clearance)
Reduced Inflammation: Middle Molecule Removal:
Better Biocompatibility Hemo-diafiltration and
and Ultrapure dialysate Internal Filtration
Daily and or long
Adequacy
(nocturnal) dialysis for
Blood volume
of Dialysis BP and Ca x P control
monitoring for safer
ultrafiltration
Increasing Focus on
Cost-control
OUTCOME:
Quality of life
Rehabilitation
Morbidity &
Mortality
HD Adequacy
1. Definition of uremic syndrome and toxins
(cid:131) Uremic toxin removal
(cid:131) Volume homeostasis
2. Kinetic studies of solute movement
(cid:131) Solute flux studies on the dialyzer
(cid:131) Online dialyzer flux measurements and computer modeling
(cid:131) Solute flux studies in the patient
(cid:131) Computer modeling of patient solute fluxes and levels
3. Large clinical studies
(cid:131) Validate kinetic analyses
(cid:131) Inform guideline development for best dialysis practices
(cid:131) Databases: Observational evaluation of novel therapies
(cid:131) Questionnaires: Incorporate “user acceptance” into guideline
development (e.g. forget 30 minute post-HD urea sampling)
Uremic toxins
I. Small (< 500 D); water soluble
(cid:131) Surrogate marker urea or sodium (ionic dialysance)
(cid:131) Rapidly produced in intracellular fluid compartment
(cid:131) Large variability in intra-patient kinetics (e.g. phosphate)
II. Middle-molecules (500 – 40,000 D); water soluble
(cid:131) Β2-microglobulin, PTH, some cytokines (IL-6, TNF)
(cid:131) Optimized filter design and convection for removal
(cid:131) Complex intra-patient kinetics (generation, compartments)
III. Small (< 500 D); protein-bound
(cid:131) Poorly removed with traditional dialysis
(cid:131) Resin adsorption-based therapies are in development
Vanholder et al:Review on uremic toxins; Kidney International, Vol. 63 (2003), pp. 1934–1943
Vanholder et al:A bench to bedside view of uremic toxins; J Am Soc Nephrol 19: 863–870, 2008.
European Uremic Toxin Work Group (Eutox; http://EUTox.info)
Examples of uremic toxins
From Primer On Kidney Diseases, 2nd editition
Solute fluxes on the dialyzer
1. Nomenclature
• Clearance and dialysance
• Efficiency and flux (membrane area and pore size)
• Diffusion and or convection (plus adsorption)
2. Analytical mathematical models and solutions
• Concept of K A and the classic diffusive clearance equation
0
• Limitations of K A: effect of internal filtration and shunting
0
• Bio-fouling: albumin coating, progressive clotting
3. Computer models and online measurements
• More precise modeling of mathematically complex treatments
• Online, multiple measurements of delivered ionic dialysance
(precise surrogate for effective urea clearance)
Depner T and Garred L: Solute transport mechanisms in dialysis; in Replacement of Renal
Function by Dialysis, 5th edition; p73-93
Nomenclature
1. Dialysance and Clearance
• The volume of blood cleared from the concentration difference
of a solute between the fresh blood and the fresh dialysis fluid
entering the filter
• Clearance: special case of dialysance when the fresh dialysate
solute concentration is zero
2. Efficiency and Flux
• Efficiency: ability to achieve large small solute clearance with
high blood flows (all filters are high efficiency these days)
• Flux: ability to achieve high middle molecule clearance and
ultrafiltration rate (determined by the average pore size)
3. Diffusion and Convection
• Diffusion: solutes move by diffusion between blocks of fluid
separated by the membrane
• Convection: solutes move en mass with a block of fluid across
the membrane (more effective for moving large molecules)
Membrane Flux and Pore Size 1
Sivasankaran Ambalavanan, Gary Rabetoy & Alfred K. Cheung; www.kidneyatlas.org