Iron metabolism in the pathogenesis of iron-induced kidney injury

Nature Reviews Nephrology

Volumn 9, Issue 7, 2013, Pages 385-398

  Martines, A M F ^a   Masereeuw, R ^b   Tjalsma, H ^a   Hoenderop, J G ^b   Wetzels, J F M ^b   Swinkels, D W ^a  

^a Laboratory of Genetic Endocrine and Metabolic Diseases   (Netherlands)

^b RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

CUBILIN; DEFEROXAMINE; EDETIC ACID; FERRITIN; FERROPORTIN; HAPTOGLOBIN; HEME OXYGENASE 1; HEMOGLOBIN; HEMOPEXIN; HEPCIDIN; HEPHAESTIN; IRON; IRON CHELATING AGENT; LACTOFERRIN; MEGALIN; MYOGLOBIN; NEUTROPHIL GELATINASE ASSOCIATED LIPOCALIN; TRANSFERRIN; TRANSFERRIN RECEPTOR;

GLOMERULOPATHY; GLOMERULUS FILTRATION; HEMOLYSIS; HUMAN; IRON ABSORPTION; IRON INDUCED KIDNEY INJURY; IRON METABOLISM; IRON OVERLOAD; IRON TRANSPORT; KIDNEY INJURY; NONHUMAN; OXIDATIVE STRESS; PATHOGENESIS; PRIORITY JOURNAL; REPERFUSION INJURY; REVIEW; RHABDOMYOLYSIS;

ACUTE KIDNEY INJURY; HUMANS; IRON; IRON OVERLOAD; KIDNEY; RENAL INSUFFICIENCY, CHRONIC;

EID: 84879794014     PISSN: 17595061     EISSN: 1759507X     Source Type: Journal    
DOI: 10.1038/nrneph.2013.98     Document Type: Review

References (129)

