Small increases in the urinary excretion of glutathione S-transferase A1 and P1 after cardiac surgery are not associated with clinically relevant renal injury

Objective: Cardiac surgery is an important risk factor for the development of acute renal failure. Cytosolic enzymes glutathione S-transferase (GST) A1 and P1 are present selectively in proximal and distal tubular cells, respectively. We determined the extent and site of tubular injury and examined if GST excretion may predict a clinically relevant change in renal function. Design and setting: A prospective, observational study in 84 consecutive patients in the cardiac surgery intensive care unit of the University Medical Centre Nijmegen. Measurements and results: Urinary GST enzyme excretion was determined 0-4 h and 20-24 h after cardiac surgery by enzyme-linked immunosorbent assay. Data are expressed as median and 5-95% range. Urinary excretion of GSTA1 was increased: 1.25 mu g/mmol [0.31-10.20] creatinine at t = 0-4 h ( p < 0.0001, compared with controls; 0.25 [0.1-0.8]) and returned to normal values at t = 20-24 h. Excretion of GSTP1 was 2.11 mu g/mmol [0.52-17.82] creatinine ( p < 0.0001) at t = 0-4 h and remained significantly elevated: 0.84 [0.30-16.86] at t = 20-24 h ( p =0.01) compared with controls (0.5 [0.2-1.1]). The ten patients with the highest urinary excretion of GSTA1 or GSTP1 did not demonstrate a different plasma creatinine level on postoperative day 3, compared with the ten patients with the lowest urinary excretion of GSTA1 or GSTP1. Conclusion : Uncomplicated cardiac surgery results in a statistically significant increase in the urinary excretion of GSTA1 and GSTP1 as compared with healthy controls, indicating proximal and distal tubular damage. However, this small increase in urinary excretion of GSTs is not associated with clinically relevant renal injury.