Plasma interleukin-6 predicts cardiovascular mortality in hemodialysis patients.
BACKGROUND
Interleukin-6 (IL-6) is a mediator and marker of the chronic inflammatory process that is responsible for much of the morbidity and mortality seen in hemodialysis (HD) patients. This study evaluated circulating plasma IL-6 as a predictor of all-cause mortality and cardiovascular mortality and studied its relationship to prevalent comorbidity and hypoalbuminemia, in a cohort of stable HD patients enrolled in the HEMO study.


METHODS
Clinical data included demographic, medical, and routine laboratory parameters. Comorbidities were graded using the Index of Co-Existing Diseases (ICED). Outcomes of interest were all-cause mortality and cardiovascular mortality. Blood samples were drawn at enrollment and annually, and plasma IL-6 levels measured with high-sensitivity enzyme-linked immunosorbent assay.


RESULTS
Median plasma IL-6 level in 206 patients was 7.9 pg/mL (range, 0.1 to 90.3 pg/mL) and was higher in patients with vascular disease ( P = 0.03), higher ICED scores ( P = 0.01), and lower Karnofsky indices ( P < 0.01). Serum albumin was inversely related to plasma IL-6 levels ( P = 0.03, r = -0.16). Unadjusted median survival time was 1,209 days in the lowest quartile of plasma IL-6 and 806 days in the highest ( P = 0.02, log rank test). A 1-log increase in plasma IL-6 was associated with a 1.19-fold higher adjusted risk for all-cause mortality ( P = 0.04; 95% confidence interval, 1.01 to 1.40) and a 1.43-fold higher adjusted risk of cardiovascular mortality ( P = 0.02; 95% confidence interval, 1.06 to 1.92). Hazard ratio estimates were higher when IL-6 levels over time were incorporated as a time-dependent covariate.


CONCLUSIONS
Plasma IL-6 levels are strongly associated with comorbidity in HD patients and are a powerful predictor of cardiovascular and all-cause mortality.
Rao
Madhumathi
M
Division of Nephrology, Tufts-New England Medical Center, Boston, MA 02111, USA.
Guo
Daqing
D
Perianayagam
Mary C
MC
Tighiouart
Hocine
H
Jaber
Bertrand L
BL
Pereira
Brian J G
BJ
Balakrishnan
Vaidyanathapuram S
VS
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000401:mortality*; D015897:Comorbidity / Q000639:trends; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D006435:Renal Dialysis / Q000379:methods*; D012709:Serum Albumin / Q000378:metabolism; D014508:Urea / Q000097:blood / Q000378:metabolism / Q000652:urine; D001613:beta 2-Microglobulin / Q000097:blood / Q000378:metabolism / Q000652:urine
D015415:Biomarkers; D015850:Interleukin-6; D012709:Serum Albumin; D001613:beta 2-Microglobulin; D014508:Urea