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. 2019 Jul 5;9:9762. doi: 10.1038/s41598-019-46114-x

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© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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RAS dysregulation after kidney transplantation. Early after KTx (<2years), a moderate ACE-mediated Ang II synthesis occurs in the graft. During the first months after transplantation, Ang-(1–7) synthesis is dominantly mediated by NEP, together with ACE -mediated Ang II synthesis from Ang I. In allografts with higher graft vintage (>12 years), a strong increase of local chymase mediated Ang II synthesis and constant NEP mediated Ang-(1–7) synthesis occurs. In patients with allografts with more than a decade of age, ACEi therapy with subsequent negative feedback and systemic renin upregulation and increased Ang I levels might trigger local chymase mediated Ang II synthesis.