DYNAMIC TRAJECTORIES OF 4-HOUR CREATININE CLEARANCE AND URINARY POST-TRANSLATIONALLY MODIFIED FETUIN-A AMONG PATIENTS UNDERGOING CARDIOPULMONARY BYPASS: WELCOMING NEW ALLIES IN DETECTING AKI

Acute kidney injury (AKI) is a common complication among patients undergoing cardiopulmonary bypass (CPB), a procedure known to cause immediate ischemia–reperfusion injury to the kidneys and increase mortality risk. This study aims to compare the diagnostic performance, particularly the timeliness of detection, among conventional rapid changes in serum creatinine (S-Cre), 4-hour dynamic creatinine clearance (dCCR4), urinary neutrophil gelatinase–associated lipocalin (uNGAL), and a novel urinary biomarker, Post-Translationally Modified Fetuin-A (uPTM-FetA). 

Between 2021 and 2023, we prospectively enrolled 19 patients undergoing CPB at a tertiary medical center in Taiwan. Following a standardized regional protocol, blood and urine samples were collected during bypass, every 8 hours for the first 48 hours after surgery, and then daily through postoperative day 7. AKI was defined using conventional KDIGO (Kidney Disease Improving Global Outcomes) criteria as a ≥50% increase in S-Cre within 7 days or an increase of ≥0.3 mg/dL within 48 hours, urine output <0.5 mL/kg/h for 6 hours, or dCCR4 criteria as a ≥25% decline in dCCR4 compared with baseline. uNGAL was measured using a chemiluminescent microparticle immunoassay (ARCHITECT Urine NGAL Assay; Abbott Diagnostics, Abbott Park, IL, USA), while urinary PTM-FetA levels were measured using the Human uPTM3-DKD ELISA kit (CE-IVD marked; Bio Preventive Medicine Corp, Zhubei City, Taiwan; trade name: DNlite-IVD103). Biomarker concentrations (ng/mL) were normalized to urine creatinine (mg/dL) and reported as ng/mg. We applied generalized linear mixed models to characterize the temporal trajectories of the log-transformed biomarkers between -12 hours to 48 hours of the bypass time. Each model included a natural cubic spline for time to capture nonlinear trends, a subject-specific random intercept and a first-order autoregressive residual structure to model within-patient correlation.

Among the 19 participants, the median age was 66.0 years (IQR, 57.0–71.0), 7 were women (36.8%), and the baseline median serum creatinine was 0.87 mg/dL (0.76–0.97). Sixteen patients (84.2%) met the KDIGO or dCCR4 criteria for AKI; two required temporary in-hospital dialysis, and one of them died during hospitalization. The median duration of CPB was 3.0 (2.6–3.5) hours. The median time to peak levels of uNGAL and uPTM-FetA was both 5.5 hours, with IQR of 4.5–6.3 and 3.7–33.0 hours, respectively. The trajectories of uNGAL and uPTM-FetA were highly correlated, showing consistent temporal patterns with similar peak and plateau dynamics from baseline to the first 48 hours of bypass (Figure 1). For dCCR4 and S-Cre–based KDIGO criteria, the median time to AKI were 7 (0–7) and 11 (11–11) hours, respectively (p<0.001). dCCR4 demonstrated a continuous, earlier, and steeper decline until reaching its trough, in contrast to eGFR, which showed a transient hyperfiltration pattern that may delay AKI detection (Figure 2).

uPTM-FetA exhibited a dynamic trajectory comparable to that of uNGAL following CPB, and dCCR4 remained a useful marker for earlier AKI detection. Further studies are warranted to validate the prognostic value of both novel injury biomarkers and dCCR4 approaches, either individually or in combination.