Elevated Levels of Urinary Biomarkers TIMP-2 and IGFBP-7 Predict Acute Kidney Injury in Neonates after Congenital Heart Surgery

Author(s):  
Michelle Ramírez ◽  
Sujata Chakravarti ◽  
Jaclyn McKinstry ◽  
Yasir Al-qaqaa ◽  
Raj Sahulee ◽  
...  

Abstract 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.

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Michelle Ramirez ◽  
Sujata Chakravarti ◽  
Gefen Ashley ◽  
McKinstry Jaclyn ◽  
Sahulee Raj ◽  
...  

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.


2013 ◽  
Vol 24 (5) ◽  
pp. 831-839 ◽  
Author(s):  
J. Bryan Carmody ◽  
Michael D. Seckeler ◽  
Cortney R. Ballengee ◽  
Mark Conaway ◽  
K. Anitha Jayakumar ◽  
...  

AbstractObjective: Acute kidney injury is common in neonates following surgery for congenital heart disease. We conducted a retrospective analysis to determine whether neonates with smaller pre-operative renal volume were more likely to develop post-operative acute kidney injury. Design/Setting: We conducted a retrospective review of 72 neonates who underwent congenital heart surgery for any lesion other than patent ductus arteriosus at our institution from January 2007 to December 2011. Renal volume was calculated by ultrasound using the prolate ellipsoid formula. The presence and severity of post-operative acute kidney injury was determined both by measuring the peak serum creatinine in the first 7 days post-operatively and by using the Acute Kidney Injury Network scoring system. Results: Using a linear change point model, a threshold renal volume of 17 cm3 was identified. Below this threshold, there was an inverse linear relationship between renal volume and peak post-operative creatinine for all patients (p = 0.036) and the subgroup with a single morphologic right ventricle (p = 0.046). There was a non-significant trend towards more acute kidney injury using Acute Kidney Injury Network criteria in all neonates with renal volume ≤17 cm3 (p = 0.11) and in the subgroup with a single morphologic right ventricle (p = 0.17). Conclusions: Pre-operative renal volume ≤17 cm3 is associated with a higher peak post-operative creatinine and potentially greater risk for post-operative acute kidney injury for neonates undergoing congenital heart surgery. Neonates with a single right ventricle may be at higher risk.


2012 ◽  
Vol 143 (2) ◽  
pp. 368-374 ◽  
Author(s):  
Joshua J. Blinder ◽  
Stuart L. Goldstein ◽  
Vei-Vei Lee ◽  
Alixandra Baycroft ◽  
Charles D. Fraser ◽  
...  

Medicine ◽  
2017 ◽  
Vol 96 (28) ◽  
pp. e7480 ◽  
Author(s):  
Youn Yi Jo ◽  
Ji Young Kim ◽  
Ji Yeon Lee ◽  
Chang Hu Choi ◽  
Young Jin Chang ◽  
...  

2020 ◽  
Vol 49 (1) ◽  
pp. 198-198
Author(s):  
Ian Justement ◽  
Andrea Marroquin ◽  
Jaime Silva-Gburek ◽  
Andrea Ontaneda ◽  
Jeramy Roddy ◽  
...  

2019 ◽  
Vol 20 (10) ◽  
pp. 947-956 ◽  
Author(s):  
Elin M. Thorlacius ◽  
Pertti K. Suominen ◽  
Håkan Wåhlander ◽  
Juho Keski-Nisula ◽  
Maria Vistnes ◽  
...  

PEDIATRICS ◽  
2016 ◽  
Vol 137 (Supplement 3) ◽  
pp. 262A-262A
Author(s):  
Raya Safa ◽  
Sanjeev Aggarwal

2016 ◽  
Vol 27 (6) ◽  
pp. 1068-1075 ◽  
Author(s):  
David M. Kwiatkowski ◽  
Elizabeth Price ◽  
David M. Axelrod ◽  
Anitra W. Romfh ◽  
Brian S. Han ◽  
...  

AbstractBackgroundAcute kidney injury after cardiac surgery is a frequent and serious complication among children with congenital heart disease (CHD) and adults with acquired heart disease; however, the significance of kidney injury in adults after congenital heart surgery is unknown. The primary objective of this study was to determine the incidence of acute kidney injury after surgery for adult CHD. Secondary objectives included determination of risk factors and associations with clinical outcomes.MethodsThis single-centre, retrospective cohort study was performed in a quaternary cardiovascular ICU in a paediatric hospital including all consecutive patients ⩾18 years between 2010 and 2013.ResultsData from 118 patients with a median age of 29 years undergoing cardiac surgery were analysed. Using Kidney Disease: Improving Global Outcome creatinine criteria, 36% of patients developed kidney injury, with 5% being moderate to severe (stage 2/3). Among higher-complexity surgeries, incidence was 59%. Age ⩾35 years, preoperative left ventricular dysfunction, preoperative arrhythmia, longer bypass time, higher Risk Adjustment for Congenital Heart Surgery-1 category, and perioperative vancomycin use were significant risk factors for kidney injury development. In multivariable analysis, age ⩾35 years and vancomycin use were significant predictors. Those with kidney injury were more likely to have prolonged duration of mechanical ventilation and cardiovascular ICU stay in the univariable regression analysis.ConclusionsWe demonstrated that acute kidney injury is a frequent complication in adults after surgery for CHD and is associated with poor outcomes. Risk factors for development were identified but largely not modifiable. Further investigation within this cohort is necessary to better understand the problem of kidney injury.


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