Elevated serum levels of the type I and type II receptors for tumor necrosis factor-alpha as predictive factors for ARF in patients with septic shock

Am J Kidney Dis. 2003 Jan;41(1):62-75. doi: 10.1053/ajkd.2003.50024.


Background: Acute renal failure (ARF), a common and serious complication in patients with septic shock, has high mortality. Recent data suggest that proinflammatory cytokines may contribute to sepsis-associated ARF.

Methods: To examine the role of proinflammatory cytokines, we evaluated 537 patients enrolled in the placebo arm of the Norasept II study, of whom 112 patients (20%) developed ARF.

Results: By univariate analysis, the following factors were significantly associated with the development of ARF: male sex, younger age, increased heart rate, higher Acute Physiology and Chronic Health Evaluation II score, oliguria, increased blood urea nitrogen level, increased serum creatinine (Scr) level, decreased arterial pH, and increased serum potassium level. Although there were no statistically significant differences in serum levels of tumor necrosis factor-alpha (TNF-alpha) or interleukin-6 between patients with and without ARF, elevated serum levels of the two soluble TNF-alpha receptors (S-TNF-RI and S-TNF-RII) were strongly associated with the development of ARF (S-TNF-RI, 25 +/- 16 versus 18 +/- 13 ng/mL; P = 0.00006; S-TNF-RII, 25 +/- 21 versus 18 +/- 17 ng/mL; P = 0.0007). Using forward stepwise regression analysis, elevated S-TNF-R level remained an independent predictor for ARF, even when we limited our analysis to patients with Scr levels of 1.4 mg/dL or less (< or =124 micromol/L) at study entry, suggesting that decreased renal clearance of S-TNF-R alone cannot account for this association. Elevated S-TNF-R level also was an independent predictor of mortality among patients developing ARF.

Conclusion: S-TNF-R level is an independent predictor for the development of ARF and mortality. We speculate that elevated S-TNF-R levels may reflect a more intense inflammatory response.

Publication types

  • Clinical Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Kidney Injury / blood*
  • Acute Kidney Injury / etiology*
  • Acute Kidney Injury / mortality
  • Analysis of Variance
  • Antigens, CD / blood*
  • Female
  • Humans
  • Interleukin-6 / blood
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Placebo Effect
  • Placebos / therapeutic use
  • Predictive Value of Tests
  • Receptors, Tumor Necrosis Factor / blood*
  • Receptors, Tumor Necrosis Factor, Type I
  • Receptors, Tumor Necrosis Factor, Type II
  • Risk Factors
  • Shock, Septic / blood*
  • Shock, Septic / complications
  • Shock, Septic / drug therapy


  • Antigens, CD
  • Interleukin-6
  • Placebos
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type I
  • Receptors, Tumor Necrosis Factor, Type II