? Acute renal failure (ARF) secondary to ischemic injury remains a common and devastating problem, mainly due to the lack of early biomarkers. We have recently identified Neutrophil Gelatinase-Associated Lipocalin (NGAL) as a protein that is markedly induced in kidney tubule cells very early after ischemia, and rapidly secreted into the urine where it can be easily detected and measured.
The specific aim of this project is to evaluate NGAL as an innovative biomarker of early renal injury in two highly susceptible human populations, namely open heart surgery and kidney transplantation. The Heart Center at CCHMC performs over 300 open heart surgeries annually, with a 25-30% risk of developing ARF. In pilot studies, urinary NGAL measured within 2 hours of bypass correlated with ARF and serum creatinine peak (which occurred days later). All patients undergoing open heart surgeries will be screened. Pre-existing renal failure will be the only exclusion criterion. Serum and urine samples will be collected at regular intervals for the measurement of NGAL. Other urinary biomarkers, including urine creatinine, NAG and beta2-microglobulin will be determined for comparison with NGAL. The degree and pattern of NGAL expression will be correlated with ARF (the primary outcome variable), urine output, bypass time, changes in other biomarkers, and clinical outcomes (length of ICU and hospital stay, need for dialysis, mortality). The Kidney Transplant Centers at CCHMC and UC perform about 30 living related (short ischemia time) and 60 cadaveric kidney transplants (long and variable ischemia times) annually. In pilot studies, we have determined that urinary NGAL measured within 2 hours of kidney transplantation correlated with delayed graft function and serum creatinine peak. All patients undergoing kidney transplantation will be eligible to participate. Serum and urine samples will be collected at regular intervals for measurement of NGAL levels. Other urinary biomarkers will be determined for comparison with NGAL. The pattern of NGAL expression will be correlated with delayed graft function (the primary outcome variable), cold ischemia time, changes in other urinary biomarkers, and clinical outcomes (transplant rejection, infection, chronic allograft dysfunction). The results will provide critical validation for NGAL as an innovative early non-invasive biomarker in ischemic acute renal injury. The long-term goal is to identify novel biomarkers for the early diagnosis of human ARF, to facilitate the early institution of therapy ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21DK070163-01
Application #
6876282
Study Section
Special Emphasis Panel (ZDK1-GRB-7 (O3))
Program Officer
Wilder, Elizabeth L
Project Start
2004-09-30
Project End
2006-08-31
Budget Start
2004-09-30
Budget End
2005-08-31
Support Year
1
Fiscal Year
2004
Total Cost
$223,500
Indirect Cost
Name
Cincinnati Children's Hospital Medical Center
Department
Type
DUNS #
071284913
City
Cincinnati
State
OH
Country
United States
Zip Code
45229
Devarajan, Prasad (2011) Biomarkers for the early detection of acute kidney injury. Curr Opin Pediatr 23:194-200
Bennett, Michael R; Devarajan, Prasad (2011) Proteomic analysis of acute kidney injury: biomarkers to mechanisms. Proteomics Clin Appl 5:67-77
Devarajan, Prasad (2010) The use of targeted biomarkers for chronic kidney disease. Adv Chronic Kidney Dis 17:469-79
Devarajan, Prasad (2010) Review: neutrophil gelatinase-associated lipocalin: a troponin-like biomarker for human acute kidney injury. Nephrology (Carlton) 15:419-28
Devarajan, Prasad (2010) Neutrophil gelatinase-associated lipocalin: a promising biomarker for human acute kidney injury. Biomark Med 4:265-80
Devarajan, Prasad (2009) The strong silent type: the distal tubule to the rescue. Crit Care Med 37:2129-30
Hinze, Claas H; Suzuki, Michiko; Klein-Gitelman, Marisa et al. (2009) Neutrophil gelatinase-associated lipocalin is a predictor of the course of global and renal childhood-onset systemic lupus erythematosus disease activity. Arthritis Rheum 60:2772-81
Goldstein, Stuart L; Devarajan, Prasad (2008) Progression from acute kidney injury to chronic kidney disease: a pediatric perspective. Adv Chronic Kidney Dis 15:278-83
Bennett, Michael; Dent, Catherine L; Ma, Qing et al. (2008) Urine NGAL predicts severity of acute kidney injury after cardiac surgery: a prospective study. Clin J Am Soc Nephrol 3:665-73
Lavery, Adrian P; Meinzen-Derr, Jareen K; Anderson, Edward et al. (2008) Urinary NGAL in premature infants. Pediatr Res 64:423-8

Showing the most recent 10 out of 38 publications