TY - JOUR
T1 - Plasma cytokine levels predict mortality in patients with acute renal failure
AU - Simmons, Edith M.
AU - Himmelfarb, Jonathan
AU - Tugrul Sezer, M.
AU - Chertow, Glenn M.
AU - Mehta, Ravindra L.
AU - Paganini, Emil P.
AU - Soroko, Sharon
AU - Freedman, Stephanie
AU - Becker, Karen
AU - Spratt, Daniel
AU - Shyr, Yu
AU - Alp Ikizler, T.
N1 - Funding Information:
This work is supported in part by NIH grants R01 DK53411, DK53412, DK53413, and 1K24 DK62849. Dr. Edith Simmons is supported by NIH grant 2T32 DK07569 and K12 RR17697. Dr. M. Tugrul Sezer is supported by International Society of Nephrology Fellowship Training Grant. This work was presented in abstract form at the 35th Annual Meeting and Scientific Exposition of the American Society of Nephrology, Philadelphia, PA, November, 2002.
PY - 2004/4
Y1 - 2004/4
N2 - 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 antiinflammatory 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)-1β, IL-6, IL-8, tumor necrosis factor-α (TNF-α)], 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.
AB - 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 antiinflammatory 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)-1β, IL-6, IL-8, tumor necrosis factor-α (TNF-α)], 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.
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U2 - 10.1111/j.1523-1755.2004.00512.x
DO - 10.1111/j.1523-1755.2004.00512.x
M3 - Article
C2 - 15086475
AN - SCOPUS:12144289562
SN - 0085-2538
VL - 65
SP - 1357
EP - 1365
JO - Kidney international
JF - Kidney international
IS - 4
ER -
