Urinary biomarkers and renal near-infrared spectroscopy predict intensive care unit outcomes after cardiac surgery in infants younger than 6 months of age.

To assess the ability of urinary acute kidney injury biomarkers and renal near-infrared spectroscopy (NIRS) to predict outcomes in infants after surgery for congenital heart disease. Urinary levels of neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), and cystatin C were measured preoperatively and postoperatively in 49 infants younger than 6 months of age. Renal NIRS was monitored for the first 24 hours after surgery. A composite poor outcome was defined as death, the need for renal replacement therapy, prolonged time to first extubation, or prolonged intensive care unit length of stay. Forty-two (86%) patients had acute kidney injury as indicated by at least Acute Kidney Injury Network/Kidney Disease: Improving Global Outcomes (AKIN/KDIGO) stage 1 criteria, and 17 (35%) patients had poor outcomes, including 3 deaths. With the exception of KIM-1, all biomarkers demonstrated significant increases within 24 hours postoperatively among patients with poor outcomes. Low levels of NGAL and IL-18 demonstrated high negative predictive values (91%) within 2 hours postoperatively. Poor outcome infants had greater cumulative time with NIRS saturations less than 50% (60 vs 1.5 minutes; P = .02) in the first 24 hours. Within the first 24 hours after cardiopulmonary bypass, infants at increased risk for poor outcomes demonstrated elevated urinary NGAL, IL-18, and cystatin C and increased time with low NIRS saturations. These findings suggest that urinary biomarkers and renal NIRS may differentiate patients with good versus poor outcomes in the early postoperative period, which could assist clinicians when counseling families and inform the development of future clinical trials.

Hazle MA ，Gajarski RJ ，Aiyagari R ，Yu S ，Abraham A ，Donohue J ，Blatt NB ... -  《-》

Serum Cystatin C as an Early Marker of Neutrophil Gelatinase-associated Lipocalin-positive Acute Kidney Injury Resulting from Cardiopulmonary Bypass in Infants with Congenital Heart Disease.

Acute kidney injury (AKI) is a common complication resulting from cardiopulmonary bypass in infants. Urinary neutrophil gelatinase-associated lipocalin (NGAL) is a sensitive and specific marker of such injury. In this study, we compared the performance of serum cystatin C (Cys C) and serum creatinine (Cr) as early markers of renal dysfunction in infants undergoing cardiac surgery under bypass. The study was designed as a prospective observational study. The study was conducted in the cardiac intensive care unit (ICU) of a tertiary, academic children's hospital in the United States. Infants (age <1 year) undergoing cardiac surgery under cardiopulmonary bypass were included in the study. Acute kidney injury was defined based on postoperative urinary NGAL. A total of 17 infants were included in the study, and five of them developed AKI. Serum Cys C and Cr levels were measured postoperatively on days 1, 2, and 3, and compared with baseline levels. On postoperative day 2, infants with AKI showed significant change from baseline in serum Cys C levels compared with non-AKI infants (28% vs. -9%, P = .03). The two groups did not show significant differences with respect to rise in serum Cr on any of the 3 postoperative days. Serum Cr on days 1 and 2 showed nonspecific increases in both AKI and non-AKI groups. The area under the receiver operating characteristic curve for day 2 Cys C was 0.87 (95% CI 0.67-1.00) in recognizing NGAL-positive AKI. Postoperative serum Cys C appears to be a more specific and sensitive biomarker for NGAL-positive AKI resulting from cardiopulmonary bypass surgery in infants undergoing cardiac surgery.

Herbert C ，Patel M ，Nugent A ，Dimas VV ，Guleserian KJ ，Quigley R ，Modem V ... -  《-》

Temporal relationship and predictive value of urinary acute kidney injury biomarkers after pediatric cardiopulmonary bypass.

