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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoferritins / metabolism
  • Biopsy
  • Cation Transport Proteins / metabolism
  • Female
  • Heme Oxygenase-1 / metabolism
  • Humans
  • Immunohistochemistry
  • Iron / metabolism*
  • Kidney / metabolism*
  • Male
  • Prevalence
  • Renal Insufficiency, Chronic / metabolism*


  • Cation Transport Proteins
  • SLC39A14 protein, human
  • SLC39A8 protein, human
  • metal transporting protein 1
  • Apoferritins
  • Iron
  • Heme Oxygenase-1