Hemodialysis Membrane With a High-Molecular-Weight Cutoff and Cytokine Levels in Sepsis Complicated by Acute Renal Failure: A Phase 1 Randomized Trial

Michael Haase, Rinaldo Bellomo, Ian Baldwin, Anja Haase-Fielitz, Nigel Fealy, Piers Davenport, Stanislao Morgera, Hermann Goehl, Markus Storr, Neil Boyce, Hans Hellmut Neumayer

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Abstract

Background: Sepsis is the leading cause of acute renal failure. Intermittent hemodialysis (IHD) is a common treatment for patients with acute renal failure. However, standard hemodialysis membranes achieve only little diffusive removal of circulating cytokines. Modified membranes may enable both successful IHD treatment and simultaneous diffusive cytokine removal. Study Design: Double-blind, crossover, randomized, controlled, phase 1 trial. Setting & Participants: Tertiary intensive care unit. 10 septic patients with acute renal failure according to RIFLE class F. Intervention: Each patient was treated with 4 hours of high-cutoff (HCO)-IHD and 4 hours of high-flux (HF)-IHD. Outcomes & Measurements: We chose relative change in plasma interleukin 6 (IL-6) concentrations from baseline to 4 hours as the primary outcome for effective cytokine removal. We measured plasma and effluent concentrations of cytokines (IL-6, IL-8, IL-10, and IL-18) and albumin. Results: Median age was 53 years (25th to 75th percentiles, 43 to 71 years). Both treatments achieved equal control of uremia. Four hours of HCO-IHD accomplished a greater decrease in plasma IL-6 levels (-30.3%) than 4 hours of HF-IHD (1.1%; P = 0.05). HCO-IHD, but not HF-IHD, achieved substantial diffusive clearance of several cytokines (IL-6, 14.1 mL/min; IL-8, 75.2 mL/min; and IL-10, 25.5 mL/min). Such clearance also was associated with greater relative decreases in plasma IL-8 and IL-10 levels in favor of HCO-IHD (P = 0.02, P = 0.04). We found significantly greater relative changes from prefilter to postfilter plasma IL-6, IL-8, and IL-10 values in favor of HCO-IHD (P = 0.02, P = 0.01, P < 0.01). During HCO-IHD, cumulative albumin loss into the effluent was 7.7 g (25th to 75th percentiles, 4.8 to 19.6) versus less than 1.0 g for HF-IHD (P < 0.01). Limitations: Small phase 1 trial. Conclusion: In septic patients with acute renal failure, HCO-IHD achieved simultaneous uremic control and diffusive cytokine clearances and a greater relative decrease in plasma cytokine concentrations than standard HF-IHD.

Original languageEnglish
Pages (from-to)296-304
Number of pages9
JournalAmerican Journal of Kidney Diseases
Volume50
Issue number2
DOIs
Publication statusPublished - 1 Aug 2007
Externally publishedYes

Keywords

  • acute renal failure
  • cytokines
  • high-cutoff-point membranes
  • intermittent hemodialysis
  • polyamide
  • Sepsis

