Kidney Biomarkers of Injury and Repair as Predictors of Contrast-Associated AKI: A Substudy of the PRESERVE Trial.

Abstract

RATIONALE & OBJECTIVE:

The PRESERVE trial used a 2 × 2 factorial design to compare intravenous saline solution with intravenous sodium bicarbonate solution and oral N-acetylcysteine with placebo for the prevention of 90-day major adverse kidney events and death (MAKE-D) and contrast-associated acute kidney injury (CA-AKI) among patients with chronic kidney disease undergoing angiography. In this ancillary study, we evaluated the predictive capacities of preangiography injury and repair proteins in urine and plasma for MAKE-D, CA-AKI, and their impact on trial design.

STUDY DESIGN:

Longitudinal analysis.

SETTING & PARTICIPANTS:

A subset of participants from the PRESERVE trial.

EXPOSURES:

Injury (KIM-1, NGAL, and IL-18) and repair (MCP-1, UMOD, and YKL-40) proteins in urine and plasma 1 to 2 hours preangiography.

OUTCOMES:

MAKE-D and CA-AKI.

ANALYTICAL APPROACH:

We analyzed the associations of preangiography biomarkers with MAKE-D and with CA-AKI. We evaluated whether the biomarker levels could enrich the MAKE-D event rate and improve future clinical trial efficiency through an online biomarker prognostic enrichment tool available at prognosticenrichment.com.

RESULTS:

We measured plasma biomarkers in 916 participants and urine biomarkers in 797 participants. After adjusting for urinary albumin-creatinine ratio and baseline estimated glomerular filtration rate, preangiography levels of 4 plasma (KIM-1, NGAL, UMOD, and YKL-40) and 3 urine (NGAL, IL-18, and YKL-40) biomarkers were associated with MAKE-D. Only plasma KIM-1 level was significantly associated with CA-AKI after adjustment. Biomarker levels provided modest discriminatory capacity for MAKE-D. Screening patients using the 50th percentile of preangiography plasma KIM-1 or YKL-40 levels would have reduced the required sample size by 30% (∼2,000 participants).

LIMITATIONS:

Evaluation of prognostic enrichment does not account for changing trial costs, time needed to screen patients, or loss to follow-up. Most participants were male, limiting the generalizability of our findings.

CONCLUSIONS:

Preangiography levels of injury and repair biomarkers modestly predict the development of MAKE-D and can be used to improve the efficiency of future CA-AKI trials.

• Authors: Chirag R Parikh, Caroline Liu, Maria K Mor, Paul M Palevsky, James S Kaufman, Heather Thiessen Philbrook, Steven D Weisbord
• Journal: American journal of kidney diseases : the official journal of the National Kidney Foundation (Am J Kidney Dis) Vol. 75 Issue 2 Pg. 187-194 (02 2020) ISSN: 1523-6838 [Electronic] United States
• PMID: 31547939 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2019 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Chemical References

• Acute-Phase Proteins
• Biomarkers
• Contrast Media
• Cytokines
• Free Radical Scavengers
• Sodium Bicarbonate
• Acetylcysteine

Topics

• Acetylcysteine (administration & dosage)
• Acute Kidney Injury (chemically induced, drug therapy, metabolism)
• Acute-Phase Proteins (metabolism)
• Administration, Oral
• Aged
• Angiography (adverse effects)
• Biomarkers (blood, urine)
• Contrast Media (adverse effects)
• Cytokines (metabolism)
• Female
• Follow-Up Studies
• Free Radical Scavengers (administration & dosage)
• Glomerular Filtration Rate
• Humans
• Infusions, Intravenous
• Kidney Function Tests
• Male
• Prognosis
• Sodium Bicarbonate (administration & dosage)