? 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 ? ?
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