Plasma and urinary cytokine homeostasis and renal dysfunction during cardiac surgery.
BACKGROUND
Cardiac surgery induces changes in plasma cytokines. Proinflammatory cytokines have been associated with a number of renal diseases. The proinflammatory cytokines interleukin 8 (IL-8), tumor necrosis factor alpha (TNFalpha), and interleukin 1beta (IL-1beta) are smaller than the antiinflammatory cytokines interleukin 10 (IL-10), interleukin 1 receptor antagonist (IL-1ra), and TNF soluble receptor 2 (TNFsr2), and thus undergo glomerular filtration more readily. Accordingly, this study investigated the relation between plasma and urinary cytokines and proximal renal dysfunction during cardiac surgery.


METHODS
Twenty patients undergoing coronary artery bypass grafting with cardiopulmonary bypass (CPB) were studied. Blood and urine samples were analyzed for proinflammatory and antiinflammatory cytokines. Proximal tubular dysfunction was measured using urinary N-acetyl-beta-d-glucosaminidase (NAG)/creatinine and alpha1-microglobulin/creatinine ratios.


RESULTS
Plasma IL-8, IL-10, IL-1ra, and TNFsr2 values were significantly elevated compared with baseline. Urinary IL-1ra and TNFsr2 were significantly elevated. Urinary NAG/creatinine and alpha1-microglobulin/creatinine ratios were also elevated. Plasma TNFalpha at 2 h correlated with urinary NAG/creatinine ratio at 2 and 6 h (P < 0.05) and with urinary IL-1ra at 2 h (P < 0.05). Plasma IL-8 at 2 h correlated with NAG/creatinine at 6 h (P < 0.05). Urinary IL-1ra correlated with urinary NAG/creatinine ratio after cross-clamp release and 2 and 6 h after CPB (P < 0.05).


CONCLUSIONS
Cardiac surgery using CPB leads to changes in plasma and urinary cytokine homeostasis that correlate with renal proximal tubular dysfunction. This dysfunction may be related to the renal filtration of proinflammatory mediators. Renal autoprotective mechanisms may involve the intrarenal generation of antiinflammatory cytokines.
Gormley
S M
SM
Departments of Anaesthetics and Intensive Care, and Microbiology and Immunobiology, The Queen's University of Belfast, Belfast, Northern Ireland.
McBride
W T
WT
Armstrong
M A
MA
Young
I S
IS
McClean
E
E
MacGowan
S W
SW
Campalani
G
G
McMurray
T J
TJ
D000118:Acetylglucosaminidase / Q000652:urine; D000510:Alpha-Globulins / Q000652:urine; D015415:Biomarkers / Q000652:urine; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D001026:Coronary Artery Bypass / Q000009:adverse effects*; D003404:Creatinine / Q000652:urine; D016207:Cytokines / Q000097:blood / Q000378:metabolism* / Q000652:urine; D005260:Female; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000378:metabolism; D007674:Kidney Diseases / Q000097:blood / Q000209:etiology* / Q000378:metabolism* / Q000652:urine; D007687:Kidney Tubules, Proximal / Q000503:physiopathology; D008297:Male; D008875:Middle Aged
D000510:Alpha-Globulins; D015415:Biomarkers; D016207:Cytokines; C016001:alpha-1-microglobulin; D003404:Creatinine; D000118:Acetylglucosaminidase