Plasma cytokine levels predict mortality in patients with acute renal failure

Simmons, Edith; Himmelfarb, Jonathan; Sezer, Mehmet Tuğrul; Chertow, Glenn M.; Mehta, Ravindra L.; Paganini, Emil P.; Soroko, Sharon; Freedman, Steven J.; Becker, Karen; Spratt, Daniel; Shyr, Yu; Ikizler, Talp; Group, for the PICARD Study

doi:10.1111/j.1523-1755.2004.00512.x

Cited by 392 publications

(324 citation statements)

References 31 publications

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“…However, to date, direct proinflammatory cytokine manipulation (e.g., TNF-␣ and IL-1 pathway interruption) in patients with established sepsis has not been fruitful (37)(38)(39). Increased plasma levels of IL-6 predict mortality in patients with sepsis and in patients with sepsis and acute kidney disease (40,41). We have shown that IL-6 also predicts the development of AKI and need for RRT in patients with SS.…”

Section: Discussionmentioning

confidence: 82%

Elevated Plasma Concentrations of IL-6 and Elevated APACHE II Score Predict Acute Kidney Injury in Patients with Severe Sepsis

Chawla¹,

Seneff²,

Nelson³

et al. 2007

Clinical Journal of the American Society of Nephrology

170

103

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Acute kidney injury (AKI) is common in critically ill patients with severe sepsis (SS), and the predictors of AKI in this population have not been well characterized. The study group was the placebo group of the Prospective Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) data set. PROWESS is a prospective, randomized, controlled study of the use of drotrecogin ␣ (activated) for the treatment of SS. Placebo patients who had an admission renal sepsis organ failure score of 2 or more were excluded. AKI was defined as an increase in serum creatinine of 25% or 0.3 mg/dl during the first week postbaseline. The incidence of relevant parameters was then compared in patients with and without AKI. Half of the patients were randomly assigned to a model-building data set, and multivariable Cox regression was used to determine risk factors. Factors that remained significant in the remaining "model validation" data set were considered significant. Of the 840 patients in the placebo group, 547 met inclusion criteria. Of the 547 patients, 127 (23.2%) patients met criteria for AKI. The mean age of the 547 patients was 59.8 ؎ 17.0, and 43.3% of the cohort were female. The ethnicity breakdown was as follows: White 83.2%, black 5.9%, and other 11%. Univariate analyses indicated that patients with AKI had a higher incidence of a dependence on the basis of activity of daily living scale (38.6 versus 26.7%; P ‫؍‬ 0.01), a lower baseline platelet count (193,000 versus 222,000; P ‫؍‬ 0.02), a higher baseline respiratory Sepsis Organ Failure Assessment score (2.9 versus 2.7; P ‫؍‬ 0.02), higher preinfusion Acute Physiology and Chronic Health Evaluation II (APACHE II) score (24.8 versus 22.0; P ‫؍‬ 0.0002), older age (63.7 versus 58.7 yr; P ‫؍‬ 0.008), and higher log IL-6 (6.6 versus 5.8; P ‫؍‬ 0.0006). In a multivariable Cox regression, the predictors of AKI were log IL-6 (P < 0.0001) and APACHE II (P ‫؍‬ 0.0008). Increased log IL-6 and APACHE II score are significant risk factors of AKI in patients with SS. IL-6 data and the absence of correlation with measures of hypotension (e.g., mean arterial pressure, dosage of vasopressors) support the notion that inflammation is a significant component of AKI in SS.

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Section: Discussionmentioning

confidence: 82%

Elevated Plasma Concentrations of IL-6 and Elevated APACHE II Score Predict Acute Kidney Injury in Patients with Severe Sepsis

Chawla¹,

Seneff²,

Nelson³

et al. 2007

Clinical Journal of the American Society of Nephrology

170

103

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“…We suggest that the exuberant proinflammatory response in AKI contributes to the development of respiratory failure, which may be less in ESRD. Proinflammatory cytokines such as IL-6, IL-8 and TNF-α are increased in patients with AKI, 16 and increased levels of IL-6 and IL-8 predicted prolonged mechanical ventilation in patients with AKI. 15 The inflammatory nature of AKI and the resultant effect on the lungs is highlighted by studies in animal models demonstrating that inflammatory genes are up-regulated in the kidney and lung 32 and that anti-inflammatory treatment with IL-6 inhibition, 33 α-MSH 34 or a p38 MAP kinase inhibitor 35 protect against lung injury in animal models of AKI.…”

