NGAL/hepcidin-25 ratio and AKI subtypes in patients following cardiac surgery: a prospective observational study

Abstract

Background: Acute kidney injury (AKI) subtypes combining kidney functional parameters and injury biomarkers may have prognostic value. We aimed to determine whether neutrophil gelatinase-associated lipocalin (NGAL)/hepcidin-25 ratio (urinary concentrations of NGAL divided by that of hepcidin-25) defined subtypes are of prognostic relevance in cardiac surgery patients.

Methods: We studied 198 higher-risk cardiac surgery patients. We allocated patients to four groups: Kidney Disease Improving Global Outcomes (KDIGO)-AKI-negative and NGAL/hepcidin-25 ratio-negative (no AKI), KDIGO AKI-negative and NGAL/hepcidin-25 ratio-positive (subclinical AKI), KDIGO AKI-positive and NGAL/hepcidin-25 ratio-negative (clinical AKI), KDIGO AKI-positive and NGAL/hepcidin-25 ratio-positive (combined AKI). Outcomes included in-hospital mortality (primary) and long-term mortality (secondary).

Results: We identified 127 (61.6%) patients with no AKI, 13 (6.6%) with subclinical, 40 (20.2%) with clinical and 18 (9.1%) with combined AKI. Subclinical AKI patients had a 23-fold greater in-hospital mortality than no AKI patients. For combined AKI vs. no AKI or clinical AKI, findings were stronger (odds ratios (ORs): 126 and 39, respectively). After adjusting for EuroScore, volume of intraoperative packed red blood cells, and aortic cross-clamp time, subclinical and combined AKI remained associated with greater in-hospital mortality than no AKI and clinical AKI (adjusted ORs: 28.118, 95% CI 1.465-539.703; 3.737, 95% CI 1.746-7.998). Cox proportional hazard models found a significant association of biomarker-informed AKI subtypes with long-term survival compared with no AKI (adjusted ORs: pooled subclinical and clinical AKI: 1.885, 95% CI 1.003-3.542; combined AKI: 1.792, 95% CI 1.367-2.350).

Conclusions: In the presence or absence of KDIGO clinical criteria for AKI, the urinary NGAL/hepcidin-25-ratio appears to detect prognostically relevant AKI subtypes.

Trial registration number: NCT00672334, clinicaltrials.gov, date of registration: 6th May 2008, https://clinicaltrials.gov/ct2/show/NCT00672334 . Definition of AKI subtypes: subclinical AKI (KDIGO negative AND Ratio-positive), clinical AKI (KDIGO positive AND Ratio-negative) and combined AKI (KDIGO positive AND Ratio-positive) with urinary NGAL/hepcidin-25 ratio-positive cut-off at 85% specificity for in-hospital death. AKI, acute kidney injury. AUC, area under the curve. NGAL, neutrophil gelatinase-associated lipocalin. KDIGO, Kidney Disease Improving Global Outcomes Initiative AKI definition.

Keywords: Cardiopulmonary bypass; Cardiorenal syndrome; NGAL/hepcidin-25 ratio; Subclinical AKI.

Fig. 1

In-hospital mortality grouped by AKI subtypes. Urinary NGAL/hepcidin-25 ratio after end of surgery (–), if ratio < 0.5, NGAL/hepcidin-25 ratio after end of surgery ( +), if ratio ≥ 0.5. Underlying table shows odds ratios and 95% confidence interval (CI) for risk assessment between groups. NGAL urine neutrophil gelatinase-associated lipocalin, KDIGO-AKI acute kidney injury according to the KDIGO criteria [2]

Fig. 2

Long-term survival according to AKI subtypes. NGAL/hepcidin-25 ratio and allocated AKI subtype: log-rank test p < 0.001. Follow up time was 5.6 years. NGAL neutrophil gelatinase-associated lipocalin. Urinary NGAL and hepcidin-25 concentrations and NGAL/hepcidin-25 ratio immediately after end of surgery were available for all 198 patients. KDIGO-AKI acute kidney injury according to the KDIGO criteria [2]