eprintid: 10051349 rev_number: 24 eprint_status: archive userid: 608 dir: disk0/10/05/13/49 datestamp: 2018-07-02 13:26:23 lastmod: 2021-09-28 22:25:15 status_changed: 2018-07-02 13:26:23 type: article metadata_visibility: show creators_name: van Raaij, S creators_name: van Swelm, R creators_name: Bouman, K creators_name: Cliteur, M creators_name: van den Heuvel, M creators_name: Pertijs, J creators_name: Patel, D creators_name: Bass, P creators_name: van Goor, H creators_name: Unwin, R creators_name: Srai, SK creators_name: Swinkels, D title: Tubular iron deposition and iron handling proteins in human healthy kidney and chronic kidney disease ispublished: pub divisions: UCL divisions: B02 divisions: C08 divisions: D09 divisions: G03 divisions: C10 divisions: D19 divisions: G97 divisions: D17 note: Copyright © The Author(s) 2018. 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. Te 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/. abstract: Iron is suggested to play a detrimental role in the progression of chronic kidney disease (CKD). The kidney recycles iron back into the circulation. However, the localization of proteins relevant for physiological tubular iron handling and their potential role in CKD remain unclear. We examined associations between iron deposition, expression of iron handling proteins and tubular injury in kidney biopsies from CKD patients and healthy controls using immunohistochemistry. Iron was deposited in proximal (PT) and distal tubules (DT) in 33% of CKD biopsies, predominantly in pathologies with glomerular dysfunction, but absent in controls. In healthy kidney, PT contained proteins required for iron recycling including putative iron importers ZIP8, ZIP14, DMT1, iron storage proteins L- and H-ferritin and iron exporter ferroportin, while DT only contained ZIP8, ZIP14, and DMT1. In CKD, iron deposition associated with increased intensity of iron importers (ZIP14, ZIP8), storage proteins (L-, H-ferritin), and/or decreased ferroportin abundance. This demonstrates that tubular iron accumulation may result from increased iron uptake and/or inadequate iron export. Iron deposition associated with oxidative injury as indicated by heme oxygenase-1 abundance. In conclusion, iron deposition is relatively common in CKD, and may result from altered molecular iron handling and may contribute to renal injury. date: 2018-06 date_type: published official_url: https://doi.org/10.1038/s41598-018-27107-8 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green article_type_text: Journal Article verified: verified_manual elements_id: 1563815 doi: 10.1038/s41598-018-27107-8 pii: 10.1038/s41598-018-27107-8 lyricists_name: Bass, Paul lyricists_name: Patel, Dominic lyricists_name: Srai, Surjit lyricists_name: Unwin, Robert lyricists_id: PBASS04 lyricists_id: PATEL39 lyricists_id: SKSSR22 lyricists_id: RJUNW23 actors_name: Cuccu, Clara actors_id: CCCUC40 actors_role: owner full_text_status: public publication: Scientific Reports volume: 8 article_number: 9353 event_location: England issn: 2045-2322 citation: van Raaij, S; van Swelm, R; Bouman, K; Cliteur, M; van den Heuvel, M; Pertijs, J; Patel, D; ... Swinkels, D; + view all <#> van Raaij, S; van Swelm, R; Bouman, K; Cliteur, M; van den Heuvel, M; Pertijs, J; Patel, D; Bass, P; van Goor, H; Unwin, R; Srai, SK; Swinkels, D; - view fewer <#> (2018) Tubular iron deposition and iron handling proteins in human healthy kidney and chronic kidney disease. Scientific Reports , 8 , Article 9353. 10.1038/s41598-018-27107-8 <https://doi.org/10.1038/s41598-018-27107-8>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10051349/1/van%20Raaij1_Tubular.pdf document_url: https://discovery.ucl.ac.uk/id/eprint/10051349/8/41598_2018_27107_MOESM1_ESM.pdf