High levels of cell-free DNA accurately predict late acute kidney injury in patients after cardiac surgery

Abstract

Use of cardiopulmonary bypass in cardiac surgery triggers systemic inflammation by neutrophil activation leading to neutrophil extracellular traps (NETs) release. Hence, nuclear DNA released by necrotic and apoptotic cells might contribute to an increase in circulating cell-free DNA (cfDNA). cfDNA/NETs might induce endothelial damage and organ dysfunction. This study focuses on the accuracy of cfDNA to predict acute kidney injury (AKI) after on-pump surgery. 58 cardiac patients undergoing on-pump surgery were prospectively enrolled. Blood samples were taken preoperatively, immediately after surgery, at day 1, 2, 3 and 5 from patients with (n = 21) or without (n = 37) postoperative AKI development. Levels of cfDNA, neutrophil gelatinase-associated lipocalin (NGAL) and creatinine in patients' plasma were quantified. ROC curves were used to assess the predictive value of the biomarkers for AKI. Further baseline characteristics and perioperative variables were analyzed.cfDNA and NGAL levels highly increased in AKI patients and significant intergroup differences (vs. non-AKI) were found until day 3 and day 5 after surgery, respectively. cfDNA levels were significantly elevated in patients who developed late AKI (>24 hours), but not in those with AKI development during the first 24 hours (early AKI). NGAL and creatinine, which were highest in patients with early AKI, accurately predicted during the first 24 postoperative hours (early AKI). At day 3, at a threshold of 260.53 ng/ml cfDNA was the best predictor for AKI (AUC = 0.804) compared to NGAL (AUC = 0.699) and creatinine (AUC = 0.688). NGAL, but not cfDNA, was strongly associated with AKI stages and mortality. Monitoring of cfDNA levels from the first postoperative day might represent a valuable tool to predict late AKI after on-pump surgery.

Conflict of interest statement

The authors declared that no competing interests exist.

Figures

Fig 1. Kinetics of cfDNA/NETs and NGAL in patients undergoing cardiac surgery with CPB.

cfDNA (A) and NGAL (B) levels were quantified in plasma of patients with (n = 21,) or without (n = 37) postoperative AKI development at the indicated times. &p

Fig 2. ROC curves.

ROC curves at admission, post-surgery, day 1, day 2 and day 3 for AKI prediction.

Fig 3. Kinetics of cfDNA/NETs, NGAL and creatinine in patients with early and late postoperative AKI development.

AKI patients were divided into those with diagnosed AKI during the first 24 hours after surgery (early AKI) and those with AKI development at later times (late AKI). cfDNA (A), NGAL (B) and creatinine (C) concentrations were quantified at the defined times. &p

Fig 4. Association of disease severity and mortality with cfDNA and NGAL.

(A) cfDNA and NGAL were compared between patients with stage 1 (n = 14) and stage 2(n = 7) AKI. Receiver operating characteristic curves were performed for the prediction of tsgae 2 AKI. (B) cfDNA and NGAL levels in patients in survivors and patients who died during 1-year follow-up. Receiver operating characteristic curves were performed for the prediction of mortality in AKI patients.