Kidney Week

Abstract: TH-PO1159

Kidney Injury Biomarkers and Contrast-Associated AKI: A Substudy of the PRESERVE Trial

Session Information

• Late-Breaking Clinical Trials Posters
  October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• No subcategory defined

Authors

• Parikh, Chirag R., Johns Hopkins University , Baltimore, Maryland, United States

Chirag R. Parikh,

• Palevsky, Paul M., University of Pittsburgh/VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, United States

Paul M. Palevsky,

• Kaufman, James S., VA New York Harbor Healthcare System, New York, New York, United States

James S. Kaufman,

• Thiessen Philbrook, Heather, Johns Hopkins University , Baltimore, Maryland, United States

Heather Thiessen Philbrook,

• Weisbord, Steven D., University of Pittsburgh/VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, United States

Steven D. Weisbord,

Group or Team Name

• PRESERVE Trial Study Group

Background

The utility of novel biomarkers in contrast-associated AKI (CA-AKI) is unknown. Among PRESERVE trial participants, we evaluated novel proteins of kidney injury and repair to risk stratify post-angiography CA-AKI and 90-day major adverse kidney events and death (MAKE-D); predict pharmacodynamic response to the trial interventions (bicarbonate and acetylcysteine) and; inform clinical trial design.

Methods

We collected plasma and urine 1-2 hours pre- and 2-4 hours post-angiography and measured injury (KIM-1, NGAL, IL-18) and repair (MCP-1, UMOD, and YKL-40) proteins at both time points. We analyzed the association of pre-, post-, and delta (Δ) biomarker levels with 90-day MAKE-D (dialysis, persistent kidney impairment, death) and with CA-AKI. We also evaluated the association of the trial interventions with Δ biomarker levels, and examined whether biomarkers could enrich the primary MAKE-D event rate to improve trial efficiency.

Results

Among 860 PRESERVE participants, pre-angiography levels of four plasma and four urine biomarkers were significantly associated with MAKE-D (Table). Absolute and relative Δ in biomarker levels were modest and were not associated with MAKE-D or CA-AKI. None of the biomarkers demonstrated significant changes with trial interventions. Incorporating the 50^th percentile pre-angiography plasma KIM-1 or YKL-40 value into patient screening would have enriched the MAKE-D event rate and reduced the required sample size by ~2000 (30%) participants (prognosticenrichment.com).

Conclusion

Pre-angiography levels of injury and repair biomarkers predict the development of post-angiography MAKE-D outcomes and could improve efficiency of future CA-AKI trials. Changes in biomarker levels did not predict MAKE-D, CA-AKI, or pharmacodynamic response to the trial interventions. The modest change in biomarker levels following angiography suggests that most cases of CA-AKI reflect hemodynamic effects rather than intrinsic kidney damage.

Preagiography biomarker levels (pg/ml) and their association with primary outcome

Funding

• Other NIH Support