The effect of etanercept on suppression of the systemic inflammatory response in chronic hemodialysis patients.
BACKGROUND
Inflammation strongly predicts all-cause and cardiovascular mortality among dialysis patients. The negative acute-phase proteins, albumin and prealbumin are both inversely associated with mortality. Both albumin and prealbumin levels are decreased by inflammation. We carried out a pilot study to establish whether treatment with the tumor necrosis factor-alpha; receptor antagonist etanercept would be safe and result in improved levels of albumin and prealbumin in inflamed hypoalbuminemic (albumin < 3.8 g/dl, CRP > 8.0 mg/l) prevalent hemodialysis patients.


METHODS
We excluded patients who had infectious risk (hepatitis C or B positive, HIV positive, purified protein derivative (PPD) positive or having a history of tuberculosis, having a tunneled dialysis catheter) to find patients having both hypoalbuminemia and inflammation. Of 433 less than 6% met the inclusion criteria. 10 patients were randomized to receive etanercept or placebo twice weekly for 44 weeks.


RESULTS
There were no adverse infectious events. There was no significant difference for any of the measurements between the two groups. However there was a significant difference in the time-dependent effects of etanercept on prealbumin: increasing 20% in the etanercept group while decreasing in the placebo group.


CONCLUSIONS
Administration of a TNF-alpha; receptor antagonist appears safe in this selected population, despite the large increase in infectious risk observed in the dialysis patient population. The effect on surrogate markers of inflammation is small.
Don
B R
BR
Division of Nephrology, University of California Davis School of Medicine and the UC Davis Medical Center, Davis, CA, USA.
Kim
K
K
Li
J
J
Dwyer
T
T
Alexander
F
F
Kaysen
G A
GA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000068800:Etanercept; D005260:Female; D006801:Humans; D034141:Hypoalbuminemia / Q000097:blood / Q000188:drug therapy; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007249:Inflammation / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011228:Prealbumin / Q000032:analysis; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D006435:Renal Dialysis; D012709:Serum Albumin / Q000032:analysis
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007074:Immunoglobulin G; D011228:Prealbumin; D018124:Receptors, Tumor Necrosis Factor; D012709:Serum Albumin; D000068800:Etanercept