Original Investigations: Pathogenesis and Treatment of Kidney Disease and Hypertension
Elevated serum levels of the type I and type II receptors for tumor necrosis factor-α as predictive factors for ARF in patients with septic shock,★★

https://doi.org/10.1053/ajkd.2003.50024Get rights and content

Abstract

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-α (TNF-α) or interleukin-6 between patients with and without ARF, elevated serum levels of the two soluble TNF-α 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 (≤124 μmol/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. Am J Kidney Dis 41:62-75. © 2003 by the National Kidney Foundation, Inc.

Section snippets

Methods

We analyzed data from the placebo limb of the Norasept II database. Details of the Norasept II study have been previously published.23

In brief, adults older than 18 years who were admitted to the hospital with septic shock and who met all the following clinical criteria were eligible for enrollment: (1) duration of shock less than 12 hours, (2) clinical evidence of acute infection, (3) core temperature greater than 38.3°C (101°F) or less than 35.6°C (96°F), (4) tachycardia (heart rate > 90

Analysis of entire cohort

To determine factors that correlate with the development of ARF among patients presenting with sepsis and/or SIRS, we retrospectively analyzed multiple routinely available demographic, clinical, and laboratory variables, all obtained at the time of enrollment in a large multicenter study of septic shock.

Five hundred thirty-seven patients were available for analysis, of whom 112 patients (20%) developed ARF. There was no statistically significant difference in causes of septic shock among

Discussion

In this report, we evaluate the association between the development and outcome of ARF with various clinical and laboratory variables, including systemic levels of proinflammatory cytokines, among 537 patients with sepsis and/or SIRS. These patients were enrolled in the placebo arm of the Norasept II study, a multicenter, randomized, double-blind, placebo-controlled trial comparing the administration of antihuman TNF-α mAb with placebo.23 Our most important finding is the significant

Acknowledgements

The authors thank Thomas E. Mansfield III, Senior Clinical Programmer Analyst, Bayer Corp, for invaluable help in preparing the data for analysis.

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    For the Norasept II Study Investigators.

    Supported in part by grants no. DK59793 (J.S.L.) and HL69722 (J.S.L.) from The National Institutes of Health.

    Address reprint requests to Jose Iglesias, DO, 11 Paulette Ln, Howell NJ 07731. E-mail: [email protected]

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