TY - JOUR
T1 - Kidney Biomarkers of Injury and Repair as Predictors of Contrast-Associated AKI
T2 - A Substudy of the PRESERVE Trial
AU - Parikh, Chirag R.
AU - Liu, Caroline
AU - Mor, Maria K.
AU - Palevsky, Paul M.
AU - Kaufman, James S.
AU - Thiessen Philbrook, Heather
AU - Weisbord, Steven D.
N1 - Funding Information:
This study was supported by the US Department of Veterans Affairs Office of Research and Development (VA CSP #578 PRESERVE Trial; PI: S.D. Weisbord, Co-PI: P.M. Palevsky), the National Institute of Diabetes and Digestive and Kidney Diseases ( R01 DK098214 Biomarker Collection and Analysis in the PRESERVE Trial Cohort; MPIs: Weisbord, Palevsky, and Parikh), and the National Health and Medical Research Council of Australia. Dr Parikh was additionally supported by the George M. O’Brien Kidney Center ( P30DK079310 ) and the National Institutes of Health ( R01HL085757 ). Funding sources had no role in the study design; data collection, analysis, or reporting; or decision to submit for publication.
Funding Information:
Chirag R. Parikh, MD, PhD, Caroline Liu, MHS, Maria K. Mor, PhD, Paul M. Palevsky, MD, James S. Kaufman, MD, Heather Thiessen Philbrook, MMath, and Steven D. Weisbord, MD, MSc. Research idea and study design: CRP, PMP, JSK, SDW; data acquisition: CRP, PMP, JSK, SDW; data analysis/interpretation: CRP, CL, MKM, HTP, PMP, JSK, SDW; statistical analysis: MKM; supervision or mentorship: CRP, SDW, HTP. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved. This study was supported by the US Department of Veterans Affairs Office of Research and Development (VA CSP #578 PRESERVE Trial; PI: S.D. Weisbord, Co-PI: P.M. Palevsky), the National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK098214 Biomarker Collection and Analysis in the PRESERVE Trial Cohort; MPIs: Weisbord, Palevsky, and Parikh), and the National Health and Medical Research Council of Australia. Dr Parikh was additionally supported by the George M. O'Brien Kidney Center (P30DK079310) and the National Institutes of Health (R01HL085757). Funding sources had no role in the study design; data collection, analysis, or reporting; or decision to submit for publication. Dr Parikh has received consulting fees from Renalytix and serves on the Data and Safety Monitoring Board of Genfit and Abbott. Dr Palevsky receives consulting fees and advisory committee fees from Durect, Novartis, and HealthSpan Dx; serves on the Data and Safety Monitoring Board of Baxter; and serves as a member of an end point adjudication committee from GE Healthcare. Dr Weisbord has received consulting fees and advisory fees from Durect and Saghmos Therapeutics. The remaining authors declare that they have no relevant financial interests. The opinions in this article are those of the authors and do not represent the views of the US government or the Department of Veterans Affairs. Parts of this study were presented in poster form at the American Society of Nephrology Kidney Week, San Diego, CA, October 23-28, 2018. Received February 7, 2019. Evaluated by 2 external peer reviewers and a statistician, with editorial input from an Acting Editor-in-Chief (Abhijit Kshirsagar, MD, MPH). Accepted in revised form June 20, 2019. The involvement of an Acting Editor-in-Chief to handle the peer-review and decision-making processes was to comply with AJKD's procedures for potential conflicts of interest for editors, described in the Information for Authors & Journal Policies.
Publisher Copyright:
© 2019 National Kidney Foundation, Inc.
PY - 2020/2
Y1 - 2020/2
N2 - 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.
AB - 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.
KW - Acute kidney injury (AKI)
KW - MAKE-D
KW - angiography
KW - clinical trial design
KW - contrast media
KW - contrast-associated acute kidney injury (CA-AKI)
KW - contrast-induced acute kidney injury (CI-AKI)
KW - enrollment criteria
KW - event rate
KW - plasma biomarkers
KW - prognostic biomarker
KW - tubular injury
KW - urinary biomarkers
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U2 - 10.1053/j.ajkd.2019.06.011
DO - 10.1053/j.ajkd.2019.06.011
M3 - Article
C2 - 31547939
AN - SCOPUS:85072278853
SN - 0272-6386
VL - 75
SP - 187
EP - 194
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
IS - 2
ER -