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Sci Rep. 2018 Jun 19;8(1):9353. doi: 10.1038/s41598-018-27107-8.

Tubular iron deposition and iron handling proteins in human healthy kidney and chronic kidney disease.

Author information

1
Department of Laboratory Medicine, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands.
2
Department of Pathology and Medical Biology, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands.
3
Pathologie Friesland, Leeuwarden, The Netherlands.
4
Department of Pharmacology and Toxicology, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands.
5
Research Department of Pathology, UCL Cancer Institute, University College London, London, United Kingdom.
6
UCL Centre for Nephrology, Royal Free Hospital, London, United Kingdom.
7
Department of Cellular Pathology, Royal Free Hospital, London, United Kingdom.
8
Cardiovascular and Metabolic Diseases iMED ECD, AstraZeneca, Gothenburg, Sweden.
9
Department of Structural & Molecular Biology, Division of Biosciences, University College London, London, United Kingdom. k.srai@ucl.ac.uk.
10
Department of Laboratory Medicine, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands. Dorine.Swinkels@Radboudumc.nl.

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.

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