PRESERVE Sub-Study 578

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.

The PRESERVE trial (Prevention of Serious Adverse Events Following Angiography) has been funded by the Department of Veterans Affairs to conduct a multicenter, randomized, clinical trial of high-risk patients with chronic 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. Dr. Parikh served on the Executive Committee for the trial which oversaw study operations, the performance of participating medical centers, and data quality. He leveraged 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:

• 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)
• 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)
• 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

Funding Information for this Project

The PRESERVE Trial was supported by the U.S. Department of Veterans Affairs Office of Research and Development, the National Institute of Diabetes and Digestive and Kidney Diseases, and the National Health and Medical Research Council of Australia

ClinicalTrials.gov Identifier: NCT01467466

PubMed

PRESERVE Trial