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.

• Authors: 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, Biological Markers for Recovery of Kidney (BioMaRK) Study Investigators
• Journal: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association (Nephrol Dial Transplant) Vol. 29 Issue 10 Pg. 1854-64 (Oct 2014) ISSN: 1460-2385 [Electronic] England
• PMID: 24619058 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Observational Study, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Chemical References

• Biomarkers
• Cytokines
• Receptors, Death Domain

Topics

• Acute Kidney Injury (blood, mortality, therapy)
• Biomarkers (blood)
• Case-Control Studies
• Critical Illness (mortality)
• Cytokines (blood)
• Female
• Humans
• Male
• Middle Aged
• Prognosis
• Prospective Studies
• Receptors, Death Domain (blood)
• Renal Dialysis (mortality)
• Survival Rate