Urinary Cystatin C and NGAL as Early Biomarkers for Assessment of Renal Ischemia-Reperfusion Injury: A Serum Marker to Replace Creatinine?

Purpose: To assess application of cystatin C and neutrophil gelatinase-associated lipocalin (NGAL) as biomarkers for renal ischemic injury. We also evaluated the use of allopurinol as a renoprotective agent. A second goal was to assess cystatin C as a biomarker in patients undergoing partial nephrectomy. Methods: Using 58 Sprague-Dawley rats, we evaluated urinary cystatin C (n=26) and NGAL (n=32) as a biomarker for renal ischemia injury. Half of the rats were pretreated with allopurinol; the other cohort served as a control. The right renal hilum was ligated in all rats, thereby creating a solitary kidney model. After a 30-minute stabilization period, the left hilum was clamped for time periods of 15, 30, and 60 minutes. Urinary levels of cystatin C and NGAL were then measured at the following time points: Preclamp (after the 30-minute stabilization period) and postclamp (30, 45, and 60 minute periods after unclamping). For our clinical subjects, serum cystatin C levels (n=17) were obtained preoperatively, at the induction of anesthesia before robot-assisted partial nephrectomy, immediately postoperatively, and on postoperative days 1 and 2. Three of these patients had their tumors excised off clamp and served as controls. We then estimated glomerular filtration rate by using the Creatinine-Cystatin C Equation. Results: Urinary levels of cystatin C and NGAL increased after renal clamping. The 30-minute period of ischemia demonstrated the greatest increase of these biomarkers. Allopurinol did appear to serve a renoprotective function in those animals undergoing 30-minute clamp times. In our clinical patients, the serum cystatin C levels did increase at each postoperative time point, but remained nonelevated in the control group. Conclusions: Cystatin C and NGAL both appear to be useful biomarkers of renal injury. Studies with larger numbers are needed, however. Also, allopurinol does exhibit renoprotective effects against ischemic injury.