Predictive Value of Plasma NGAL:Hepcidin-25 for Major Adverse Kidney Events After Cardiac Surgery with Cardiopulmonary Bypass: A Pilot Study

Abstract

Background Neutrophil gelatinase-associated lipocalin (NGAL) and hepcidin-25 are involved in catalytic iron-related kidney injury after cardiac surgery with cardiopulmonary bypass. We explored the predictive value of plasma NGAL, plasma hepcidin-25, and the plasma NGAL:hepcidin-25 ratio for major adverse kidney events (MAKE) after cardiac surgery. Methods We compared the predictive value of plasma NGAL, hepcidin-25, and plasma NGAL:hepcidin-25 with that of serum creatinine (Cr) and urinary output and protein for primary-endpoint MAKE (acute kidney injury [AKI] stages 2 and 3, persistent AKI >48 hours, acute dialysis, and in-hospital mortality) and secondary-endpoint AKI in 100 cardiac surgery patients at intensive care unit (ICU) admission. We performed ROC curve, logistic regression, and reclassification analyses. Results At ICU admission, plasma NGAL, plasma NGAL:hepcidin-25, plasma interleukin-6, and Cr predicted MAKE (area under the ROC curve [AUC]: 0.77, 0.79, 0.74, and 0.74, respectively) and AKI (0.73, 0.89, 0.70, and 0.69). For AKI prediction, plasma NGAL:hepcidin-25 had a higher discriminatory power than Cr (AUC difference 0.26 [95% CI 0.00–0.53]). Urinary output and protein, plasma lactate, C-reactive protein, creatine kinase myocardial band, and brain natriuretic peptide did not predict MAKE or AKI (AUC <0.70). Only plasma NGAL:hepcidin-25 correctly reclassified patients according to their MAKE and AKI status (category-free net reclassification improvement: 0.82 [95% CI 0.12–1.52], 1.03 [0.29–1.77]). After adjustment to the Cleveland risk score, plasma NGAL:hepcidin-25 ≥0.9 independently predicted MAKE (adjusted odds ratio 16.34 [95% CI 1.77–150.49], P =0.014). Conclusions Plasma NGAL:hepcidin-25 is a promising marker for predicting postoperative MAKE.

Neutrophil Gelatinase-Associated Lipocalin Cutoff Value Selection and Acute Kidney Injury Classification System Determine Phenotype Allocation and Associated Outcomes

“…Nevertheless, the internal validity of our findings is strengthened by the similarities in risk variability within two independent, well-defined cardiac surgery cohorts with a consequent timing of biomarker sampling. We do not preclude the conclusion that other biomarkers for AKI risk prediction may also be affected by changing biomarker threshold selections [39].…”

Urinary and plasma hepcidin-25 as indicators of labile iron involvement in acute kidney injury after cardiac surgery

“…This may possibly indicate a nephroprotective property through the interaction with reactive iron compounds since hepcidin-25 synthesis is physiologically increased by iron overload [ 6 ]. In our study cohort, this pattern of higher hepcidin-25 levels in patients without AKI described for urine samples ( P = 0.001 for 6 h and 24 h) [ 5 ] could not be demonstrated in patients’ plasma samples at 6 h and even less so at 24 h after CS with P = 0.189 and P = 0.652, respectively ( Figure 1 ) [ 2 ]. This is of interest as it may suggest that urinary biomarkers might be more sensitive for histological damage (i.e., tubular injury) than plasma biomarkers.…”

“…In a recent study, we compared the predictive value of plasma Neutrophil Gelatinase–Associated Lipocalin (NGAL), hepcidin-25, and plasma NGAL:hepcidin-25-ratio with that of serum creatinine and urinary output for primary-endpoint MAKE (acute kidney injury [AKI] stages 2 and 3, persistent AKI >48 h, acute dialysis, and in-hospital mortality) and secondary-endpoint AKI in 100 on-pump CS patients at intensive care unit (ICU) admission (corresponding to 6 h). We performed receiver operator characteristic (ROC) curve, logistic regression, and reclassification analyses [ 2 ]. Out of 100 patients, 9 developed MAKE and 9 developed AKI, respectively.…”

Hepcidin-25 as a Novel Kidney Biomarker for Cardiac Surgery-Associated Acute Kidney Injury

“…In this issue, Albert C, et al [ 4 ] reported that plasma NGAL:hepcidin-25 is a promising marker for predicting postoperative major adverse kidney events after cardiac surgery. In their previous study, considering laboratory and clinical availability of the biomarkers, they concluded that NGAL and interleukin-6 appear to be the most excellent candidates for implementation in kidney risk assessment [ 2 ].…”

“…In this time, the authors newly presented the roles of plasma NGAL:hepcidin-25 in maintaining the homeostasis of labile-iron during and after cardiac surgery [ 4 ]. Consistent with recent reports showing changes of both urinary and plasma hepcidin-25 concentrations, their results also suggested that lower concentrations of hepcidin-25 are independently associated with increased mortality in critically ill patients with AKI requiring KRT [ 4 ].…”