The Translational Research Investigating Biomarker Endpoints (TRIBE) consortium is dedicated to enhancing the safety and outcomes in patients undergoing cardiac surgery by reducing the incidence and complications of acute kidney injury (AKI). In the prior two grant cycles, we enrolled 2200 adults and children undergoing cardiac surgery, collected peri- operative blood and urine samples, and measured novel biomarkers representing kidney injury, cardiac injury and inflammatory pathways in order to determine their association with AKI and three year mortality. In this competitive renewal, we will assess the utility of additional peri-operative biomarkers in blood and urine that represent repair, fibrosis and inflammation. With the existing and new biomarkers available in this cohort, we will create multi-marker panels to detect and quantify the spectrum of kidney injury. These will be included in the prediction models for long term events that will be built using validated, emerging and innovative statistical methods. The availability of reliable peri-operative clinical models for shot and long-term outcomes will assist in clinical decision-making and inform future biomarker-guided clinical trials. In adults, the risk prediction models will focus on recurrent cardiovasculr events and longer term mortality. In children, this project will serve as a foundational epidemiological study to be conducted as the first cohort to potentially link clinical AKI and kidney injury biomarkers with the future development of hypertension and CKD. We will also collaborate with other independent NIH sponsored AKI cohorts to validate the biomarker panels derived in the adult and pediatric cohorts. Our primary research aims are:
Aim 1 : To develop a peri-operative biomarker panel to optimally categorize and quantify the impact of cardiac surgery on the kidney and long-term health outcomes in adults.
Aim 2 : To determine whether clinical AKI and kidney injury defined by peri-operative biomarkers have long-term adverse effects among children after cardiac surgery.
Aim 3 : To validate multiplex biomarker panels of kidney injury markers in independent cohorts of adults and children.
Acute Kidney Injury (AKI) is a common complication in adults and children undergoing cardiac surgery with significant impact on long term morbidity and mortality. In this proposal, we will evaluate novel urinary and blood biomarkers and their relationship to AKI and long term complications such as hypertension and chronic kidney disease in children, and recurrent cardiovascular events and mortality in adults. We plan to develop a panel of biomarkers to predict these long term outcomes, which will assist in the design of trials to reduce the burden of AKI and ultimately assist with clinical care.
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| Greenberg, Jason H; Kakajiwala, Aadil; Parikh, Chirag R et al. (2018) Emerging biomarkers of chronic kidney disease in children. Pediatr Nephrol 33:925-933 |
| Greenberg, Jason H; Zappitelli, Michael; Jia, Yaqi et al. (2018) Biomarkers of AKI Progression after Pediatric Cardiac Surgery. J Am Soc Nephrol 29:1549-1556 |
| Meisner, Allison; Kerr, Kathleen F; Thiessen-Philbrook, Heather et al. (2018) Development of biomarker combinations for postoperative acute kidney injury via Bayesian model selection in a multicenter cohort study. Biomark Res 6:3 |
| Wilson, F Perry; Parikh, Chirag R (2018) Translational Methods in Nephrology: Individual Treatment Effect Modeling. J Am Soc Nephrol 29:2615-2618 |
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| Greenberg, Jason H; Devarajan, Prasad; Thiessen-Philbrook, Heather R et al. (2018) Kidney injury biomarkers 5 years after AKI due to pediatric cardiac surgery. Pediatr Nephrol 33:1069-1077 |
| Moledina, Dennis G; Parikh, Chirag R (2018) Phenotyping of Acute Kidney Injury: Beyond Serum Creatinine. Semin Nephrol 38:3-11 |
| Kerr, Kathleen F; Janes, Holly (2017) First things first: risk model performance metrics should reflect the clinical application. Stat Med 36:4503-4508 |
| de Fontnouvelle, Christina A; Greenberg, Jason H; Thiessen-Philbrook, Heather R et al. (2017) Interleukin-8 and Tumor Necrosis Factor Predict Acute Kidney Injury After Pediatric Cardiac Surgery. Ann Thorac Surg 104:2072-2079 |
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