Objectives: This article investigated the utility of urine biomarkers tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein-7 (IGFBP-7) in identifying acute kidney injury (AKI) in neonates after congenital heart surgery (CHS). TIMP-2 and IGFBP-7 are cell cycle arrest proteins detected in urine during periods of kidney stress/injury. Methods: We conducted a single-center, prospective study between September 2017 and May 2019 with neonates undergoing CHS requiring cardiopulmonary bypass (CPB). Urine samples were analyzed using NephroCheck prior to surgery and 6, 12, 24, and 96 hours post-CPB. All patients were evaluated using the Acute Kidney Injury Network (AKIN) criteria. Wilcoxon rank sum tests were used to compare the medians of the [TIMP-2*IGFBP-7] values in the AKIN negative and positive groups at each time point. Receiver operating characteristic curves were used to measure how well the [TIMP-2*IGFBP-7] values predict AKIN status. Results: Thirty-six patients were included. No patients met the AKIN criteria for AKI preoperatively. Postoperatively, 19 patients (53%) met the AKIN criteria for AKI diagnosis: 13 (36%) stage 1, 5 (14%) stage 2, and 1 (3%) stage 3. None required renal replacement therapy. At the 24-hour time points, patients who met the AKIN criteria for AKI had a statistically significantly higher [TIMP-2*IGFBP7] values than the patients without AKI (1.1 vs. 0.27 [ng/mL]2/1,000) at 24 hours (adj-p = 0.0019). Conclusion: AKI is a serious complication associated with adverse outcomes in patients undergoing cardiac surgery. [TIMP-2*IGFBP-7] urinary level 24 hours after CPB is a good predictor of AKI in this population.
Introduction: Acute kidney injury (AKI) is a common and serious complication in patients undergoing cardiac surgery and is associated with adverse outcomes. TIMP-2 and IGFBP-7 are cell cycle arrest proteins that are detected in urine during periods of kidney stress or injury. The NephroCheck™ system measures urine concentrations of these two biomarkers and calculates a score which has been validated in adults as a predictor of AKI. The utility of these markers in identifying AKI in neonates after congenital heart surgery (CHS) has not been determined. Hypothesis: Concentrations of TIMP-2 and IGFBP-7 as measured by the NephroCheck™ system will be elevated in neonates with AKI following CHS requiring cardiopulmonary bypass (CPB). Methods: We conducted a single center, prospective, observational study in neonates less than 31 days old undergoing CHS requiring CPB between 9/2017 and 5/2019. Urine samples were collected and analyzed using the NephroCheck™ system prior to surgery and at 6, 12, 24 and 96 hours (h) post CPB. All patients were evaluated for staging of AKI using the Acute Kidney Injury Network criteria (AKIN). Wilcoxon Rank Sum tests were used to compare the medians of the NephroCheck™ values in the AKIN negative and positive groups for each of the time points. ROC curves and AUCs with 95% CIs were used to measure how well the NephroCheck™ values predict the AKIN negative and positive status of the patients. Results: Thirty-six patients were included, 56% were male. Median age and weight were 7 days and 3.14 kg. Pre-surgically, no patients met AKI definition by AKIN criteria or by NephroCheck™ values. Post surgically, 52% of patients had AKI by AKIN criteria. All patients with AKI had elevated biomarkers. The presence of elevated biomarkers as determined by NephroCheck™ had a statistically significant association for the presence of AKI at the 6 h (p = 0.036) and 24 h (p = 0.00037) time points. Of all time points analyzed, samples obtained at 24h were best at predicting the development of AKI in the post-surgical period (AUC: 0.848). Conclusions: Elevation in urine concentration of TIMP-2 and IGFBP-7 is associated with AKI in neonates after CHS requiring CPB. Urinary biomarkers levels 24 h after CPB are good predictors of AKI in this population.
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