title: Plasma and urinary cytokine homeostasis and renal function during cardiac surgery without cardiopulmonary bypass.
abstract: Cardiopulmonary bypass (CPB) significantly contributes to the plasma pro-inflammatory cytokine response at cardiac surgery. Complementary plasma and urinary anti-inflammatory cytokine responses have been described. The pro-inflammatory cytokines interleukin 8 (IL-8), tumour necrosis factor alpha (TNF-alpha) and interleukin 1beta (IL-1beta) have lower molecular weights than the anti-inflammatory cytokines interleukin 10 (IL-10), interleukin 1 receptor antagonist (IL-1ra) and TNF soluble receptor 2 (TNFsr2) and thus undergo glomerular filtration more readily. In vitro work suggests that proximal tubular cells are vulnerable to pro-inflammatory cytokine mediated injury. Accordingly, this study investigated the hypothesis that cardiac surgery without CPB would not have significant changes in plasma and urinary cytokines and proximal renal dysfunction. Eight patients undergoing coronary artery bypass grafting (CABG) without CPB were studied. Blood and urine samples were analysed for pro- and anti-inflammatory cytokines. Proximal tubular dysfunction was measured using urinary Nu-acetyl-beta-D-glucosaminidase (NAG)/creatinine and alpha(1)-microglobulin/creatinine ratios. Plasma IL-8, IL-10, IL-1ra and TNFsr2 were significantly elevated compared with baseline. Urinary IL-1ra and TNFsr2 were significantly elevated, as were urinary NAG/creatinine and alpha(1)-microglobulin/creatinine ratios. Two hours following revascularization, urinary IL-1ra correlated with urinary alpha(1)-microglobulin/creatinine ratios (P<0.05). As previously reported in CABG surgery with CPB, we now report that non-CPB cardiac surgery also has significant changes in plasma and urinary cytokine homeostasis and early proximal tubular injury. The correlation between urinary IL-1ra and alpha(1)-microglobulin/creatinine ratios is consistent with earlier suggestions of a mechanistic link between cytokine changes and proximal tubular dysfunction. The relative roles of CPB and non-CPB processes in producing inflammation still require definition.
authors.affiliation: Department of Anaesthetics and Intensive Care, The Queen's University of Belfast, Belfast, Northern Ireland, UK.
authors.forename: S M C
authors.initials: SM
authors.lastname: Gormley
authors.forename: William Thomas
authors.initials: WT
authors.lastname: McBride
authors.forename: M A
authors.initials: MA
authors.lastname: Armstrong
authors.forename: E
authors.initials: E
authors.lastname: McClean
authors.forename: S W
authors.initials: SW
authors.lastname: MacGowan
authors.forename: G
authors.initials: G
authors.lastname: Campalani
authors.forename: T J
authors.initials: TJ
authors.lastname: McMurray
mesh_terms: D000118:Acetylglucosaminidase / Q000652:urine; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000097:blood / Q000652:urine; D002315:Cardiopulmonary Bypass; D001026:Coronary Artery Bypass / Q000009:adverse effects*; D003404:Creatinine / Q000097:blood / Q000652:urine; D016207:Cytokines / Q000097:blood* / Q000652:urine*; D005260:Female; D006706:Homeostasis; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000097:blood / Q000652:urine; D016753:Interleukin-10 / Q000097:blood / Q000652:urine; D016209:Interleukin-8 / Q000097:blood / Q000652:urine; D007687:Kidney Tubules, Proximal / Q000293:injuries* / Q000503:physiopathology; D008297:Male; D008562:Membrane Glycoproteins / Q000652:urine; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D047889:Receptors, Tumor Necrosis Factor, Type II; D012795:Sialoglycoproteins / Q000097:blood / Q000652:urine; D013903:Thoracic Surgery; D014360:Trypsin Inhibitor, Kunitz Soybean; D014409:Tumor Necrosis Factor-alpha / Q000652:urine
chemical_list: D015703:Antigens, CD; D016207:Cytokines; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D016209:Interleukin-8; D008562:Membrane Glycoproteins; D018124:Receptors, Tumor Necrosis Factor; D047889:Receptors, Tumor Necrosis Factor, Type II; C109148:SPINT2 protein, human; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D014360:Trypsin Inhibitor, Kunitz Soybean; D003404:Creatinine; D000118:Acetylglucosaminidase