MO410URINARY NGAL:HEPCIDIN-25 RATIO VERSUS URINARY NGAL FOR EARLY IDENTIFICATION OF PATIENTS AT RISK FOR ACUTE RENAL REPLACEMENT THERAPY AND DEATH AFTER CARDIAC SURGERY
Authors: Elitok Saban , Haase-Fielitz Anja , Ernst Martin , Haase Michael 
Published: May 2021

Abstract

Background and Aims
Acute kidney injury requiring renal replacement therapy (AKI-RRT) is strongly associated with mortality after cardiac surgery, however, options for early identification of patients at high-risk for AKI-RRT are extremely limited. Early after cardiac surgery, the predictive ability for AKI-RRT even of one of the most extensively evaluated novel urinary biomarkers, neutrophil gelatinase-associated lipocalin (NGAL), appears to be only moderate. We aimed to determine whether the discriminatory power and reclassification indices of NGAL:hepcidin-25-ratio (urinary concentrations of NGAL divided by that of hepcidin-25) within 60 min after end of surgery compare favorably to NGAL alone for identification of high-risk patients after cardiac surgery. We also aimed to determine whether an increased NGAL:hepcidin-25-ratio can detect subclinical AKI (no serum creatinine- or urine output-based criteria for AKI).

Method
This is a prospective substudy of the BICARBONATE trial, a multicenter parallel-randomized controlled trial comparing perioperative bicarbonate infusion for AKI prevention to usual patient care. At a tertiary referral center, 198 patients at increased kidney risk undergoing cardiac surgery with cardiopulmonary bypass were included into the present study. The primary outcome measure was defined as AKI-RRT. Secondary outcomes were in-hospital mortality and ratio-defined subclinical AKI characterized by increased odds for AKI-RRT or in-hospital mortality. We compared biomarkers’ area-under-the-curve of the receiver-operating-characteristic and performed cross-validated reclassification statistics and regression analysis adjusted to Cleveland risk score/EuroScore, cross-clamp time, age and volume of packed red blood cells.

Results
Patients with AKI-RRT (n=13) had 13.7-times higher NGAL and 3.3-times lower hepcidin-25 concentrations resulting in 46.9-times higher NGAL:hepcidin-25-ratio early after surgery compared to patients without AKI-RRT (Figure 1). The NGAL:hepcidin-25-ratio had higher discriminatory power compared with NGAL for risk of AKI-RRT and in-hospital mortality (area-under-the-curve difference 0.087, 95% CI, 0.036 to 0.138, P&lt;0.001; 0.082, 95% CI, 0.018 to 0.146, P=0.012). The NGAL:hepcidin-25-ratio, but not NGAL, was independently associated with AKI-RRT (adjusted OR per 1-SD higher lnNGAL:hepcidin-25-ratio, 1.524, 95% CI, 1.046 to 2.222, P=0.028). The NGAL:hepcidin-25-ratio increased category-free net-reclassification-improvement for AKI-RRT (0.690, 95% CI, 0.146 to 1.234, P=0.013) and in-hospital mortality (cfNRI 0.744, 95% CI, 0.201 to 1.288, P=0.007). NGAL:hepcidin-25-ratio-positive subclinical AKI was associated with increased AKI-RRT (OR 10.02, 95% CI, 1.59 to 63.39; P&lt;0.001) and in-hospital mortality rates (OR 41.07, 95% CI, 4.31 to 391.40; P&lt;0.001).

Conclusion
The urinary NGAL:hepcidin-25-ratio appears to early identify high-risk patients and outperform NGAL after cardiac surgery. Also, the urinary NGAL:hepcidin-25 ratio can detect subclinical AKI. Confirmation of our findings in other cardiac surgery centers is now needed.