Plasma inflammatory and apoptosis markers are associated with dialysis dependence and death among critically ill patients receiving renal replacement therapy

Raghavan Murugan, Xiaoyan Wen, Nilesh Shah, Minjae Lee, Lan Kong, Francis Pike, Christopher Keener, Mark Unruh, Kevin Finkel, Anitha Vijayan, Paul M. Palevsky, Emil Paganini, Melinda Carter, Michele Elder, John A. Kellum

Research output: Contribution to journalArticle

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Abstract

Background Survivors of critical illness complicated by acute kidney injury requiring renal replacement therapy (RRT) are at an increased risk of dialysis dependence and death but the mechanisms are unknown. Methods In a multicenter, prospective, cohort study of 817 critically ill patients receiving RRT, we examined association between Day 1 plasma inflammatory [interleukin (IL)-1β, IL-6, IL-8, IL-10 and IL-18; macrophage migration inhibitory factor (MIF) and tumor necrosis factor]; apoptosis [tumor necrosis factor receptor (TNFR)-I and TNFR-II and death receptor (DR)-5]; and growth factor (granulocyte macrophage colony stimulating factor) biomarkers and renal recovery and mortality at Day 60. Renal recovery was defined as alive and RRT independent. Results Of 817 participants, 36.5% were RRT independent and 50.8% died. After adjusting for differences in demographics, comorbid conditions; premorbid creatinine; nephrotoxins; sepsis; oliguria; mechanical ventilation; RRT dosing; and severity of illness, increased concentrations of plasma IL-8 and IL-18 and TNFR-I were independently associated with slower renal recovery [adjusted hazard ratio (AHR) range for all markers, 0.70-0.87]. Higher concentrations of IL-6, IL-8, IL-10 and IL-18; MIF; TNFR-I and DR-5 were associated with mortality (AHR range, 1.16-1.47). In an analysis of multiple markers simultaneously, increased IL-8 [AHR, 0.80, 95% confidence interval (95% CI) 0.70-0.91, P < 0.001] and TNFR-I (AHR, 0.63, 95% CI 0.50-0.79, P < 0.001) were associated with slower recovery, and increased IL-8 (AHR, 1.26, 95% CI 1.14-1.39, P < 0.001); MIF (AHR, 1.18, 95% CI 1.08-1.28, P < 0.001) and TNFR-I (AHR, 1.26, 95% CI 1.02-1.56, P < 0.03) were associated with mortality. Conclusions Elevated plasma concentrations of inflammatory and apoptosis biomarkers are associated with RRT dependence and death. Our data suggest that future interventions should investigate broad-spectrum immune-modulation to improve outcomes.

Original languageEnglish (US)
Pages (from-to)1854-1864
Number of pages11
JournalNephrology Dialysis Transplantation
Volume29
Issue number10
DOIs
StatePublished - Oct 1 2014

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Renal Replacement Therapy
Tumor Necrosis Factor Receptors
Critical Illness
Dialysis
Interleukin-8
Interleukin-18
Confidence Intervals
TNF-Related Apoptosis-Inducing Ligand Receptors
Kidney
Interleukin-10
Mortality
Interleukin-6
Biomarkers
Macrophage Migration-Inhibitory Factors
Oliguria
Granulocyte-Macrophage Colony-Stimulating Factor
Interleukin-1
Artificial Respiration
Acute Kidney Injury
Survivors

