Plasma cytokine levels predict mortality in patients with acute renal failure.

Abstract

BACKGROUND:

Critically ill patients with acute renal failure (ARF) experience a high mortality rate. Animal and human studies suggest that proinflammatory cytokines lead to the development of a systemic inflammatory response syndrome (SIRS), which is temporally followed by a counter anti-inflammatory response syndrome (CARS). This process has not been specifically described in critically ill patients with ARF.

METHODS:

The Program to Improve Care in Acute Renal Disease (PICARD) is a prospective, multicenter cohort study designed to examine the natural history, practice patterns, and outcomes of treatment in critically ill patients with ARF. In a subset of 98 patients with ARF, we measured plasma proinflammatory cytokines [interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor-alpha (TNF-alpha)], the acute-phase reactant C-reactive protein (CRP), and the anti-inflammatory cytokine IL-10 at study enrollment and over the course of illness.

RESULTS:

When compared with healthy subjects and end-stage renal disease patients on maintenance hemodialysis, patients with ARF had significantly higher plasma levels of all measured cytokines. Additionally, the proinflammatory cytokines IL-6 and IL-8 were significantly higher in nonsurvivors versus survivors [median 234.7 (interdecile range 64.8 to 1775.9) pg/mL vs. 113.5 (46.1 to 419.3) pg/mL, P= 0.02 for IL-6; 35.5 (14.1 to 237.9) pg/mL vs. 21.2 (8.5 to 87.1) pg/mL, P= 0.03 for IL-8]. The anti-inflammatory cytokine IL-10 was also significantly higher in nonsurvivors [3.1 (0.5 to 41.9) pg/mL vs. 2.4 (0.5 to 16.9) pg/mL, P= 0.04]. For each natural log unit increase in the levels of IL-6, IL-8, and IL-10, the odds of death increased by 65%, 54%, and 34%, respectively, corresponding to increases in relative risk of approximately 30%, 25%, and 15%. The presence or absence of SIRS or sepsis was not a major determinant of plasma cytokine concentration in this group of patients.

CONCLUSION:

There is evidence of ongoing SIRS with concomitant CARS in critically ill patients with ARF, with higher levels of plasma IL-6, IL-8, and IL-10 in patients with ARF who die during hospitalization. Strategies to modulate inflammation must take into account the complex cytokine biology in patients with established ARF.

• Authors: Edith M Simmons, Jonathan Himmelfarb, M Tugrul Sezer, Glenn M Chertow, Ravindra L Mehta, Emil P Paganini, Sharon Soroko, Stephanie Freedman, Karen Becker, Daniel Spratt, Yu Shyr, T Alp Ikizler, PICARD Study Group
• Journal: Kidney international (Kidney Int) Vol. 65 Issue 4 Pg. 1357-65 (Apr 2004) ISSN: 0085-2538 [Print] United States
• PMID: 15086475 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Biomarkers
• Cytokines
• Inflammation Mediators
• Interleukin-6
• Interleukin-8
• Interleukin-10
• C-Reactive Protein

Topics

• Acute Kidney Injury (blood, complications, mortality)
• Aged
• Biomarkers (blood)
• C-Reactive Protein (metabolism)
• Case-Control Studies
• Cohort Studies
• Critical Illness
• Cytokines (blood)
• Female
• Humans
• Inflammation (metabolism)
• Inflammation Mediators (blood)
• Interleukin-10 (blood)
• Interleukin-6 (blood)
• Interleukin-8 (blood)
• Kidney Failure, Chronic (blood, therapy)
• Male
• Middle Aged
• Predictive Value of Tests
• Prospective Studies
• Renal Dialysis
• Systemic Inflammatory Response Syndrome (complications)