Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Mar 19;6(7):1176-1187.
doi: 10.34067/KID.0000000773.

Kidney Allograft Rejection as an Independent Nontraditional Risk Factor for Post-Transplant Cardiovascular Events

Peemai Amornkanjanawat  1 , Stephen J Kerr  2   3   4 , Thunyatorn Wuttiputhanun  1   5   6 , Natavudh Townamchai  1   5   6   7 , Asada Leelahavanichkul  8   9 , Pichaya Tantiyavarong  10 , Kearkiat Praditpornsilpa  1 , Somchai Eiam-Ong  1 , Yingyos Avihingsanon  1   5   6   7 , Suwasin Udomkarnjananun  1   5   6   7   8
Affiliations

Kidney Allograft Rejection as an Independent Nontraditional Risk Factor for Post-Transplant Cardiovascular Events

Peemai Amornkanjanawat et al. Kidney360. .

Abstract

Key Points:

  1. Kidney allograft rejection is an independent risk factor for post-transplant cardiovascular events (CVEs), regardless of kidney allograft function.

  2. Time-updated post-transplant variables were more associated with post-kidney transplantation CVEs than using the pretransplant variables only.

  3. Proper screening protocol for high-risk recipients may be necessary to reduce the incidence of post-kidney transplantation CVEs.

Background: Cardiovascular death is the leading cause of mortality in kidney transplant recipients (KTRs). Although risk factors for post-transplant cardiovascular events (CVEs) have been established, previous studies primarily focused on factors at the time of transplantation without integrating post-transplant factors into the analyses. In addition, most studies were conducted in a mixed population of cyclosporine A and tacrolimus-based immunosuppression, which have different metabolic effects. This study aims to evaluate factors for post-transplant CVEs, including both pretransplant and post-transplant variables, specifically in a population of KTRs receiving tacrolimus-based immunosuppression.

Methods: Competing risk regression was performed modeling participant demographics, transplant characteristics, and post-transplant time-updated variables. The primary outcome was the composite of post-transplant CVEs, which included myocardial infarction, heart failure, ischemic stroke, peripheral arterial disease, and cardiovascular death.

Results: The incidence of post-transplant CVEs was 15.88 per 1000 patient-years among 553 KTRs included in the study. Key factors significantly associated with post-transplant CVEs included recipient age, diabetes mellitus status, post-transplant hemoglobin A1c, 24-hour urine creatinine clearance, post-transplant serum calcium, and rejection. KTRs with a history of T-cell–mediated rejection or antibody-mediated rejection were at a three-fold (95% confidence interval, 1.22 to 7.37; P value 0.016) and 3.38-fold (95% confidence interval, 1.13 to 10.09; P value 0.029) higher risk for post-transplant CVEs, respectively. Compared with models using pretransplant factors alone, models that included both pretransplant and post-transplant variables demonstrated significantly higher prediction performance.

Conclusions: Allograft rejections significantly increased the risk of post-transplant CVEs. Surveillance protocols for post-transplant CVEs should include KTRs with a history of allograft rejection, in addition to the traditional high-risk groups.

Keywords: acute allograft rejection; acute rejection; cardiovascular events; heart failure; kidney transplantation; transplant outcomes.

PubMed Disclaimer

Conflict of interest statement

Disclosure forms, as provided by each author, are available with the online version of the article at http://links.lww.com/KN9/A968.

Figures

None
Graphical abstract
Figure 1
Figure 1
Study flow diagram. MPA, mycophenolic acid.
Figure 2
Figure 2
Cumulative incidence function for composite of post-transplant CVEs (ischemic heart disease, heart failure, peripheral vascular disease, ischemic stroke, and cardiovascular death) based on of kidney allograft rejection status. ABMR, antibody-mediated rejection; CVE, cardiovascular event; TCMR, T-cell–mediated rejection.
Figure 3
Figure 3
Cumulative incidence function according to the simplified risk score on post-transplant CVEs.
See this image and copyright information in PMC

References

    1. Khou V De La Mata NL Kelly PJ, et al. Epidemiology of cardiovascular death in kidney failure: an Australian and New Zealand cohort study using data linkage. Nephrology (Carlton). 2022;27(5):430–440. doi: 10.1111/nep.14020 - DOI - PMC - PubMed
    1. Tonelli M Wiebe N Knoll G, et al. Systematic review: kidney transplantation compared with dialysis in clinically relevant outcomes. Am J Transplant. 2011;11(10):2093–2109. doi: 10.1111/j.1600-6143.2011.03686.x - DOI - PubMed
    1. Foley RN, Parfrey PS, Sarnak MJ. Clinical epidemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis. 1998;32(5 suppl 3):S112–S119. doi: 10.1053/ajkd.1998.v32.pm9820470 - DOI - PubMed
    1. Kasiske BL, Chakkera HA, Roel J. Explained and unexplained ischemic heart disease risk after renal transplantation. J Am Soc Nephrol. 2000;11(9):1735–1743. doi: 10.1681/ASN.V1191735 - DOI - PubMed
    1. Birdwell KA, Park M. Post-transplant cardiovascular disease. Clin J Am Soc Nephrol. 2021;16(12):1878–1889. doi: 10.2215/CJN.00520121 - DOI - PMC - PubMed

LinkOut - more resources