title: Cytokine phenotype, genotype, and renal outcomes at cardiac surgery.
abstract: BACKGROUND
  Cardiac surgery modulates pro- and anti-inflammatory cytokine balance involving plasma tumour necrosis factor alpha (TNFα) and interleukin-10 (IL-10) together with urinary transforming growth factor beta-1 (TGFβ1), interleukin-1 receptor antagonist (IL1ra) and tumour necrosis factor soluble receptor-2 (TNFsr2). Effects on post-operative renal function are unclear. We investigated if following cardiac surgery there is a relationship between cytokine (a) phenotype and renal outcome; (b) genotype and phenotype and (c) genotype and renal outcome. Since angiotensin-2 (AG2), modulates TGFβ1 production, we determined whether angiotensin converting enzyme insertion/deletion (ACE I/D) genotype affects urinary TGFβ1 phenotype as well as renal outcome.
  
  
  METHODS
  In 408 elective cardiac surgery patients we measured pre- and 24 h post-operative urinary TGFβ-1, IL1ra and TNFsr2 and pre- and 2 h post-operative plasma TNFα and IL-10. Post-operative responses were compared for each cytokine in patients grouped according to presence or absence of renal dysfunction defined as a drop from baseline eGFR of greater than 25% (as calculated by the method of modification of diet in renal disease (MDRD)) occurring (1) within the first 24 and (2) 48 postoperative hours (early renal dysfunction), (3) on the fifth postoperative day (late renal dysfunction) or (4) at any time throughout the 5 day postoperative period (early and late combined). Patient genotype was determined for TNF/G-308A, TGFβ1-509 C/T, IL10/G-1082A and ACE I/D.
  
  
  RESULTS
  Post-operative plasma IL-10 and urinary TGFβ1 responses were significantly higher in patients who developed early renal dysfunction. IL1ra and TNFsr2 responses were significantly lower 24h post-operatively in patients who developed late renal dysfunction. Genotype did not alter cytokine phenotype or outcome. CONCLUSIONS/INFERENCES: Cytokine profiling may help predict early and late renal dysfunction. Genotypes studied did not alter phenotype or outcome.
authors.affiliation: Department of Cardiac Anaesthesia, Belfast Health & Social Care Trust, Belfast BT12 6BA, Northern Ireland, UK. williamthomasmcb@doctors.org.uk
authors.forename: William T
authors.initials: WT
authors.lastname: McBride
authors.forename: Penugonda S
authors.initials: PS
authors.lastname: Prasad
authors.forename: Marilyn
authors.initials: M
authors.lastname: Armstrong
authors.forename: Christopher
authors.initials: C
authors.lastname: Patterson
authors.forename: Helen
authors.initials: H
authors.lastname: Gilliland
authors.forename: Andrew
authors.initials: A
authors.lastname: Drain
authors.forename: Alain
authors.initials: A
authors.lastname: Vuylsteke
authors.forename: Ray
authors.initials: R
authors.lastname: Latimer
authors.forename: Nadia
authors.initials: N
authors.lastname: Khalil
authors.forename: Alun
authors.initials: A
authors.lastname: Evans
authors.forename: François
authors.initials: F
authors.lastname: Cambien
authors.forename: Ian
authors.initials: I
authors.lastname: Young
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology* / Q000235:genetics; D000368:Aged; D000085962:Angiotensin-Converting Enzyme 2; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D016207:Cytokines / Q000097:blood* / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D007674:Kidney Diseases / Q000209:etiology* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D010641:Phenotype; D053773:Transforming Growth Factor beta1 / Q000097:blood; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D016207:Cytokines; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2