title: Methylprednisolone favourably alters plasma and urinary cytokine homeostasis and subclinical renal injury at cardiac surgery.
abstract: Whilst elevated urinary transforming growth factor beta-1 (TGFbeta) is associated with chronic renal dysfunction its role in acute peri-operative renal dysfunction is unknown. In contrast, peri-operative increases in urinary IL-1 receptor antagonist (IL-1ra) and TNF soluble receptor-2 (TNFsr-2) mirror pro-inflammatory activity in the nephron and correlate with renal complications. Steroids modulate some plasma cytokines (decreasing TNFalpha, IL-8, IL-6 and increasing IL-10), whereas ability to reduce plasma and urinary TNFsr-2 and IL-1ra and peri-operative renal injury is unknown. Patients undergoing coronary artery bypass grafting with cardiopulmonary bypass (CPB) were randomised to receive methylprednisolone (n = 18) or placebo (n = 17) before induction of anaesthesia. Plasma and urinary pro- and anti-inflammatory cytokine balance was determined along with subclinical proximal tubular injury and dysfunction, measured by urinary N-acetyl-beta-d-glucosaminidase (NAG)/creatinine and alpha-1-microglobulin/creatinine ratios, respectively. In the control group compared with baseline, plasma IL-8, TNFalpha, IL-10, IL-1ra and TNFsr-2 were significantly elevated along with urinary IL-1ra, TNFsr-2 and TGFbeta1. Urinary NAG/creatinine and alpha-1-microglobulin/creatinine ratios rose from completion of revascularisation until 6 h with recovery at 24 h with a further rise in NAG/creatinine ratio at 48 h. Compared to placebo, the methylprednisolone group showed significantly reduced plasma IL-8, TNFalpha, IL-1ra and TNFsr-2 whereas plasma IL-10 increased. Compared to placebo, the methylprednisolone group demonstrated significantly reduced urinary NAG/creatinine ratio, TNFsr-2 and TGFbeta1 at 24 h whereas urinary alpha-1-microglobulin/creatinine ratios increased.
  
  
  CONCLUSIONS
  Methylprednisolone administration during cardiac surgery significantly reduces plasma and urinary TNFsr-2 and IL-1ra, urinary TGFbeta1 and subclinical renal injury but not dysfunction.
authors.affiliation: Department of Anaesthetics and Intensive Care Medicine, The Queen's University of Belfast, Belfast, Northern Ireland, Ireland. williamthomasmcb@aol.com
authors.forename: William T
authors.initials: WT
authors.lastname: McBride
authors.forename: Stephen
authors.initials: S
authors.lastname: Allen
authors.forename: Sheena M C
authors.initials: SM
authors.lastname: Gormley
authors.forename: Ian S
authors.initials: IS
authors.lastname: Young
authors.forename: Elizabeth
authors.initials: E
authors.lastname: McClean
authors.forename: Simon W
authors.initials: SW
authors.lastname: MacGowan
authors.forename: Peter
authors.initials: P
authors.lastname: Elliott
authors.forename: Terence J
authors.initials: TJ
authors.lastname: McMurray
authors.forename: Marilyn A
authors.initials: MA
authors.lastname: Armstrong
mesh_terms: D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D002315:Cardiopulmonary Bypass; D001026:Coronary Artery Bypass; D016207:Cytokines / Q000097:blood* / Q000652:urine*; D005260:Female; D006706:Homeostasis; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007674:Kidney Diseases / Q000209:etiology* / Q000517:prevention & control; D007687:Kidney Tubules, Proximal / Q000473:pathology*; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage*; D008875:Middle Aged; D012795:Sialoglycoproteins / Q000097:blood / Q000652:urine
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D012795:Sialoglycoproteins; D008775:Methylprednisolone