All Science Journal Classification (ASJC) codes

  • Nephrology
  • Transplantation

Cite this

Murugan, Raghavan ; Wen, Xiaoyan ; Shah, Nilesh ; Lee, Minjae ; Kong, Lan ; Pike, Francis ; Keener, Christopher ; Unruh, Mark ; Finkel, Kevin ; Vijayan, Anitha ; Palevsky, Paul M. ; Paganini, Emil ; Carter, Melinda ; Elder, Michele ; Kellum, John A. / Plasma inflammatory and apoptosis markers are associated with dialysis dependence and death among critically ill patients receiving renal replacement therapy. In: Nephrology Dialysis Transplantation. 2014 ; Vol. 29, No. 10. pp. 1854-1864.
@article{6b8e1bcf81fa40e19a2a1c881a1c2900,
title = "Plasma inflammatory and apoptosis markers are associated with dialysis dependence and death among critically ill patients receiving renal replacement therapy",
abstract = "Background Survivors of critical illness complicated by acute kidney injury requiring renal replacement therapy (RRT) are at an increased risk of dialysis dependence and death but the mechanisms are unknown. Methods In a multicenter, prospective, cohort study of 817 critically ill patients receiving RRT, we examined association between Day 1 plasma inflammatory [interleukin (IL)-1β, IL-6, IL-8, IL-10 and IL-18; macrophage migration inhibitory factor (MIF) and tumor necrosis factor]; apoptosis [tumor necrosis factor receptor (TNFR)-I and TNFR-II and death receptor (DR)-5]; and growth factor (granulocyte macrophage colony stimulating factor) biomarkers and renal recovery and mortality at Day 60. Renal recovery was defined as alive and RRT independent. Results Of 817 participants, 36.5{\%} were RRT independent and 50.8{\%} died. After adjusting for differences in demographics, comorbid conditions; premorbid creatinine; nephrotoxins; sepsis; oliguria; mechanical ventilation; RRT dosing; and severity of illness, increased concentrations of plasma IL-8 and IL-18 and TNFR-I were independently associated with slower renal recovery [adjusted hazard ratio (AHR) range for all markers, 0.70-0.87]. Higher concentrations of IL-6, IL-8, IL-10 and IL-18; MIF; TNFR-I and DR-5 were associated with mortality (AHR range, 1.16-1.47). In an analysis of multiple markers simultaneously, increased IL-8 [AHR, 0.80, 95{\%} confidence interval (95{\%} CI) 0.70-0.91, P < 0.001] and TNFR-I (AHR, 0.63, 95{\%} CI 0.50-0.79, P < 0.001) were associated with slower recovery, and increased IL-8 (AHR, 1.26, 95{\%} CI 1.14-1.39, P < 0.001); MIF (AHR, 1.18, 95{\%} CI 1.08-1.28, P < 0.001) and TNFR-I (AHR, 1.26, 95{\%} CI 1.02-1.56, P < 0.03) were associated with mortality. Conclusions Elevated plasma concentrations of inflammatory and apoptosis biomarkers are associated with RRT dependence and death. Our data suggest that future interventions should investigate broad-spectrum immune-modulation to improve outcomes.",
author = "Raghavan Murugan and Xiaoyan Wen and Nilesh Shah and Minjae Lee and Lan Kong and Francis Pike and Christopher Keener and Mark Unruh and Kevin Finkel and Anitha Vijayan and Palevsky, {Paul M.} and Emil Paganini and Melinda Carter and Michele Elder and Kellum, {John A.}",
year = "2014",
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doi = "10.1093/ndt/gfu051",
language = "English (US)",
volume = "29",
pages = "1854--1864",
journal = "Nephrology Dialysis Transplantation",
issn = "0931-0509",
publisher = "Oxford University Press",
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}

Murugan, R, Wen, X, Shah, N, Lee, M, Kong, L, Pike, F, Keener, C, Unruh, M, Finkel, K, Vijayan, A, Palevsky, PM, Paganini, E, Carter, M, Elder, M & Kellum, JA 2014, 'Plasma inflammatory and apoptosis markers are associated with dialysis dependence and death among critically ill patients receiving renal replacement therapy', Nephrology Dialysis Transplantation, vol. 29, no. 10, pp. 1854-1864. https://doi.org/10.1093/ndt/gfu051

Plasma inflammatory and apoptosis markers are associated with dialysis dependence and death among critically ill patients receiving renal replacement therapy. / Murugan, Raghavan; Wen, Xiaoyan; Shah, Nilesh; Lee, Minjae; Kong, Lan; Pike, Francis; Keener, Christopher; Unruh, Mark; Finkel, Kevin; Vijayan, Anitha; Palevsky, Paul M.; Paganini, Emil; Carter, Melinda; Elder, Michele; Kellum, John A.

In: Nephrology Dialysis Transplantation, Vol. 29, No. 10, 01.10.2014, p. 1854-1864.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Plasma inflammatory and apoptosis markers are associated with dialysis dependence and death among critically ill patients receiving renal replacement therapy

AU - Murugan, Raghavan

AU - Wen, Xiaoyan

AU - Shah, Nilesh

AU - Lee, Minjae

AU - Kong, Lan

AU - Pike, Francis

AU - Keener, Christopher

AU - Unruh, Mark

AU - Finkel, Kevin

AU - Vijayan, Anitha

AU - Palevsky, Paul M.

AU - Paganini, Emil

AU - Carter, Melinda

AU - Elder, Michele

AU - Kellum, John A.