Cite this

Haase, Michael ; Bellomo, Rinaldo ; Baldwin, Ian ; Haase-Fielitz, Anja ; Fealy, Nigel ; Davenport, Piers ; Morgera, Stanislao ; Goehl, Hermann ; Storr, Markus ; Boyce, Neil ; Neumayer, Hans Hellmut. / Hemodialysis Membrane With a High-Molecular-Weight Cutoff and Cytokine Levels in Sepsis Complicated by Acute Renal Failure : A Phase 1 Randomized Trial. In: American Journal of Kidney Diseases. 2007 ; Vol. 50, No. 2. pp. 296-304.
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abstract = "Background: Sepsis is the leading cause of acute renal failure. Intermittent hemodialysis (IHD) is a common treatment for patients with acute renal failure. However, standard hemodialysis membranes achieve only little diffusive removal of circulating cytokines. Modified membranes may enable both successful IHD treatment and simultaneous diffusive cytokine removal. Study Design: Double-blind, crossover, randomized, controlled, phase 1 trial. Setting & Participants: Tertiary intensive care unit. 10 septic patients with acute renal failure according to RIFLE class F. Intervention: Each patient was treated with 4 hours of high-cutoff (HCO)-IHD and 4 hours of high-flux (HF)-IHD. Outcomes & Measurements: We chose relative change in plasma interleukin 6 (IL-6) concentrations from baseline to 4 hours as the primary outcome for effective cytokine removal. We measured plasma and effluent concentrations of cytokines (IL-6, IL-8, IL-10, and IL-18) and albumin. Results: Median age was 53 years (25th to 75th percentiles, 43 to 71 years). Both treatments achieved equal control of uremia. Four hours of HCO-IHD accomplished a greater decrease in plasma IL-6 levels (-30.3{\%}) than 4 hours of HF-IHD (1.1{\%}; P = 0.05). HCO-IHD, but not HF-IHD, achieved substantial diffusive clearance of several cytokines (IL-6, 14.1 mL/min; IL-8, 75.2 mL/min; and IL-10, 25.5 mL/min). Such clearance also was associated with greater relative decreases in plasma IL-8 and IL-10 levels in favor of HCO-IHD (P = 0.02, P = 0.04). We found significantly greater relative changes from prefilter to postfilter plasma IL-6, IL-8, and IL-10 values in favor of HCO-IHD (P = 0.02, P = 0.01, P < 0.01). During HCO-IHD, cumulative albumin loss into the effluent was 7.7 g (25th to 75th percentiles, 4.8 to 19.6) versus less than 1.0 g for HF-IHD (P < 0.01). Limitations: Small phase 1 trial. Conclusion: In septic patients with acute renal failure, HCO-IHD achieved simultaneous uremic control and diffusive cytokine clearances and a greater relative decrease in plasma cytokine concentrations than standard HF-IHD.",
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author = "Michael Haase and Rinaldo Bellomo and Ian Baldwin and Anja Haase-Fielitz and Nigel Fealy and Piers Davenport and Stanislao Morgera and Hermann Goehl and Markus Storr and Neil Boyce and Neumayer, {Hans Hellmut}",
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Haase, M, Bellomo, R, Baldwin, I, Haase-Fielitz, A, Fealy, N, Davenport, P, Morgera, S, Goehl, H, Storr, M, Boyce, N & Neumayer, HH 2007, 'Hemodialysis Membrane With a High-Molecular-Weight Cutoff and Cytokine Levels in Sepsis Complicated by Acute Renal Failure: A Phase 1 Randomized Trial', American Journal of Kidney Diseases, vol. 50, no. 2, pp. 296-304. https://doi.org/10.1053/j.ajkd.2007.05.003

Hemodialysis Membrane With a High-Molecular-Weight Cutoff and Cytokine Levels in Sepsis Complicated by Acute Renal Failure : A Phase 1 Randomized Trial. / Haase, Michael; Bellomo, Rinaldo; Baldwin, Ian; Haase-Fielitz, Anja; Fealy, Nigel; Davenport, Piers; Morgera, Stanislao; Goehl, Hermann; Storr, Markus; Boyce, Neil; Neumayer, Hans Hellmut.

In: American Journal of Kidney Diseases, Vol. 50, No. 2, 01.08.2007, p. 296-304.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Hemodialysis Membrane With a High-Molecular-Weight Cutoff and Cytokine Levels in Sepsis Complicated by Acute Renal Failure

