• Sherry G Mansour, William R Zhang, Dennis G Moledina, Steven G Coca, Yaqi Jia, Heather Thiessen-Philbrook, Eric McArthur, Kazunori Inoue, Jay L Koyner, Michael G Shlipak, F Perry Wilson, Amit X Garg, Shuta Ishibe, Chirag R Parikh, and TRIBE-AKI Consortium.
• Program of Applied Translational Research, Department of Medicine, Yale University School of Medicine, New Haven, CT; Section of Nephrology, Yale University School of Medicine, New Haven, CT.
• Am. J. Kidney Dis. 2019 Jul 1; 74 (1): 36-46.

Rationale & ObjectiveThe process of angiogenesis after kidney injury may determine recovery and long-term outcomes. We evaluated the association of angiogenesis markers with acute kidney injury (AKI) and mortality after cardiac surgery.Study DesignProspective cohort.Setting & Participants1,444 adults undergoing cardiac surgery in the TRIBE-AKI (Translational Research Investigating Biomarker Endpoints for Acute Kidney Injury) cohort.ExposuresPlasma concentrations of 2 proangiogenic markers (vascular endothelial growth factor A [VEGF] and placental growth factor [PGF]) and 1 antiangiogenic marker (soluble VEGF receptor 1 [VEGFR1]), measured pre- and postoperatively within 6 hours after surgery.OutcomesAKI, long AKI duration (≥7 days), and 1-year all-cause mortality.Analytical ApproachMultivariable logistic regression.ResultsFollowing cardiac surgery, plasma VEGF concentrations decreased 2-fold, and PGF and VEGFR1 concentrations increased 1.5- and 8-fold, respectively. There were no meaningful associations of preoperative concentrations of angiogenic markers with outcomes of AKI and mortality. Higher postoperative VEGF and PGF concentrations were independently associated with lower odds of AKI (adjusted ORs of 0.89 [95% CI, 0.82-0.98] and 0.69 [95% CI, 0.55-0.87], respectively), long AKI duration (0.65 [95% CI, 0.49-0.87] and 0.48 [95% CI, 0.28-0.82], respectively), and mortality (0.74 [95% CI, 0.62-0.89] and 0.46 [95% CI, 0.31-0.68], respectively). In contrast, higher postoperative VEGFR1 concentrations were independently associated with higher odds of AKI (1.56; 95% CI, 1.31-1.87), long AKI duration (1.75; 95% CI, 1.09-2.82), and mortality (2.28; 95% CI, 1.61-3.22).LimitationsAngiogenesis markers were not measured after hospital discharge, so we were unable to determine long-term trajectories of angiogenesis marker levels during recovery and follow-up.ConclusionsHigher levels of postoperative proangiogenic markers, VEGF and PGF, were associated with lower AKI and mortality risk, whereas higher postoperative antiangiogenic VEGFR1 levels were associated with higher risk for AKI and mortality.Copyright © 2019 National Kidney Foundation, Inc. All rights reserved.

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