PY - 2014/10/1

Y1 - 2014/10/1

N2 - Background Survivors of critical illness complicated by acute kidney injury requiring renal replacement therapy (RRT) are at an increased risk of dialysis dependence and death but the mechanisms are unknown. Methods In a multicenter, prospective, cohort study of 817 critically ill patients receiving RRT, we examined association between Day 1 plasma inflammatory [interleukin (IL)-1β, IL-6, IL-8, IL-10 and IL-18; macrophage migration inhibitory factor (MIF) and tumor necrosis factor]; apoptosis [tumor necrosis factor receptor (TNFR)-I and TNFR-II and death receptor (DR)-5]; and growth factor (granulocyte macrophage colony stimulating factor) biomarkers and renal recovery and mortality at Day 60. Renal recovery was defined as alive and RRT independent. Results Of 817 participants, 36.5% were RRT independent and 50.8% died. After adjusting for differences in demographics, comorbid conditions; premorbid creatinine; nephrotoxins; sepsis; oliguria; mechanical ventilation; RRT dosing; and severity of illness, increased concentrations of plasma IL-8 and IL-18 and TNFR-I were independently associated with slower renal recovery [adjusted hazard ratio (AHR) range for all markers, 0.70-0.87]. Higher concentrations of IL-6, IL-8, IL-10 and IL-18; MIF; TNFR-I and DR-5 were associated with mortality (AHR range, 1.16-1.47). In an analysis of multiple markers simultaneously, increased IL-8 [AHR, 0.80, 95% confidence interval (95% CI) 0.70-0.91, P < 0.001] and TNFR-I (AHR, 0.63, 95% CI 0.50-0.79, P < 0.001) were associated with slower recovery, and increased IL-8 (AHR, 1.26, 95% CI 1.14-1.39, P < 0.001); MIF (AHR, 1.18, 95% CI 1.08-1.28, P < 0.001) and TNFR-I (AHR, 1.26, 95% CI 1.02-1.56, P < 0.03) were associated with mortality. Conclusions Elevated plasma concentrations of inflammatory and apoptosis biomarkers are associated with RRT dependence and death. Our data suggest that future interventions should investigate broad-spectrum immune-modulation to improve outcomes.

AB - Background Survivors of critical illness complicated by acute kidney injury requiring renal replacement therapy (RRT) are at an increased risk of dialysis dependence and death but the mechanisms are unknown. Methods In a multicenter, prospective, cohort study of 817 critically ill patients receiving RRT, we examined association between Day 1 plasma inflammatory [interleukin (IL)-1β, IL-6, IL-8, IL-10 and IL-18; macrophage migration inhibitory factor (MIF) and tumor necrosis factor]; apoptosis [tumor necrosis factor receptor (TNFR)-I and TNFR-II and death receptor (DR)-5]; and growth factor (granulocyte macrophage colony stimulating factor) biomarkers and renal recovery and mortality at Day 60. Renal recovery was defined as alive and RRT independent. Results Of 817 participants, 36.5% were RRT independent and 50.8% died. After adjusting for differences in demographics, comorbid conditions; premorbid creatinine; nephrotoxins; sepsis; oliguria; mechanical ventilation; RRT dosing; and severity of illness, increased concentrations of plasma IL-8 and IL-18 and TNFR-I were independently associated with slower renal recovery [adjusted hazard ratio (AHR) range for all markers, 0.70-0.87]. Higher concentrations of IL-6, IL-8, IL-10 and IL-18; MIF; TNFR-I and DR-5 were associated with mortality (AHR range, 1.16-1.47). In an analysis of multiple markers simultaneously, increased IL-8 [AHR, 0.80, 95% confidence interval (95% CI) 0.70-0.91, P < 0.001] and TNFR-I (AHR, 0.63, 95% CI 0.50-0.79, P < 0.001) were associated with slower recovery, and increased IL-8 (AHR, 1.26, 95% CI 1.14-1.39, P < 0.001); MIF (AHR, 1.18, 95% CI 1.08-1.28, P < 0.001) and TNFR-I (AHR, 1.26, 95% CI 1.02-1.56, P < 0.03) were associated with mortality. Conclusions Elevated plasma concentrations of inflammatory and apoptosis biomarkers are associated with RRT dependence and death. Our data suggest that future interventions should investigate broad-spectrum immune-modulation to improve outcomes.

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DO - 10.1093/ndt/gfu051

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