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
. 2020 Dec;33(6):1201-1211.
doi: 10.1007/s40620-020-00726-z. Epub 2020 Mar 19.

Kidney allograft fibrosis: what we learned from latest translational research studies

Simona Granata #  1 , Claudia Benedetti #  1 , Giovanni Gambaro  1 , Gianluigi Zaza  2
Affiliations
Review

Kidney allograft fibrosis: what we learned from latest translational research studies

Simona Granata et al. J Nephrol. 2020 Dec.

Abstract

To add new molecular and pathogenetic insights into the biological machinery associated to kidney allograft fibrosis is a major research target in nephrology and organ transplant translational medicine. Interstitial fibrosis associated to tubular atrophy (IF/TA) is, in fact, an inevitable and progressive process that occurs in almost every type of chronic allograft injury (particularly in grafts from expanded criteria donors) characterized by profound remodeling and excessive production/deposition of fibrillar extracellular matrix (ECM) with a great clinical impact. IF/TA is detectable in more than 50% of kidney allografts at 2 years. However, although well studied, the complete cellular/biological network associated with IF/TA is only partially evaluated. In the last few years, then, thanks to the introduction of new biomolecular technologies, inflammation in scarred/fibrotic parenchyma areas (recently acknowledged by the BANFF classification) has been recognized as a pivotal element able to accelerate the onset and development of the allograft chronic damage. Therefore, in this review, we focused on some new pathogenetic elements involved in graft fibrosis (including epithelial/endothelial to mesenchymal transition, oxidative stress, activation of Wnt and Hedgehog signaling pathways, fatty acids oxidation and cellular senescence) that, in our opinion, could become in future good candidates as potential biomarkers and therapeutic targets.

Keywords: Cellular senescence; Fatty acids oxidation; Interstitial fibrosis and tubular atrophy; Kidney fibrosis; Wnt pathway; hedgehog signaling pathways.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Liu Y (2006) Renal fibrosis: new insights into the pathogenesis and therapeutics. Kidney Int 69(2):213–217 - PubMed
    1. Melk A, Schmidt BM, Vongwiwatana A, Rayner DC, Halloran PF (2005) Increased expression of senescence-associated cell cycle inhibitor p16INK4a in deteriorating renal transplants and diseased native kidney. Am J Transplant 5(6):1375–1382 - PubMed
    1. Dimény E, Wahlberg J, Larsson E, Fellström B (1995) Can histopathological findings in early renal allograft biopsies identify patients at risk for chronic vascular rejection? Clin Transplant 9(2):79–84 - PubMed
    1. Isoniemi HM, Krogerus L, von Willebrand E, Taskinen E, Ahonen J, Häyry P (1992) Histopathological findings in well-functioning, long-term renal allografts. Kidney Int 41(1):155–160 - PubMed
    1. Serón D, Moreso F, Ramón JM et al (2000) Protocol renal allograft biopsies and the design of clinical trials aimed to prevent or treat chronic allograft nephropathy. Transplantation 69(9):1849–1855 - PubMed

Substances

LinkOut - more resources