The Role of Angiopoietins in Cardiovascular Outcomes of Kidney Transplant Recipients: An Ancillary Study from the FAVORIT.

Kanika Garg, Ugochukwu Ugwuowo, Andrew Bostom, Sherry G Mansour, Yu Yamamoto, Long Qian, Natalie Gendy, Liam Brown, Mary Kate Staunton, Nora Hernandez Garcilazo, Wassim Obeid, Lama Al-Qusairi

Journal: American journal of nephrology 2024;55(5):597-606

PMID: 38735283

Abstract

INTRODUCTION

Kidney transplant recipients (KTRs) have increased risk of cardiovascular disease (CVD) mortality. We investigated vascular biomarkers, angiopoietin-1, and angiopoietin-2 (angpt-1, -2), in CVD development in KTRs.

METHODS

This ancillary study from the FAVORIT evaluates the associations of baseline plasma angpt-1, -2 levels in CVD development (primary outcome) and graft failure (GF) and death (secondary outcomes) in 2000 deceased donor KTRs. We used Cox regression to analyze the association of biomarker quartiles with outcomes. We adjusted for demographic; CVD- and transplant-related variables; medications; urine albumin-to-creatinine ratio; and randomization status. We calculated areas under the curves (AUCs) to predict CVD or death, and GF or death by incorporating biomarkers alongside clinical variables.

RESULTS

Participants' median age was 52 IQR [45, 59] years: with 37% women and 73% identifying as white. Median time from transplantation was 3.99 IQR [1.58, 7.93] years and to CVD development was 2.54 IQR [1.11-3.80] years. Quartiles of angpt-1 were not associated with outcomes. Whereas higher levels of angpt-2 (quartile 4) were associated with about 2 times the risk of CVD, GF, and death (aHR 1.85 [1.25-2.73], p < 0.01; 2.24 [1.36-3.70)], p < 0.01; 2.30 [1.48-3.58], p < 0.01, respectively) as compared to quartile 1. Adding angiopoietins to preexisting clinical variables improved prediction of CVD or death (AUC improved from 0.70 to 0.72, p = 0.005) and GF or death (AUC improved from 0.68 to 0.70, p = 0.005). Angpt-2 may partially explain the increased risk of future CVD in KTRs. Further research is needed to assess the utility of using angiopoietins in the clinical care of KTRs.

CONCLUSION

Angpt-2 may be a useful prognostic tool for future CVD in KTRs. Combining angiopoietins with clinical markers may tailor follow-up to mitigate CVD risk.

© 2024 The Author(s). Published by S. Karger AG, Basel.

Address: Clinical and Translational Research Accelerator, New Haven, Connecticut, USA, [email protected].; Schulich School of Medicine, Western University, London, Ontario, Canada, [email protected].; Clinical and Translational Research Accelerator, New Haven, Connecticut, USA.; Section of Nephrology, Yale New Haven Hospital, New Haven, Connecticut, USA.; Johns Hopkins University, Baltimore, Maryland, USA.; Department of Family Medicine, Brown University, Providence, Rhode Island, USA.; Clinical and Translational Research Accelerator, New Haven, Connecticut, USA.; Section of Nephrology, Yale New Haven Hospital, New Haven, Connecticut, USA.
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