Membrane dialitiche emergenti: prospettive nel paziente acuto Elena Mancini Nefrologia, Dialisi, Ipertensione Policlinico S.Orsola-Malpighi Bologna - ITALY Corso di Aggiornamento “Acute kidney Injury: attualità e controversie” Roma, 19-20 maggio 2011
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Membrane dialitiche emergenti: prospettive nel paziente acuto
Vit E-coated membranes 8 RDT pts; 2 acute HD study sessions: Biocompatible vs VitE coated membranes
Vit E-coated
WHY NOT IN THE AKI PATIENT?
Improving efficiency
High / very high –MW solute
Protein-bound solutes
Superflux dialyzers (high cut off, protein leaking membranes)
Adsorbing membranes
Learning from RDT for the chronic patient
∅ < 0,01 µm ∅ < 0,02 µm
∅ ~ 0,09 µm
∅ ~ 0,30 µm
∅: pore diameter
high flux high cut-off*
protein separation membrane
plasma separation membrane
Electron micrographs of inner membrane surface
Variation of membrane pore size
High Cut-Off membrane
Cut-off ≈ 40.000 Dalton
Increase in: pore size homogeneous pore distribution ↓ Increase in membrane permeability Transfer of protein-bound solutes
Performance of HD membranes and protein permeability
Water permeability
(a) (ml/h/
mmHg/)
Beta2MG clearance (ml/min)
(b)
Albumin loss (grams)
(c)
Sieving Coeff
Beta2MG
Sieving Coeff
Albumin
Low-flux <6 <10 0 --- 0
High flux 20-40 20-40 <0.5 0.7-0.8 <0.001
Protein-leaking
40 >80 2.6 0.9-1.0 0.01-0.03
a) in vitro;
b) includes removal by diffusion, convection, adsorption
c) for 4h conventional HD Ward RA, JASN 2005
Superflux dialyzers on homocysteine levels (270 D, 75% protein-bound)
-20
-15
-10
-5
0
5
10
Superflux
Highflux Lowflux
43 pts, 4 weeks HD, tHcy, % change
De Vriese An S. et al. NDT 2003
*P<0.001
*
Time/weeks
Tota
l hom
ocys
tein
e, µ
mol
/L 45
35 25 15 5
1 12
10 pts, 12 weeks HD, tHcy, abs values
Van Tellingen A. et al. Kidney Int 2001
Superflux
Van Tellingen A et al NDT 2004
25 20 15 10 5 0 -5 -10 -15 -20 -25
Plasma leptin (ng/ml)
Week 1 week 12 week 1 week 12 week 1 week 12 week 1 week 12 F 6HPS TRIC EA 15 G F 60S F 500S
Superflux dialyzers on leptin levels
Superflux F500S
MW 160000 D 12 week observation period
Rhabdomyolysis and renal tubular casts
Glomeruli filtered myoglobin
Water adsorption, myoglobin concentration
Myoglobin, cast foramtion
Myoglobina, MW 16.700 D
Serum myoglobin trend using super high-flux (SHF)
continuos venos-venous hemofiltration (CVVH)
Naka T.
Critical Care 2005
High cutoff dialyzers in rhabdomyolysis
High cutoff hemofiltration in sepsis
Morgera S et al. Pilot study on the effects of high cutoff hemofiltration on the need for norepinephrine in septic patients with acute renal failure 34(8), 2006, 2099-2104
Morgera (Berlin), Joannidis (Innsbruck), Risler (Tübingen), Max (Marburg), Schindler (Berlin)
Multicenter study with septeX / HCO in septic AKI
HICOSS (High cut-off sepsis study)
Clark W. 10th Congress of WFSICCM, Florence 2009
Prospective, Randomized, Double-blinded Multicenter study
AKI after SIRS/Septic shock, requiring catecholamines
Primary outcome: 50% reduction of catecholamine requirements by High Cut off-CVVHD Secondary objectives: clinical improvements and safety (albumin levels), SOFA
120 pts
HCO (1.1 m2) Polyamide (1.1 m2)
CVVHD 5 days
CVVHD 5 days
Randomisation
QB 150-200 ml/min
QD 35 ml/Kg/h
QB 150-200 ml/min
QD 35 ml/Kg/h
● Days on Norephrinine (10,0 ±9 vs 11,3 ±9)
● Days on Ventilation (13,9 ±11 vs
16,1 ±11) ● Need for RRT (9,1 ±8 vs 9,5 ±8) ● days in ICU (19±12 vs 19±11)
HCO versus standard high flux
N= 81 pts CVVHD
Membrane A
Membrane B
Membrane A
Membrane BHigh-Flux HCO
Clark W. 10th Congress of WFSICCM, Florence 2009
HICOSS Study results
High cut off dialyzers: not only cytokines
Inflammatory mediators, Beta-2MG, Myoglobulin & light chains: similar MW
κ chain ≅ 22000 daltons λ chain ≅ 44000 daltons
HCO1100 for light chain removal: Malpighi (Bologna) experience