Contrast-induced acute kidney injury (CIAKI) is a common form of iatrogenic renal disease that is associated with serious, adverse, short- and long-term outcomes. While certain risk factors for CIAKI (e.g., chronic kidney disease, heart failure) are well known, our current capacity to accurately predict which patients are going to develop CIAKI based on these factors is limited. This results in the need to implement resource-intensive preventive care on a widespread basis, rather than in the sub-group of patients at greatest risk. Furthermore, the clinical diagnosis of CIAKI, which is based on small increments in serum creatinine (SCr), is delayed by up to 2-5 days following contrast administration because elevations in SCr reflect the functional effects of renal injury rather than tubular cell damage itself. Identifying serum and/or urine biomarkers that effectively stratify patients'risk fr CIAKI and diagnose its incipient stages could help concentrate the use of preventive care in those patients most likely to derive benefit and facilitate the provision of supportive care early after renal injury in order to mitigate further tubular damage and attenuate the risk for serious, adverse, longer-term outcomes. Our group has been funded by the Department of Veterans Affairs to conduct a multicenter, randomized, clinical trial of 7,680 high-risk patients with chronc kidney disease undergoing angiography to compare the effectiveness of intravenous (IV) isotonic sodium bicarbonate with IV isotonic sodium chloride and oral N- acetylcysteine with oral placebo for the prevention of serious adverse outcomes (i.e., death, need for dialysis, persistent decline in kidney function at 90 days) associated with CIAKI. We propose to leverage the substantial resources committed to this large trial to establish a biorepository of blood and urine samples collected from study participants. This biorepository, which will be available as a common-use resource for future investigation of putative and yet-to-be identified biomarkers of CIAKI, will be used for the current proposal to address the following specific aims:
Specific aim 1 : To assess whether serum and/or urine biomarkers measured prior to angiography are able to stratify the risk of developing: a) CIAKI and;b) serious, adverse, longer-term outcomes (90-day death, need for dialysis, persistent renal injury).
Specific aim 2 : To assess whether serum and/or urine biomarkers measured 4 hours following angiography: a) permit the early diagnosis of CIAKI and;b) are able to stratify the risk of developing serious, adverse, longer-term outcomes (90-day death, need for dialysis, persistent renal injury) Specific aim 3: To examine the effect of the clinical trial interventions (i.e., IV isotonic sodium bicarbonate and oral N-acetylcysteine) on serum and urine biomarkers 4 hours following angiography and their capacity to predict the development of: a) CIAKI and;b) serious, adverse, longer-term outcomes

Public Health Relevance

This study seeks to collect and analyze blood and urine markers for their capacity to predict the development of and diagnose the very early stages of acute kidney injury caused by contrast dye administered during angiographic procedures. The study also aims to assess the capacity for blood and urine markers to predict which patients who develop acute kidney injury following angiography are likely to develop serious longer-term complications, including death, need for dialysis, and progressive deterioration in kidney function. By assessing the capacity for blood and urine markers to help identify patients'risk for diagnose, and predict risk for longer-term complications of acute kidney injury, the proposed research will help inform the use of appropriate and cost-effective care to prevent this form of kidney injury and facilitate the evaluation of interventions to treat the early stages of this condition. Additionally, the samples collected as part of this study will be available to other researchers to investigate how new, currently unknown blood and urine markers may help improve the prevention and treatment of this form of acute kidney injury.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Special Emphasis Panel (ZDK1-GRB-G (J3))
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Kimmel, Paul
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University of Pittsburgh
Internal Medicine/Medicine
Schools of Medicine
United States
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