Associations of interleukin-6, C-reactive protein and serum amyloid A with mortality in haemodialysis patients.
BACKGROUND
Individuals with end-stage renal disease (ESRD) manifest a chronic inflammatory state. Serum albumin, C-reactive protein (CRP), interleukin-6 (IL-6) and serum amyloid A (SAA) have been associated with mortality in ESRD, although reports vary as to whether they are true independent markers of mortality. We undertook a prospective study to determine whether these markers could predict mortality in ESRD.


METHODS
A cohort of individuals on haemodialysis was followed prospectively for a mean of 2.1 years. Albumin, CRP, IL-6 and SAA were drawn at enrollment. Association between mortality and serum markers was assessed using Cox proportional hazards regression. A trend analysis was undertaken to establish the functional form of the association between serum markers and outcome.


RESULTS
After multivariable adjustment, IL-6 was most strongly associated with mortality, followed closely by albumin (P = 0.0002 and P = 0.0005, respectively). CRP was marginally associated with mortality (P = 0.046), and SAA was not independently associated with mortality. In the final model adjusting for the effects of both IL-6 and albumin simultaneously, both markers remained associated with mortality (P = 0.003 and P = 0.011).


CONCLUSIONS
IL-6 had the strongest independent association with mortality, followed closely by albumin. CRP and SAA were not associated with mortality when measured at single time points. Increasing levels of IL-6 and decreasing levels of albumin were associated with increased mortality. IL-6 and albumin may be capturing different aspects of the inflammatory burden observed in haemodialysis patients.
Wetmore
James B
JB
Department of Medicine, San Francisco VAMC/University of California, California, USA. jwetmore@kumc.edu
Lovett
David H
DH
Hung
Adriana M
AM
Cook-Wiens
Galen
G
Mahnken
Jonathan D
JD
Sen
Saunak
S
Johansen
Kirsten L
KL
D000328:Adult; D000368:Aged; D015415:Biomarkers; D002097:C-Reactive Protein / Q000032:analysis* / Q000502:physiology; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D006435:Renal Dialysis / Q000401:mortality*; D012709:Serum Albumin / Q000032:analysis; D000685:Serum Amyloid A Protein / Q000032:analysis*
D015415:Biomarkers; D015850:Interleukin-6; D012709:Serum Albumin; D000685:Serum Amyloid A Protein; D002097:C-Reactive Protein