We investigated the temporal pattern and predictive value (alone and in combination) of 4 urinary biomarkers (neutrophil gelatinase-associated lipocalin [NGAL], interleukin [IL]-18, liver fatty acid-binding protein [L-FABP], and kidney injury molecule [KIM]-1) for cardiac surgery-associated acute kidney injury (AKI). Serum creatinine (S(Cr)) is a delayed marker for AKI after cardiopulmonary bypass (CPB). Rapidly detectable AKI biomarkers could allow early intervention and improve outcomes. Data from 220 pediatric patients were analyzed. Urine samples were obtained before and at intervals after CPB initiation. AKI was defined as a ≥50% increase in S(Cr) from baseline within 48 h after CPB. The temporal pattern of biomarker elevation was established, and biomarker elevations were correlated with AKI severity and clinical outcomes. Biomarker predictive abilities were evaluated by area under the curve (AUC), net reclassification improvement, and integrated discrimination improvement. AKI occurred in 27% of patients. Urine NGAL significantly increased in AKI patients at 2 h after CPB initiation. IL-18 and L-FABP increased at 6 h, and KIM-1 increased at 12 h. Biomarker elevations were correlated with AKI severity and clinical outcomes and improved AKI prediction above a clinical model. At 2 h, addition of NGAL increased the AUC from 0.74 to 0.85 (p < 0.0001). At 6 h, NGAL, IL-18, and L-FABP each improved the AUC from 0.72 to 0.91, 0.84, and 0.77, respectively (all p < 0.05). The added predictive ability of the biomarkers was supported by net reclassification improvement and integrated discrimination improvement. Biomarker combinations further improved AKI prediction. Urine NGAL, IL-18, L-FABP, and KIM-1 are sequential predictive biomarkers for AKI and are correlated with disease severity and clinical outcomes after pediatric CPB. These biomarkers, particularly in combination, may help establish the timing of injury and allow earlier intervention in AKI.

Krawczeski CD ，Goldstein SL ，Woo JG ，Wang Y ，Piyaphanee N ，Ma Q ，Bennett M ，Devarajan P ... -  《-》

Urinary interleukin-18 and urinary neutrophil gelatinase-associated lipocalin predict acute kidney injury following pulmonary valve replacement prior to serum creatinine.

It is becoming increasingly recognized that manifestations of congenital heart disease (CHD) extend beyond the cardiovascular system. The factors contributing to renal dysfunction in patients with CHD are multifactorial, with acute kidney injury (AKI) at time of cardiac surgery playing a major role. AKI is often diagnosed based on changes in serum creatinine and estimated glomerular filtration rate (eGFR). Such measurements are often late and imprecise. Recent data indicate that urinary biomarkers interleukin-18 (IL-18) and neutrophil gelatinase-associated lipocalin (NGAL) are earlier markers of AKI. We sought to determine the efficacy of urinary IL-18 and NGAL for detecting early AKI in patients undergoing surgical pulmonary valve replacement (PVR). Twenty patients presenting for surgical PVR with a history of previous repair of a conotruncal anomaly were enrolled. Preoperative clinical data were measured and urine samples and serum creatinine were collected at 6, 12, 24, and 72 hours post bypass. Urine was evaluated for NGAL and IL-18. AKI was determined using the Risk, Injury, Failure, Loss and End Stage Renal Disease (RIFLE) classification system. Using the RIFLE classification system, seven patients (35%) were found to have AKI defined as a drop in the eGFR or an increase in serum creatinine. All seven patients with AKI had marked increase from preoperative baseline in urine IL-18 (sixfold) and NGAL (26-fold). Using NGAL and IL-18, AKI was detected at 6 hours postoperatively, resulting in AKI being identified 12-36 hours prior to detection by conventional methods. No preoperative predictors for AKI were identified. Both NGAL and IL-18 are early predictive biomarkers of AKI, and both increase in tandem after surgical PVR. Importantly, both rise before an increase in creatinine or a decrease in eGFR is present. Monitoring both biomarkers may allow for earlier detection and subsequent interventions to prevent AKI at time of surgery for CHD.

Buelow MW ，Dall A ，Regner K ，Weinberg C ，Bartz PJ ，Sowinski J ，Rudd N ，Katzmark L ，Tweddell JS ，Earing MG ... -  《-》

Some biomarkers of acute kidney injury are increased in pre-renal acute injury.

Nejat M ，Pickering JW ，Devarajan P ，Bonventre JV ，Edelstein CL ，Walker RJ ，Endre ZH ... -  《-》