Cytokine gene promoter polymorphisms and mortality in acute renal failure.
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.
Jaber
Bertrand L
BL
Division of Nephrology, Tufts-New England Medical Center, Boston, MA 02111, USA. bjaber@tufts-nemc.org
Rao
Madhumathi
M
Guo
Daqing
D
Balakrishnan
Vaidyanathapuram S
VS
Perianayagam
Mary C
MC
Freeman
Richard B
RB
Pereira
Brian J G
BJ
D058186:Acute Kidney Injury / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D000368:Aged; D005260:Female; D005787:Gene Frequency; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10