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.

Public Health Relevance

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

Agency
National Institute of Health (NIH)
Type
Specialized Center (P50)
Project #
5P50DK096418-03
Application #
8731223
Study Section
Special Emphasis Panel (ZDK1)
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2014
Total Cost
Indirect Cost
City
Cincinnati
State
OH
Country
United States
Zip Code
45229
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Haase-Fielitz, Anja; Haase, Michael; Devarajan, Prasad (2014) Neutrophil gelatinase-associated lipocalin as a biomarker of acute kidney injury: a critical evaluation of current status. Ann Clin Biochem 51:335-51
Wang, Zhu; Ma, Shuangge; Zappitelli, Michael et al. (2014) Penalized count data regression with application to hospital stay after pediatric cardiac surgery. Stat Methods Med Res :
Jotwani, Vasantha; Scherzer, Rebecca; Abraham, Alison et al. (2014) Does HIV infection promote early kidney injury in women? Antivir Ther 19:79-87
Lennon, Michael; Devarajan, Prasad (2014) In memoriam of Clark Darwin West, MD July 4, 1918-January 11, 2014. Pediatr Nephrol 29:1293-4
Devarajan, Prasad (2014) NGAL for the detection of acute kidney injury in the emergency room. Biomark Med 8:217-9
Riley, Alyssa A; Jefferies, John L; Nelson, David P et al. (2014) Peritoneal dialysis does not adversely affect kidney function recovery after congenital heart surgery. Int J Artif Organs 37:39-47
Peralta, Ca; Scherzer, R; Grunfeld, C et al. (2014) Urinary biomarkers of kidney injury are associated with all-cause mortality in the Women's Interagency HIV Study (WIHS). HIV Med 15:291-300
Devarajan, Prasad (2013) Pediatric Acute Kidney Injury: Different From Acute Renal Failure But How And Why. Curr Pediatr Rep 1:34-40
Bagshaw, Sean M; Bennett, Michael; Devarajan, Prasad et al. (2013) Urine biochemistry in septic and non-septic acute kidney injury: a prospective observational study. J Crit Care 28:371-8

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