hemodialysis vs. hemodiafiltration

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Hemodialysis vs. Hemodiafiltration. Hemodialysis Symposium 8-9 February, 2014 Al- Madinah Al- Munawwarah , KSA Saad Alobaili KKUH, KSU Riyadh. Main Uremic Toxins. 3 Mechanisms of solute removal. - PowerPoint PPT Presentation

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Online HDF

Hemodialysis vs. Hemodiafiltration Hemodialysis Symposium8-9 February, 2014Al-Madinah Al-Munawwarah, KSA

Saad AlobailiKKUH, KSURiyadhClassificationMolecular weight rangeSmall moleculese.g. urea (60), creatinine (113), phosphate (134)< 500 Middle moleculese.g. vitamin B12 (1355), vancomycin (1448), inulin *5200, endotoxin fragments (1000-15,000) parathormone (9425), 2-m (11,818)500 15,000Large moleculese.g. myoglobulin (17,000), RBP (21,000), 1-m (26,700), EPO (30,000), albumin (66,000), transferrin (90,000)

> 15,000Main Uremic Toxins

3 Mechanisms of solute removal1- Diffusion: Solute removal according to concentration difference between plasma water and the dialysate. Is greatest for small molecules removalSmall molecules have better access to the membrane Increase with increasing the small solute conce. gradientMembrane factors: Sieving coefficient, porosity of the membrane, diffusivity & thickness of the membraneDecreases with increasing molecular size of a solute

Basic Principles of solute removal2- Convection: solute clearance occurs as a result of water flow through the membrane in response to hydrostatic pressure difference between the two sides of the membrane.(solvent drag).The driving force is a pressure gradient rather than a concentration gradientThe major impact comes from the solute size relative to the membrane pores size (radius)Iis determined exclusively by the sieving properties of the membrane, S=1 for WaterIs more important for solute removal as the molecular size of the solute increases.Serves 2 purposes: water and solute removal along.

Basic Principles of solute removal3- Adsorption: Plasma proteins being adsorbed to the surface of the membrane. ( So, effect is limited to LMW Proteins clearance)Difficult t estimateHigh flux membranes has more protein adsorption than Low Flux membranes ( Larger pores) Ay decrease the Diffusive & Convective transport of LMW proteins.

I. Ledebo and P. J. Blankestijn, NDT plus 2010Determinants of Convective Transport Across Membranes:Water flux across the membrane Pore size and pore size distribution of the membrane Molecular size (molecular mass)Hydrostatic pressure difference Viscosity of the fluid in the membrane pores Molecular shape and configurationCharges (solutes and membranes)

Important Dialyzer character relevant to its Convective function: Ucoeff or KUF: ( mL/h/mm Hg)It characterizes the membranes permeability to water.The higher Ucoeff is, the greater the permeability to waterThe higher Ucoeff is, the greater contribution of CONVECTION (solvent drag) to solute removal (middle molecules)

Dialyzers are classified as: Ucoeff (ml/h/mm Hg)2-Microglobulin Clearance ( mL/min)Conventional 12 10 High-flux > 14 ( > 40 ) >20 - Some refer to FLUX as ability to remove 2-M.- High-Flux dialyzers: are considered convective dialyzers ( Filtration and back filtration of 6-8 L over 4 hs conventional HD session.

Ledebo I. Principles and practice of hemofiltration and hemodiafiltration.Artif Organs 1998; 22: 2025Both the Hemodialysis (HEMO) study and the Membrane Permeability Outcome (MPO) study compared low-fl ux hemodialysis with high-fl ux hemodialysis. Neither study showed a difference in mortality risk between the treatment arms.In HEMO, High-flux HD was associated with an 8% non-significant reduction of mortality compared with low-flux HDSecondary analyses in the HEMO and MPO studies suggested a survival benefit of high-flux hemodialysis in patients with a dialysis vintage >3.7 years, patients with diabetes, and if serum albumin < 40 g/L at baseline.

Uremic solutes with known negative impact on the cell systems involved in atherogenesis and the clinical development of cardiovascular and cerebrovascular problems, CV mortality rate is still 10 times higher than in thegeneral populationJ Am Soc Nephrol 9[Suppl]: S16S23, 1998

Vanholder et alThe International Journal of Artificial Organs / Vol. 24 / no. 10, 2001 Normal 2 microglobulin level: 1-2 mg/L

Targeted in HD population 15-20 mg/L

RISCAVIDProspective study of 757 HD patients, followed for 30 monthsHD (n = 424)Haemodiafiltration with sterile bags (n = 204)online HDF (n = 129)

RISCAVIDAll-cause and CV mortality was 12.9%/year(HD) and 5.9%/year(HDF)CRP and pro-inflammatory cytokines showed an increased risk for CV (RR 1.9, P < 0.001) and all-cause mortality (RR 2.57, P < 0.001)HDF patients had a significantly increased adjusted cumulative survival than BHD (P < 0.01)Conventional HD= Diffusion + convection (UF) for excess fluid removal + convective clearance LMW (if high flux)

If Convective clearance is augmented (large convective volume applied) for the sake of improving LMW proteins clearance: Diffusion + Convection ( LMW P. removal) + UF (excess fluid removal) = Hemodiafiltration (HDF) HDF is a blood purification therapy combing diffusive and convective solute transport using high -flux membranes characterized by an ultrafiltration coefficient > 20 ml/h/mm Hg/m and a sieving coefficient for 2- microglobulin greater than 0.6 Convective transport is achieved by an effective convection volume of at least 20 % of the total blood volume processed. Appropriate fluid balance is maintained by external infusion of an ultrapure, non -pyrogenic solution into the patient`s blood.

Hemodiafiltration; beside the ongoing diffusive therapy in the HD part, it relies on a large convective volume requiring substitution fluid equal to the convicted volume.

(e.g. 15 Ls to be convicted over 4hs in an HDF session then it has to be replaced simultaneously with another 15 Ls of Ultra-pure water based substitution solution) Advantages of HDF:Enhanced small, middle and larger m removalProtein-bound uremic solute clearanceBetter intradialytic hemodynamic stability Reduced inflammation & infectionAnemia correction Improved phosphate controlImproved CV status

Reduction ratio of B2M per session was 2030% higher with on-line HDF than with high-flux HD (72.7 versus 49.7%) Nephrol Dial Transplant 2000; 15(Suppl 1)

Carpal tunnel syndrome surgery: 42% lower in patients treated with HDF compared with those treated with HD Kidney Int 1999; 55: 286293

On-line HDF permits a similar reduction rate of small solutes per session as that of HD: 7080% for urea (60 daltons (da)Nephrol Dial Transplant 2005; 20: 155160The substitution Fluid source:

1- Sterile fluid in pre-filed bags from a manufacturer.OR2- On site prepared solution ( same as dialysate) (water from the RO further treated inside the HDF machine)Hence called On-Line HDF.Substitution Fluid Preparation steps:

ANSI /AAMI/ ISO ERA-EDTA guidelinesWater for dialysisBacteria (CFU/ml)