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Kidney Week

Abstract: TH-PO348

Associations of Biomarkers of Angiogenesis with AKI and Mortality Post-Cardiac Surgery

Session Information

Category: Acute Kidney Injury

  • 002 AKI: Repair and Regeneration

Authors

  • Mansour, Sherry, Yale School of Medicine, New Haven, Connecticut, United States
  • Zhang, William R., UCSF School of Medicine, San Francisco, California, United States
  • Moledina, Dennis G., Yale School of Medicine, New Haven, Connecticut, United States
  • Coca, Steven G., Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Jia, Yaqi, Yale University, New Haven, Connecticut, United States
  • Thiessen Philbrook, Heather, Yale University, New Haven, Connecticut, United States
  • Koyner, Jay L., University of Chicago, Chicago, Illinois, United States
  • Shlipak, Michael, San Francisco VA Medical Center, San Francisco, California, United States
  • Wilson, Francis Perry, Yale School of Medicine, New Haven, Connecticut, United States
  • Garg, Amit X., London Health Sciences Centre, London, Ontario, Canada
  • Parikh, Chirag R., Yale University and VAMC, New Haven, Connecticut, United States
Background

Angiogenesis is a process of new blood vessel formation after renal injury. We hypothesize that unimpeded angiogenesis following acute kidney injury (AKI) leads to maladaptive repair resulting in poor long-term outcomes.

Methods

We tested the association of a panel of angiogenesis biomarkers with AKI and 1-year mortality in 1444 adult participants who underwent cardiac surgery from the TRIBE-AKI cohort. Using Mesoscale Discovery multiplex assay, we measured adaptive repair biomarkers, placental growth factor (PlGF) and vascular endothelial growth factor (VEGF), and maladaptive repair biomarker VEGF receptor 1 (VEGFR1) from plasma samples collected before (preoperative) and 0-6 hours after (postoperative) surgery. We defined AKI using AKIN stage 1 criteria, and evaluated 1-year all-cause mortality.

Results

A total of 492 developed AKI and at one year 81 died. Among the preoperative biomarkers, VEGF was independently associated with higher odds of AKI OR 1.19 (95% CI: 1.02, 1.39) but none of the preoperative biomarkers were associated with mortality.
Each log increase of postoperative PlGF and VEGF was independently associated with lower odds of AKI, whereas each log increase of postoperative VEGFR1 had higher odds of AKI (Table). Each log increase of postoperative PlGF and VEGF was also independently associated with 44% and 20% lower odds of one-year mortality, respectively, whereas each log increase of postoperative VEGFR1 had a 2-fold increase in odds of mortality (Table). There was no interaction between angiogenesis biomarkers and mortality by AKI status. Preoperative and postoperative biomarkers were weakly correlated.

Conclusion

Although there was a slight increase in odds of AKI with higher preoperative VEGF, higher postoperative levels of adaptive repair biomarkers PlGF and VEGF were significantly associated with improved renal outcomes and reduced mortality whereas higher postoperative levels of maladaptive repair biomarkers VEGFR1 were associated with worse renal outcomes and higher mortality.

Postoperative BiomarkersAdjusted odds ratio for each log increase in biomarker (95% Confidence Interval)
 AKI*1-year all-cause mortality^
Adaptive Repair
PlGF
VEGF

Maladaptive Repair
VEGFR1
-
0.69 (0.55, 0.87)
0.89 (0.82, 0.98)

-
1.56 (1.31, 1.87)
-
0.56 (0.38, 0.83)
0.80 (0.66, 0.96)

-
1.84 (1.28, 2.65)

*Adjusted for 13 clinical variables + pre-operative biomarker concentration. ^Above + change in serum creatinine from baseline to peak post-operative