Disease orinjury / Findings
Human studies
Apparenthereditary haemochromatosis / ↑Urinary hemosiderin(light microscopy, modified Perl’s reaction and Nishimura’s method); ↑kidney iron(Nishimura stain); damage to the DCT, LoH and glomerulus1
-thalassaemia / ↑Kidney iron (electron microscopy, MRI); basal lamina damage (histology; electron microscopy); urinary NAG, ↑urinary malondialdehydeur1-5
Animal studies
HFE-/- mouse / ↔Urinary nonhaem iron(method not specified); ↔total kidney iron(AAS), ↑total kidney iron (colorimetric method using Prussian blue staining); ↔hemosiderin in kidney (Prussian bluestaining)6-10
Haemojuvelin-/-, hepcidin-/- mouse / ↑Urinary iron (method not specified); ↑hemosiderinin kidney(Prussian bluestaining)9
High vs. low iron diet in mice / ↑Kidney iron(AAS); iron-replete versus iron-deficient diet in mice. Not significant in HFE-/- mouse8
High iron diet in mice / ↑Urinary iron (ICP–MS);kidney damage (histology); ↓DMT-1; iron-deficient diet led to ↓UIE and↑DMT1
Hypertransfusion (mice) / ↑Urinary iron(significance not reported)(ferene-S); deferoxamine injection increases UIE13
Low iron diet in rats / ↓Non-haem iron(non-haem iron by acid hydrolysis) and bleomycin detectable iron(bleomycin assay) in kidney14
Abbreviations: ↓, decrease; ↑, increase; ↔, unchanged; AAS, atomic absorption spectrometry; DCT, distal collecting tubule; DMT-1, divalent metal transferase 1; HFE, high iron Fe (hereditary haemochromatosis gene); ICP–MS, inductively coupled plasma mass spectrometry; LoH, loop of Henle; NAGur, urinary N-acetyl-β-d-glucosaminidase; UIE, urinary iron excretion.
1.Buhl, L., Muirhead, D.E. & Prentis, P.F. Renal hemosiderosis due to thalassemia: A light and electron microscopy study with electron probe Xray microanalysis. Ultrastruc. Pathol.17, 169–183 (1993).
2.Hashemieh, M., Azarkeivan, A., Akhlaghpoor, S., Shirkavand, A. & Sheibani, K. T2-star (T2*) magnetic resonance imaging for assessment of kidney iron overload in thalassemic patients. Arch. Iran. Med.15, 91–94 (2012).
3.Aldudak, B. etal. Renal function in pediatric patients with βthalassemia major. Pediatr. Nephrol.15, 109–112 (2000).
4.Michelakakis, H. etal. Iron overload and urinary lysosomal enzyme levels in βthalassaemia major. Eur. J. Pediatr.156, 602–604 (1997).
5.Koliakos, G. etal. Urine biochemical markers of early renal dysfunction are associated with iron overload in βthalassaemia. Clin. Lab. Haematol.25, 105–109 (2003).
6.Zhou, X.Y. etal. HFE gene knockout produces mouse model of hereditary hemochromatosis. Proc. Natl. Acad. Sci. USA95, 2492–2497 (1998).
7.Ludwiczek, S., Theurl, I., Bahram, S., Schümann, K. & Weiss, G. Regulatory networks for the control of body iron homeostasis and their dysregulation in HFE mediated hemochromatosis. J.Cell. Physiol.204, 489–499 (2005).
8.Tolosano, E. etal. Haptoglobin modifies the hemochromatosis phenotype in mice. Blood105, 3353–3355 (2005).
9.Delaby, C. etal. Renal handling of iron in mouse models of iron overload: recent concept. Am. J.Hematol.86, E42 (2011).
10.Gutiérrez, L., Vujic Spasic, M., Muckenthaler, M.U. & Lázaro, F.J. Quantitative magnetic analysis reveals ferritin-like iron as the most predominant iron-containing species in the murine Hfe-haemochromatosis. Biochim. Biophys. Acta1822, 1147–1153 (2012).
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