Acute Kidney Injury (AKI) is a common clinical problem defined by an abrupt (<48 hour) increase in serum creatinine (SCr) resulting from an injury or insult causing a functional or structural change in the kidney. Despite significant advancements in the care of the critically ill child, mortality rates in children who develop AKI have not improved. Using genomic and proteomic technologies, we identified neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker that is produced in high levels in the kidney very early after kidney injury. We have developed three aims for these complementary studies: NGAL directed therapy to prevent AKI, NGAL directed therapy to optimize support for patients who develop AKI and biomarker/proteomic profiling to predict or detect CKD development early. Accordingly the specific aims of this proposal are:
Aim 1. Prevent AKI - this aim will determine if the administration of fenoldopam to children at risk for AKI, based upon plasma NGAL point of care testing, will prevent the occurrence of AKI following CPB. AKI will be determined based on the modified pediatric RIFLE (pRIFLE) criteria. Using pRIFLE, AKI will be defined as an estimated creatinine clearance decrease by ? 25% from preoperative baseline level or urine output <0.5 ml/kg/hr for 6 hours within 48h of surgery.
Aim 2. Prevent acute complications of AKI - this aim will determine if persistently elevated NGAL can predict which critically ill children will ultimately develop significant (>10%) positive ICU fluid accumulation for more than 24 hours and thereby optimize dialysis initiation.
Aim 3 : Predict long term consequences of AKI - this aim will assess urinary proteomic profiles for discovery of novel biomarkers to predict the AKI recovery and/or transition of AKI to CKD. The multidisciplinary team of investigators, including pediatric nephrologists, intensivists, cardiologists, and biostatisticians will extensively employ the Proteomics Core (Core B) and the Biomarker Core (Core C) for the successful completion of this project.
Pediatric kidney diseases due to acute kidney injury contributes to an enormous major impact on the U.S. public health and a major financial burden. Project 1 of this Center of Excellence will utilize multiple investigators and multiple Center Cores to provide critical results of styudies aimed at preventing acute kidney injury as well as diagnosing and managing its complications to change the dismal outcome
|Magella, Bliss; Adam, Mike; Potter, Andrew S et al. (2018) Cross-platform single cell analysis of kidney development shows stromal cells express Gdnf. Dev Biol 434:36-47|
|Lang, Joshua; Katz, Ronit; Ix, Joachim H et al. (2018) Association of serum albumin levels with kidney function decline and incident chronic kidney disease in elders. Nephrol Dial Transplant 33:986-992|
|Chihanga, Tafadzwa; Ma, Qing; Nicholson, Jenna D et al. (2018) NMR spectroscopy and electron microscopy identification of metabolic and ultrastructural changes to the kidney following ischemia-reperfusion injury. Am J Physiol Renal Physiol 314:F154-F166|
|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|
|Volovelsky, Oded; Gist, Katja M; Terrell, Tara C et al. (2018) Early postoperative measurement of fibroblast growth factor 23 predicts severe acute kidney injury in infants after cardiac surgery?. Clin Nephrol 90:165-171|
|Gist, Katja M; Cooper, David S; Wrona, Julia et al. (2018) Acute Kidney Injury Biomarkers Predict an Increase in Serum Milrinone Concentration Earlier Than Serum Creatinine-Defined Acute Kidney Injury in Infants After Cardiac Surgery. Ther Drug Monit 40:186-194|
|Bennett, Michael R; Pyles, Olivia; Ma, Qing et al. (2018) Preoperative levels of urinary uromodulin predict acute kidney injury after pediatric cardiopulmonary bypass surgery. Pediatr Nephrol 33:521-526|
|Albert, Christian; Albert, Annemarie; Bellomo, Rinaldo et al. (2018) Urinary neutrophil gelatinase-associated lipocalin-guided risk assessment for major adverse kidney events after open-heart surgery. Biomark Med 12:975-985|
|Basu, Rajit K; Kaddourah, Ahmad; Goldstein, Stuart L et al. (2018) Assessment of a renal angina index for prediction of severe acute kidney injury in critically ill children: a multicentre, multinational, prospective observational study. Lancet Child Adolesc Health 2:112-120|
|Jotwani, Vasantha; Scherzer, Rebecca; Glidden, David V et al. (2018) Pre-exposure Prophylaxis With Tenofovir Disoproxil Fumarate/Emtricitabine and Kidney Tubular Dysfunction in HIV-Uninfected Individuals. J Acquir Immune Defic Syndr 78:169-174|
Showing the most recent 10 out of 124 publications