Section: Discussionmentioning

confidence: 99%

“…For example, increased proinflammatory cytokines associated with AKI may contribute to extra-renal organ dysfunction such as acute lung injury (ALI). [13][14][15][16] Furthermore, recent attention has been given to the role of fluid overload as a factor associated with increased mortality in patients with AKI. [17][18][19] Many of the factors associated with increased mortality in patients with AKI are likely to be absent in patients with end-stage renal disease (ESRD).…”

Section: Introductionmentioning

confidence: 99%

In Critically Ill Patients Requiring CRRT, AKI Is Associated with Increased Respiratory Failure and Death Versus ESRD

et al. 2011

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Background/aims: To compare outcomes of critically ill patients with acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT) versus those with pre-existing end-stage renal disease (ESRD) requiring CRRT to identify factors that contribute to the increased mortality seen in AKI patients. Methods: Retrospective cohort of 257 intensive care unit (ICU) patients who received CRRT. AKI is defined as requiring CRRT with an admission serum creatinine ≤1 mg/dL; ESRD is defined as chronic dialysis dependence. Primary outcome was hospital mortality. Multivariate logistic regression was performed to determine the impact of APACHE II score, intubation, vasopressors, infection, diabetes, hypertension, gender, and race on mortality. Results: Of 257 patients requiring CRRT, 28 had ESRD and 108 had AKI. Hospital mortality was higher in patients with AKI versus ESRD (69% vs. 39%, p = 0.0032). Severity of illness using APACHE II was similar in AKI and ESRD. Patients with AKI were more likely to require mechanical ventilation (89% vs. 57%, p = 0.0003). After multivariate analysis, the requirement for mechanical ventilation was the single factor associated with increased hospital mortality [odds ratio (OR): 3.1]. Conclusions: In ICU patients requiring CRRT, patients with AKI have a higher mortality than patients with ESRD due to an increased need for mechanical ventilation.

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“…Similarly, infusion of a tumor necrosis factor (TNF)-α binding protein decreased neutrophil infiltration and preserved renal function, suggesting a deleterious role for the upregulation of TNF-α in renal I/R (136). In addition, levels of the pro-inflammatory cytokines IL-6 and IL-8 in plasma have been found to predict mortality in patients with acute renal failure (137).…”

Section: Activation Of Inflammation and Endothelial-leukocyte Interacmentioning

confidence: 99%

Renal Hypoxia and Dysoxia After Reperfusion of the Ischemic Kidney

Legrand

Mik

Johannes³

et al. 2008

Mol Med

237

169

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Ischemia is the most common cause of acute renal failure. Ischemic-induced renal tissue hypoxia is thought to be a major component in the development of acute renal failure in promoting the initial tubular damage. Renal oxygenation originates from a balance between oxygen supply and consumption. Recent investigations have provided new insights into alterations in oxygenation pathways in the ischemic kidney. These findings have identified a central role of microvascular dysfunction related to an imbalance between vasoconstrictors and vasodilators, endothelial damage and endothelium-leukocyte interactions, leading to decreased renal oxygen supply. Reduced microcirculatory oxygen supply may be associated with altered cellular oxygen consumption (dysoxia), because of mitochondrial dysfunction and activity of alternative oxygen-consuming pathways. Alterations in oxygen utilization and/or supply might therefore contribute to the occurrence of organ dysfunction. This view places oxygen pathways' alterations as a potential central player in the pathogenesis of acute kidney injury. Both in regulation of oxygen supply and consumption, nitric oxide seems to play a pivotal role. Furthermore, recent studies suggest that, following acute ischemic renal injury, persistent tissue hypoxia contributes to the development of chronic renal dysfunction. Adaptative mechanisms to renal hypoxia may be ineffective in more severe cases and lead to the development of chronic renal failure following ischemia-reperfusion. This paper is aimed at reviewing the current insights into oxygen transport pathways, from oxygen supply to oxygen consumption in the kidney and from the adaptation mechanisms to renal hypoxia. Their role in the development of ischemia-induced renal damage and ischemic acute renal failure are discussed.

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Plasma cytokine levels predict mortality in patients with acute renal failure

Cited by 392 publications

References 31 publications

Elevated Plasma Concentrations of IL-6 and Elevated APACHE II Score Predict Acute Kidney Injury in Patients with Severe Sepsis

Elevated Plasma Concentrations of IL-6 and Elevated APACHE II Score Predict Acute Kidney Injury in Patients with Severe Sepsis

In Critically Ill Patients Requiring CRRT, AKI Is Associated with Increased Respiratory Failure and Death Versus ESRD

Renal Hypoxia and Dysoxia After Reperfusion of the Ischemic Kidney

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