T2 - A Phase 1 Randomized Trial

AU - Haase, Michael

AU - Bellomo, Rinaldo

AU - Baldwin, Ian

AU - Haase-Fielitz, Anja

AU - Fealy, Nigel

AU - Davenport, Piers

AU - Morgera, Stanislao

AU - Goehl, Hermann

AU - Storr, Markus

AU - Boyce, Neil

AU - Neumayer, Hans Hellmut

PY - 2007/8/1

Y1 - 2007/8/1

N2 - Background: Sepsis is the leading cause of acute renal failure. Intermittent hemodialysis (IHD) is a common treatment for patients with acute renal failure. However, standard hemodialysis membranes achieve only little diffusive removal of circulating cytokines. Modified membranes may enable both successful IHD treatment and simultaneous diffusive cytokine removal. Study Design: Double-blind, crossover, randomized, controlled, phase 1 trial. Setting & Participants: Tertiary intensive care unit. 10 septic patients with acute renal failure according to RIFLE class F. Intervention: Each patient was treated with 4 hours of high-cutoff (HCO)-IHD and 4 hours of high-flux (HF)-IHD. Outcomes & Measurements: We chose relative change in plasma interleukin 6 (IL-6) concentrations from baseline to 4 hours as the primary outcome for effective cytokine removal. We measured plasma and effluent concentrations of cytokines (IL-6, IL-8, IL-10, and IL-18) and albumin. Results: Median age was 53 years (25th to 75th percentiles, 43 to 71 years). Both treatments achieved equal control of uremia. Four hours of HCO-IHD accomplished a greater decrease in plasma IL-6 levels (-30.3%) than 4 hours of HF-IHD (1.1%; P = 0.05). HCO-IHD, but not HF-IHD, achieved substantial diffusive clearance of several cytokines (IL-6, 14.1 mL/min; IL-8, 75.2 mL/min; and IL-10, 25.5 mL/min). Such clearance also was associated with greater relative decreases in plasma IL-8 and IL-10 levels in favor of HCO-IHD (P = 0.02, P = 0.04). We found significantly greater relative changes from prefilter to postfilter plasma IL-6, IL-8, and IL-10 values in favor of HCO-IHD (P = 0.02, P = 0.01, P < 0.01). During HCO-IHD, cumulative albumin loss into the effluent was 7.7 g (25th to 75th percentiles, 4.8 to 19.6) versus less than 1.0 g for HF-IHD (P < 0.01). Limitations: Small phase 1 trial. Conclusion: In septic patients with acute renal failure, HCO-IHD achieved simultaneous uremic control and diffusive cytokine clearances and a greater relative decrease in plasma cytokine concentrations than standard HF-IHD.

AB - Background: Sepsis is the leading cause of acute renal failure. Intermittent hemodialysis (IHD) is a common treatment for patients with acute renal failure. However, standard hemodialysis membranes achieve only little diffusive removal of circulating cytokines. Modified membranes may enable both successful IHD treatment and simultaneous diffusive cytokine removal. Study Design: Double-blind, crossover, randomized, controlled, phase 1 trial. Setting & Participants: Tertiary intensive care unit. 10 septic patients with acute renal failure according to RIFLE class F. Intervention: Each patient was treated with 4 hours of high-cutoff (HCO)-IHD and 4 hours of high-flux (HF)-IHD. Outcomes & Measurements: We chose relative change in plasma interleukin 6 (IL-6) concentrations from baseline to 4 hours as the primary outcome for effective cytokine removal. We measured plasma and effluent concentrations of cytokines (IL-6, IL-8, IL-10, and IL-18) and albumin. Results: Median age was 53 years (25th to 75th percentiles, 43 to 71 years). Both treatments achieved equal control of uremia. Four hours of HCO-IHD accomplished a greater decrease in plasma IL-6 levels (-30.3%) than 4 hours of HF-IHD (1.1%; P = 0.05). HCO-IHD, but not HF-IHD, achieved substantial diffusive clearance of several cytokines (IL-6, 14.1 mL/min; IL-8, 75.2 mL/min; and IL-10, 25.5 mL/min). Such clearance also was associated with greater relative decreases in plasma IL-8 and IL-10 levels in favor of HCO-IHD (P = 0.02, P = 0.04). We found significantly greater relative changes from prefilter to postfilter plasma IL-6, IL-8, and IL-10 values in favor of HCO-IHD (P = 0.02, P = 0.01, P < 0.01). During HCO-IHD, cumulative albumin loss into the effluent was 7.7 g (25th to 75th percentiles, 4.8 to 19.6) versus less than 1.0 g for HF-IHD (P < 0.01). Limitations: Small phase 1 trial. Conclusion: In septic patients with acute renal failure, HCO-IHD achieved simultaneous uremic control and diffusive cytokine clearances and a greater relative decrease in plasma cytokine concentrations than standard HF-IHD.

KW - acute renal failure

KW - cytokines

KW - high-cutoff-point membranes

KW - intermittent hemodialysis

KW - polyamide

KW - Sepsis

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