Urine hepcidin has additive value in ruling out cardiopulmonary bypass-associated acute kidney injury: an observational cohort study

Anja Haase-Fielitz, Peter R Mertens, Michael Plass, Hermann Kuppe, Roland Hetzer, Mark Westerman, Vaughn Ostland, John R Prowle, Rinaldo Bellomo, Michael Haase, Anja Haase-Fielitz, Peter R Mertens, Michael Plass, Hermann Kuppe, Roland Hetzer, Mark Westerman, Vaughn Ostland, John R Prowle, Rinaldo Bellomo, Michael Haase

Abstract

Introduction: Conventional markers of acute kidney injury (AKI) lack diagnostic accuracy and are expressed only late after cardiac surgery with cardiopulmonary bypass (CPB). Recently, interest has focused on hepcidin, a regulator of iron homeostasis, as a unique renal biomarker.

Methods: We studied 100 adult patients in the control arm of a randomized, controlled trial http://www.clinicaltrials.gov/NCT00672334 who were identified as being at increased risk of AKI after cardiac surgery with CPB. AKI was defined according to the Risk, Injury, Failure, Loss, End-stage renal disease classification of AKI classification stage. Samples of plasma and urine were obtained simultaneously (1) before CPB (2) six hours after the start of CPB and (3) twenty-four hours after CPB. Plasma and urine hepcidin 25-isoforms were quantified by competitive enzyme-linked immunoassay.

Results: In AKI-free patients (N = 91), urine hepcidin concentrations had largely increased at six and twenty-four hours after CPB, and they were three to seven times higher compared to patients with subsequent AKI (N = 9) in whom postoperative urine hepcidin remained at preoperative levels (P = 0.004, P = 0.002). Furthermore, higher urine hepcidin and, even more so, urine hepcidin adjusted to urine creatinine at six hours after CPB discriminated patients who did not develop AKI (area under the curve (AUC) receiver operating characteristic curve 0.80 [95% confidence interval (95% CI) 0.71 to 0.87] and 0.88 [95% CI 0.78 to 0.97]) or did not need renal replacement therapy initiation (AUC 0.81 [95% CI 0.72 to 0.88] 0.88 [95% CI 0.70 to 0.99]) from those who did. At six hours, urine hepcidin adjusted to urine creatinine was an independent predictor of ruling out AKI (P = 0.011). Plasma hepcidin did not predict no development of AKI. The study findings remained essentially unchanged after excluding patients with preoperative chronic kidney disease.

Conclusions: Our findings suggest that urine hepcidin is an early predictive biomarker of ruling out AKI after CPB, thereby contributing to early patient risk stratification.

Figures

Figure 1
Figure 1
Patient flow through the study http://www.clinicaltrials.gov/NCT00672334. CPB, cardiopulmonary bypass.
Figure 2
Figure 2
Urine hepcidin concentration over time. Patients not developing acute kidney injury (AKI) (white bars) are compared to those with AKI (hatched bars) (A) for all patients and (B) after excluding patients with chronic kidney disease (CKD). Error bars at top and bottom define th 95% confidence interval and the black lines within boxes the medians.
Figure 3
Figure 3
Plasma hepcidin concentration over time. Patients not developing AKI (white bars) are compared to those with AKI (hatched bars) (A) for all patients and (B) after excluding patients with CKD. Error bars at top and bottom define th 95% confidence interval and the black lines within boxes the medians.
Figure 4
Figure 4
Predictive indices of hepcidin at six hours after commencement of CPB for not developing AKI. (A) Urine hepcidin. (B) Urine hepcidin/urine creatinine. (C) Plasma hepcidin. AUC-ROC, area under the curve receiver operating characteristic curve.
Figure 5
Figure 5
Predictive indices of hepcidin at six hours for not requiring postoperative renal replacement therapy initiation. (A) Urine hepcidin. (B) Urine hepcidin/urine creatinine. (C) Plasma hepcidin.

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