Urinary Hepcidin-25 and Risk of Acute Kidney Injury Following Cardiopulmonary Bypass

Background and objectives Acute kidney injury (AKI) complicating cardiopulmonary bypass (CPB) results in increased morbidity and mortality. Urinary hepcidin-25 has been shown to be elevated in patients who do not develop AKI after CPB using semiquantitative mass spectrometry (SELDI TOF-MS). The goals of this study were to quantitatively validate these findings with ELISA and evaluate the diagnostic performance of hepcidin-25 for AKI. Design, setting, participants, & measurements A nested, case-control analysis of urinary hepcidin-25 in AKI (n = 22) and non-AKI (n = 22) patients was conducted to validate the SELDI TOF-MS data at the following times: preoperatively; the start of CPB; 1 hour on CPB; on arrival to the intensive care unit; and postoperative days (POD) 1 and 3 to 5. The diagnostic performance of hepcidin-25 was then evaluated in the entire prospective observational cohort (n = 338) at POD 1. AKI was defined as Cr >50% from baseline, within 72 hours postoperatively. Results Urinary hepcidin-25/Cr ratio was significantly elevated in all patients at POD 1 compared with baseline (P < 0.0005) and was also significantly elevated in non-AM versus AKI patients at POD 1 (P < 0.0005). Increased logic, hepcidin-25/Cr ratio was strongly associated with avoidance of AM on univariate analysis. On multivariate analysis, the logic, hepcidin-25/Cr ratio (P < 0.0001) was associated with avoidance of AM with an area under the curve of 0.80, sensitivity 0.68, specificity 0.68, and negative predictive value 0.96. Conclusions Elevated urinary hepcidin-25 on POD 1 is a strong predictor of avoidance of AKI beyond postoperative day 1. Clin I Am Soc Nephrol 6: 2340-2346, 2011. doi: 10.2215/CJN.01000211