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
Review
. 2021 Nov;16(11):1723-1729.
doi: 10.2215/CJN.15590920. Epub 2021 Apr 5.

Chronic Allograft Injury

Eric Langewisch  1 , Roslyn B Mannon  1   2
Affiliations
Review

Chronic Allograft Injury

Eric Langewisch et al. Clin J Am Soc Nephrol. 2021 Nov.

Abstract

With the incremental improvements in long-term kidney transplant survival, there is renewed focus on what causes failure of the transplanted allograft. Over the past decade, our understanding of the injuries that lead to loss of graft function over time has evolved. Chronic allograft injury includes both immune-mediated and nonimmune-mediated injuries, which may involve the organ donor, the recipient, or both. The targets of injury include the kidney tubular epithelium, the endothelium, and the glomerulus. As a response to injury, there are the expected tissue remodeling and repair processes. However, if inflammation persists, which is not uncommon in the transplant setting, the resulting maladaptive response is matrix deposition and/or fibrosis. This ultimately leads to declining graft function and, finally, failure. With our advancing knowledge of the multiple etiologies and mechanisms, enhanced by more recent cohort studies in humans, there is an opportunity to identify those at greater risk to initiate new strategies to ameliorate the process. Although the most recent studies focus on immune-mediated injuries, there is a critical need to identify both markers of injury and mechanisms of injury. In this review, we highlight the findings of recent studies, highlight the potential therapeutic targets, and identify the continued unmet need for understanding the mechanisms of late graft failure.

Keywords: allografts; chronic allograft failure; kidney transplantation series; renal fibrosis; renal injury; transplantation.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Schema of the potential sites of injury associated with late allograft failure. There may be “fixed” injury as a consequence of the donation and transplant process (“pretransplant injury”). Three target sites of injury within the kidney are shown, with defined histologic characteristics. The entities that contribute to these sites directly (solid arrows) are shown aligned to their injury at that site. There may also be “crosstalk” of disease processes between compartments (hashed arrows) as well as cumulative injury from multiple entities directly (solid arrows) or indirectly (hashed arrows). ATN, acute tubular necrosis; CNI, calcineurin inhibitor; UTI, urinary tract infection.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. OPTN/SRTR : OPTN/SRTR 2018 Annual Data Report: Introduction. Am J Transplant 20[Suppl s1]: 11–19, 2020 - PubMed
    1. Schold JD, Augustine JJ, Huml AM, O’Toole J, Sedor JR, Poggio ED: Modest rates and wide variation in timely access to repeat kidney transplantation in the United States. Am J Transplant 20: 769–778, 2020 - PMC - PubMed
    1. El-Zoghby ZM, Stegall MD, Lager DJ, Kremers WK, Amer H, Gloor JM, Cosio FG: Identifying specific causes of kidney allograft loss. Am J Transplant 9: 527–535, 2009 - PubMed
    1. Matas AJ, Leduc R, Rush D, Cecka JM, Connett J, Fieberg A, Halloran P, Hunsicker L, Cosio F, Grande J, Mannon R, Gourishankar S, Gaston R, Kasiske B: Histopathologic clusters differentiate subgroups within the nonspecific diagnoses of CAN or CR: Preliminary data from the DeKAF study. Am J Transplant 10: 315–323, 2010 - PubMed
    1. Solez K, Axelsen RA, Benediktsson H, Burdick JF, Cohen AH, Colvin RB, Croker BP, Droz D, Dunnill MS, Halloran PF, Häyry P, Jennette JC, Keown PA, Marcussen N, Mihatsch MJ, Morozumi K, Myers BD, Nast CC, Olsen S, Racusen LC, Ramos EL, Rosen S, Sachs DH, Salomon DR, Sanfilippo F, Verani R, von Willebrand E, Yamaguchi Y: International standardization of criteria for the histologic diagnosis of renal allograft rejection: The Banff working classification of kidney transplant pathology. Kidney Int 44: 411–422, 1993 - PubMed

Publication types

MeSH terms

Substances