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

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.

Biomarker-Guided Risk Assessment for Acute Kidney Injury: Time for Clinical Implementation?

Acute kidney injury (AKI) is a common and serious complication in hospitalized patients, which continues to pose a clinical challenge for treating physicians. The most recent Kidney Disease Improving Global Outcomes practice guidelines for AKI have restated the importance of earliest possible detection of AKI and adjusting treatment accordingly. Since the emergence of initial studies examining the use of neutrophil gelatinase-associated lipocalin (NGAL) and cycle arrest biomarkers, tissue inhibitor metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein (IGFBP7), for early diagnosis of AKI, a vast number of studies have investigated the accuracy and additional clinical benefits of these biomarkers. As proposed by the Acute Dialysis Quality Initiative, new AKI diagnostic criteria should equally utilize glomerular function and tubular injury markers for AKI diagnosis.In addition to refining our capabilities in kidney risk prediction with kidney injury biomarkers, structural disorder phenotypes referred to as “preclinical-” and “subclinical AKI” have been described and are increasingly recognized. Additionally, positive biomarker test findings were found to provide prognostic information regardless of an acute decline in renal function (positive serum creatinine criteria). We summarize and discuss the recent findings focusing on two of the most promising and clinically available kidney injury biomarkers, NGAL and cell cycle arrest markers, in the context of AKI phenotypes. Finally, we draw conclusions regarding the clinical implications for kidney risk prediction.

Urinary Biomarkers may Complement the Cleveland Score for Prediction of Adverse Kidney Events After Cardiac Surgery: A Pilot Study

BACKGROUND: The ability of urinary biomarkers to complement established clinical risk prediction models for postoperative adverse kidney events is unclear. We assessed the effect of urinary biomarkers linked to suspected pathogenesis of cardiac surgery-induced acute kidney injury (AKI) on the performance of the Cleveland Score, a risk assessment model for postoperative adverse kidney events. METHODS: This pilot study included 100 patients who underwent open-heart surgery. We determined improvements to the Cleveland Score when adding urinary biomarkers measured using clinical laboratory platforms (neutrophil gelatinase-associated lipocalin [NGAL], interleukin-6) and those in the preclinical stage (hepcidin-25, midkine, alpha-1 microglobulin), all sampled immediately post-surgery. The primary endpoint was major adverse kidney events (MAKE), and the secondary endpoint was AKI. We performed ROC curve analysis, assessed baseline model performance (odds ratios [OR], 95% CI), and carried out statistical reclassification analyses to assess model improvement. RESULTS: NGAL (OR [95% CI] per 20 concentration-units wherever applicable): (1.07 [1.01–1.14]), Interleukin-6 (1.51 [1.01–2.26]), midkine (1.01 [1.00–1.02]), 1-hepcidin-25 (1.08 [1.00–1.17]), and NGAL/hepcidin-ratio (2.91 [1.30–6.49]) were independent predictors of MAKE and AKI (1.38 [1.03–1.85], 1.08 [1.01–1.15], 1.01 [1.00–1.02], 1.09 [1.01–1.18], and 3.45 [1.54–7.72]). Category-free net reclassification improvement identified interleukin-6 as a model-improving biomarker for MAKE and NGAL for AKI. However, only NGAL/hepcidin-25 improved model performance for event- and event-free patients for MAKE and AKI. CONCLUSIONS: NGAL and interleukin-6 measured immediately post cardiac surgery may complement the Cleveland Score. The combination of biomarkers with hepcidin-25 may further improve diagnostic discrimination.