This grant entitled Recombinant Erythropoietin for Protection of Infant Renal Disease (REPAIReD) is submitted in response to PAR-12-265 from the NIDDK as an Ancillary study to major ongoing clinical research study to advance areas of scientific interest within the mission of the NIDDK. This proposal will be an ancillary study of te Preterm Epo NeuroProtection Trial (PENUT), a blinded randomized placebo-controlled Phase 3 multi-center trial of Erythropoietin for Neuroprotection in Extremely Low Gestational Age (24-27 weeks) Neonates (ELGANS) funded by NINDS. The NIDDK has supported and secured the use of PENUT clinical data, blood and urine samples from 940 infants randomized to thrice weekly recombinant human erythropoietin (rHuEPO) or placebo. Infants will be followed from birth to 24-26 months corrected age. AKI occurs in approximately 30% of ELGANs. Premature infants are at twice the risk of developing albuminuria, and sustained low GFR leading to end-stage kidney disease than their term counterparts. rHuEPO not only stimulates red blood cell production, but is a promising therapy for tissue protection in the kidney, brain and other organs. This ancillary study provides an unparalleled opportunity to test our central hypothesis that rHuEPO mitigates in- hospital kidney damage in ELGANs, which ultimately decreases CKD at 24-26 months corrected age. As an ancillary study to PENUT, we propose 3 specific aims:
Aim 1 : We will determine if the degree of kidney damage and other risk factor(s) identified during the neonatal hospitalization predict CKD in ELGANS at 24-26 months corrected age.
Aim 2 : We will determine if and how rHuEPO improves in-hospital renal outcomes using serum and urine biomarkers of kidney function, injury, repair, inflammation and oxidative stress.
Aim 3 : We will determine if rHuEPO improves renal outcomes at 24-26 months. This proposal will help us predict which ELGANS develop CKD, determine if and how rHuEPO improves kidney damage, and which biomarkers are modifiable and predictive of hard clinical endpoints. Ultimately, this will improve our ability to define early kidney injury, intervene expeditiously and improve outcomes.

Public Health Relevance

In the US 50,000 infants a year are born less than 28 weeks of gestation. Though survival has improved, infants born less than 1000 grams continue to have high rates of morbidity and mortality. With more infants surviving into adulthood, subsequent CKD may pose a tremendous health and economic burden. This study offers a potential intervention to improve kidney outcomes, and by extension, reduce short and long term healthcare costs.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK103608-04
Application #
9336902
Study Section
Special Emphasis Panel (ZDK1)
Program Officer
Mendley, Susan Ruth
Project Start
2014-09-17
Project End
2019-10-31
Budget Start
2017-09-01
Budget End
2018-10-31
Support Year
4
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Seattle Children's Hospital
Department
Type
DUNS #
048682157
City
Seattle
State
WA
Country
United States
Zip Code
98101
Starr, Michelle C; Hingorani, Sangeeta R (2018) Prematurity and future kidney health: the growing risk of chronic kidney disease. Curr Opin Pediatr 30:228-235
Cornell, Timothy T; Selewski, David T; Alten, Jeffrey A et al. (2018) Acute kidney injury after out of hospital pediatric cardiac arrest. Resuscitation 131:63-68
Starr, Michelle C; Askenazi, David J; Goldstein, Stuart L et al. (2018) Impact of processing methods on urinary biomarkers analysis in neonates. Pediatr Nephrol 33:181-186
Askenazi, D J; Heung, Michael; Connor Jr, Michael J et al. (2017) Optimal Role of the Nephrologist in the Intensive Care Unit. Blood Purif 43:68-77
Askenazi, David J; Faubel, Sarah (2017) The Nephrologist Has Great Potential to Have an Important Role in the Intensive Care Unit: Reply to the Letter to the Editor of David J.R. Morgan. Blood Purif 44:269-270
Nada, Arwa; Bonachea, Elizabeth M; Askenazi, David J (2017) Acute kidney injury in the fetus and neonate. Semin Fetal Neonatal Med 22:90-97
Jetton, Jennifer G; Boohaker, Louis J; Sethi, Sidharth K et al. (2017) Incidence and outcomes of neonatal acute kidney injury (AWAKEN): a multicentre, multinational, observational cohort study. Lancet Child Adolesc Health 1:184-194
Askenazi, David (2016) Should neonates with perinatal asphyxia receive a single dose of IV theophylline to prevent acute kidney injury? Acta Paediatr 105:1125-6
Hanna, Mina H; Askenazi, David J; Selewski, David T (2016) Drug-induced acute kidney injury in neonates. Curr Opin Pediatr 28:180-7
Juul, Sandra E; Mayock, Dennis E; Comstock, Bryan A et al. (2015) Neuroprotective potential of erythropoietin in neonates; design of a randomized trial. Matern Health Neonatol Perinatol 1:27