Cytokine gene promoter polymorphisms and mortality in acute renal failure

Cytokine. 2004 Mar 7;25(5):212-9. doi: 10.1016/j.cyto.2003.11.004.


Background: Although cytokines play a pivotal role in the inflammatory responses that mediate the severity of acute renal failure (ARF), the importance of pro- and anti-inflammatory cytokine gene promoter polymorphisms has been unexplored.

Methods: We prospectively evaluated the relationship of single nucleotide polymorphism in the promoter region of tumor necrosis factor alpha (TNF-alpha) and interleukin-10 (IL-10) to mortality in 61 patients with ARF requiring intermittent hemodialysis. Cytokine genotyping was performed on leukocytes using PCR techniques. Cox proportional-hazards regression analysis was used to explore these relationships.

Results: The mean (+/-SD) APACHE II score was 24 +/- 7, MOF score 2 +/- 1, and 64% had sepsis. The TNF-alpha high producer genotype (-308 A-allele carrier) was associated with a higher risk of death after adjustment for the APACHE II score (HR=2.5; P=0.04), and the IL-10 intermediate/high producer genotype (-1082 G-allele carrier) was associated with a lower risk of death after adjustment for the MOF score (HR=0.36; P=0.03). Considering combinations of genotypes, the TNF-alpha high and IL-10 low producer genotype combination was associated with a approximately 6-fold increased risk of death compared to the TNF-alpha-low and IL-10 intermediate/high producer genotype combination, after adjustment for either APACHE II (P=0.004), MOF score (P=0.004) or sepsis (P=0.006).

Conclusions: TNF-alpha and IL-10 gene polymorphisms are related to the risk of death among patients with ARF who require dialysis. Larger studies are needed to confirm these relationships.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Kidney Injury / genetics*
  • Acute Kidney Injury / mortality*
  • Acute Kidney Injury / pathology
  • Aged
  • Female
  • Gene Frequency
  • Humans
  • Interleukin-10 / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Genetic / genetics*
  • Promoter Regions, Genetic / genetics*
  • Severity of Illness Index
  • Tumor Necrosis Factor-alpha / genetics*


  • Tumor Necrosis Factor-alpha
  • Interleukin-10