title: Urinary cystatin C and NGAL as early biomarkers for assessment of renal ischemia-reperfusion injury: a serum marker to replace creatinine?
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Urology, Tulane University School of Medicine , New Orleans, Louisiana.
authors.forename: Benjamin W
authors.initials: BW
authors.lastname: Woodson
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.forename: Sree
authors.initials: S
authors.lastname: Mandava
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Lee
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism / Q000652:urine*; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000652:urine; D016022:Case-Control Studies; D003404:Creatinine / Q000097:blood*; D055316:Cystatin C / Q000097:blood / Q000652:urine*; D004195:Disease Models, Animal; D005919:Glomerular Filtration Rate; D006801:Humans; D007668:Kidney / Q000098:blood supply*; D007674:Kidney Diseases / Q000097:blood / Q000652:urine*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine*; D008297:Male; D011518:Proto-Oncogene Proteins / Q000652:urine*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000097:blood / Q000652:urine*; D013997:Time Factors
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; D055316:Cystatin C; C097278:Lcn2 protein, rat; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D000493:Allopurinol; D003404:Creatinine