Methylprednisolone favourably alters plasma and urinary cytokine homeostasis and subclinical renal injury at cardiac surgery.

Abstract Whilst elevated urinary transforming growth factor beta-1 (TGFβ) 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 TNFα, 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-β- d -glucosaminidase (NAG)/creatinine and α-1-microglobulin/creatinine ratios, respectively. In the control group compared with baseline, plasma IL-8, TNFα, IL-10, IL-1ra and TNFsr-2 were significantly elevated along with urinary IL-1ra, TNFsr-2 and TGFβ1. Urinary NAG/creatinine and α-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, TNFα, 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 TGFβ1 at 24 h whereas urinary α-1-microglobulin/creatinine ratios increased. Conclusions Methylprednisolone administration during cardiac surgery significantly reduces plasma and urinary TNFsr-2 and IL-1ra, urinary TGFβ1 and subclinical renal injury but not dysfunction.