Renal replacement therapy with high-cutoff hemofilters: Impact of convection and diffusion on cytokine clearances and protein status.
BACKGROUND
High-cutoff hemofilters are characterized by an increased effective pore size designed to facilitate the elimination of inflammatory mediators in sepsis. This study compares diffusive versus convective high-cutoff renal replacement therapy (RRT) in terms of cytokine clearance rates and effects on plasma protein levels.


METHODS
Twenty-four patients with sepsis-induced acute renal failure were studied. A polyflux hemofilter with a cutoff point of approximately 60 kd was used for RRT. Patients were randomly allocated to either continuous venovenous hemofiltration (CVVH) with an ultrafiltration rate of 1 L/h (group 1) or 2.5 L/h (group 2) or continuous venovenous hemodialysis (CVVHD) with a dialysate flow rate of 1 L/h (group 3) or 2.5 L/h (group 4). Interleukin-1 (IL-1) receptor antagonist (IL-1ra), IL-1beta, IL-6, tumor necrosis factor-alpha (TNF-alpha), and plasma proteins were measured daily.


RESULTS
CVVH achieved significantly greater IL-1ra clearance compared with CVVHD (P = 0.0003). No difference was found for IL-6 (P = 0.935). Increasing ultrafiltration volume or dialysate flow led to a highly significant increase in IL-1ra and IL-6 clearance rates (P < 0.00001). Peak clearances were 46 mL/min for IL-1ra and 51 mL/min for IL-6. TNF-alpha clearance was poor for both RRT modalities. A significant decline in plasma IL-1ra and IL-6 clearance was observed in patients with high baseline levels. Protein and albumin losses were greatest during the 2.5-L/h hemofiltration mode.


CONCLUSIONS
High-cutoff RRT is a novel strategy to clear cytokines more effectively. Convection has an advantage over diffusion in the clearance capacity of IL-1ra, but is associated with greater plasma protein losses.
Morgera
Stanislao
S
Department of Nephrology, Charité, Humboldt University of Berlin, Germany. stanislao.morgera@charite.de
Slowinski
Torsten
T
Melzer
Christoph
C
Sobottke
Vanessa
V
Vargas-Hein
Ortrud
O
Volk
Thomas
T
Zuckermann-Becker
Heidrun
H
Wegner
Brigitte
B
Müller
Joachim M
JM
Baumann
Gerd
G
Kox
Wolfgang J
WJ
Bellomo
Rinaldo
R
Neumayer
Hans-H
HH
D000328:Adult; D000368:Aged; D001798:Blood Proteins; D016207:Cytokines / Q000097:blood; D005260:Female; D006440:Hemofiltration / Q000295:instrumentation; D006801:Humans; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000276:immunology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D012772:Shock, Septic / Q000150:complications
D001798:Blood Proteins; D016207:Cytokines