1. Al-Ismaili, Z., Piccioni, M. & Zappitelli, M. Rhabdomyolysis: pathogenesis of renal injury and management. Pediatr. Nephrol. 26, 1781-1788 (2011).
2. Hentze, M. W., Muckenthaler, M. U., Galy, B. & Camaschella, C. Two to tango: regulation of mammalian iron metabolism. Cell 142, 24-38 (2010).
3. Shah, S. V., Baliga, R., Rajapurkar, M. & Fonseca, V. A. Oxidants in chronic kidney disease. J. Am. Soc. Nephrol. 18, 16-28 (2007). (Pubitemid 46053418)
4. Kell, D. B. Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases. BMC Med. Genomics 2, 2 (2009).
5. Kroot, J. J. C., Tjalsma, H., Fleming, R. E. & Swinkels, D. W. Hepcidin in human iron disorders: diagnostic implications. Clin. Chem. 57, 1650-1669 (2011).
6. Veuthey, T., D'Anna, M. C. & Roque, M. E. Role of the kidney in iron homeostasis: renal expression of prohepcidin, ferroportin, and DMT1 in anemic mice. Am. J. Physiol. Renal Physiol. 295, F1213-F1221 (2008).
7. Haase, M., Mertens, P. R. & Haase-Fielitz, A. Renal stress in vivo in real-time-visualised by the NGAL reporter mouse. Nephrol. Dial. Transplant. 26, 2109-2111 (2011).
8. Haase-Fielitz, A. et al. Urine hepcidin has additive value in ruling out cardiopulmonary bypass-associated acute kidney injury: an observational cohort study. Crit. Care 15, R186 (2011).
9. Ho, J. et al. mass spectrometry-based proteomic analysis of urine in acute kidney injury following cardiopulmonary bypass: a nested case-control study. Am. J. Kidney Dis. 53, 584-595 (2009).
10. Ho, J. et al. Urinary hepcidin-25 and risk of acute kidney injury following cardiopulmonary bypass. Clin. J. Am. Nephrol. 6, 2340-2346 (2011).
11. Smith, C. P. & Thévenod, F. Iron transport and the kidney. Biochim. Biophys. Acta 1790, 724-730 (2009).
12. Brittenham, G. M. Iron-chelating therapy for transfusional iron overload. N. Engl. J. Med. 364, 146-156 (2011).
13. Swinkels, D. W., Janssen, M. C. H., Bergmans, J. & Marx, J. J. M. Hereditary hemochromatosis: genetic complexity and new diagnostic approaches. Clin. Chem. 52, 950-968 (2006). (Pubitemid 43794403)
14. Alfrey, A. C. & Hammond, W. S. Renal iron handling in the nephrotic syndrome. Kidney Int. 37, 1409-1413 (1990). (Pubitemid 20198021)
15. Paller, M. S. & Hedlund, B. O. Role of iron in postischemic renal injury in the rat. Kidney Int. 34, 474-480 (1988).
16. Moreno, J. A. et al. Haematuria: the forgotten CKD factor? Nephrol. Dial. Transplant. 27, 28-34 (2012).
17. Moreno, J. A. et al. AkI associated with macroscopic glomerular hematuria: clinical and pathophysiologic consequences. Clin. J. Am. Soc. Nephrol. 7, 175-184 (2012).
18. Garrick, M. D. & Garrick, L. M. Cellular iron transport. Biochim. Biophys. Acta 1790, 309-325 (2009).
19. Mori, K. et al. Endocytic delivery of lipocalin-siderophore-iron complex rescues the kidney from ischemia-reperfusion injury. J. Clin. Invest. 115, 610-621 (2005). (Pubitemid 40322235)
20. Paragas, N. et al. NGAL-siderocalin in kidney disease. Biochim. Biophys. Acta 1823, 1451-1458 (2012).
21. Chakraborty, S., Kaur, S., Guha, S. & Batra, S. K. The multifaceted roles of neutrophil gelatinase associated lipocalin (NGAL) in inflammation and cancer. Biochim. Biophys. Acta 1826, 129-169 (2012).
22. Pawar, R. D. et al. Neutrophil gelatinase-associated lipocalin is instrumental in the pathogenesis of antibody-mediated nephritis in mice. Arthritis Rheum. 64, 1620-1631 (2012).
23. Barasch, J. & Qiu, A. Mutant NGAL proteins and uses thereof. International patent application WO/2011/149962 (2011).
24. Rajapurkar, M. M., Hegde, U., Bhattacharya, A., Alam, M. G. & Shah, S. V. Effect of deferiprone, an oral iron chelator, in diabetic and non-diabetic glomerular disease. Toxicol. Mech. Methods 23, 5-10 (2013).
25. Goraya, N., Simoni, J., Jo, C. & Wesson, D. E. Dietary acid reduction with fruits and vegetables or bicarbonate attenuates kidney injury in patients with a moderately reduced glomerular filtration rate due to hypertensive nephropathy. Kidney Int. 81, 86-93 (2012).
26. Zhang, D., Meyron-Holtz, E. & Rouault, T. A. Renal iron metabolism: transferrin iron delivery and the role of iron regulatory proteins. J. Am. Soc. Nephrol. 18, 401-406 (2007). (Pubitemid 46193305)
27. García-Montoya, I. A., Cendón, T. S., Arévalo- Gallegos, S. & Rascón-Cruz, Q. Lactoferrin a multiple bioactive protein: an overview. Biochim. Biophys. Acta 1820, 226-236 (2012).
28. Adlerova, L., Bartoskova, A. & Faldyna, M. Lactoferrin: a review. Vet. Med. (Praha). 53, 457-468 (2008).
29. Åbrink, M., Larsson, E., Gobl, A. & Hellman, L. Expression of lactoferrin in the kidney: Implications for innate immunity and iron metabolism. Kidney Int. 57, 2004-2010 (2000). (Pubitemid 30252292)
30. Norden, A. G. W. et al. Glomerular protein sieving and implications for renal failure in Fanconi syndrome. Kidney Int. 60, 1885-1892 (2001). (Pubitemid 32999994)
31. Itzhaki, R. F. & Belcher, E. H. Studies on plasma iron in the rat. II. Plasma iron concentration and plasma iron-binding capacity. Arch. Biochem. Biophys. 92, 74-80 (1961).
32. Tanner, G. A. Glomerular sieving coefficient of serum albumin in the rat: a two-photon microscopy study. Am. J. Physiol. Renal Physiol. 296, F1258-F1265 (2009).
33. Cohen, L. A. et al. Serum ferritin is derived primarily from macrophages through a nonclassical secretory pathway. Blood 116, 1574-1584 (2010).
34. Marzolo, M. P. & Farfán, P. New insights into the roles of megalin/LRP2 and the regulation of its functional expression. Biol. Res. 44, 89-105 (2011).
35. Le Blanc, S., Garrick, M. D. & Arredondo, M. Heme carrier protein 1 transports heme and is involved in heme-Fe metabolism. Am. J. Physiol Cell Physiol. 302, C1780-C1785 (2012).
36. Nath, K. A. Heme oxygenase-1: a provenance for cytoprotective pathways in the kidney and other tissues. Kidney Int. 70, 432-443 (2006). (Pubitemid 44141569)
37. Zarjou, A. et al. proximal tubule H-ferritin mediates renal iron trafficking and confers protection in acute kidney injury. J. Am. Soc. Nephrol. 23, 96A (2012).
38. Langelueddecke, C. et al. Lipocalin-2 (24p3/neutrophil gelatinase-associated lipocalin (NGAL)) receptor is expressed in distal nephron and mediates protein endocytosis. J. Biol. Chem. 287, 159-169 (2012).
39. Khan, A. A. & Quigley, J. G. Control of intracellular heme levels: heme transporters and heme oxygenases. Biochim. Biophys. Acta 1813, 668-682 (2011).
40. Cheng, X., Shen, D., Samie, M. & Xu, H. Mucolipins: intracellular TRPML1-3 channels. FEBS Lett. 584, 2013-2021 (2010).
41. Jenkitkasemwong, S., Wang, C. Y., Mackenzie, B. & Knutson, M. D. Physiologic implications of metal-ion transport by ZIP14 and ZIP8. Biometals 25, 643-655 (2012).
42. Yanatori, I. et al. Heme and non-heme iron transporters in non-polarized and polarized cells. BMC Cell Biol. 11, 39 (2010).
43. Vesey, D. A. Transport pathways for cadmium in the intestine and kidney proximal tubule: focus on the interaction with essential metals. Toxicol. Lett. 198, 13-19 (2010).
44. Wolff, N. A. et al. Ferroportin 1 is expressed basolaterally in rat kidney proximal tubule cells and iron excess increases its membrane trafficking. J. Cell. Mol. Med. 15, 209-219 (2011).
45. Yang, Z. et al. Kinetics and specificity of feline leukemia virus subgroup C receptor (FLVCR) export function and its dependence on hemopexin. J. Biol. Chem. 285, 28874-28882 (2010).
46. Camborieux, L., Julia, V., Pipy, B. & Swerts, J. P. Respective roles of inflammation and axonal breakdown in the regulation of peripheral nerve hemopexin: an analysis in rats and in C57BL/Wlds mice. J. Neuroimmunol. 107, 29-41 (2000). (Pubitemid 30243128)
47. Tolosano, E., Fagoonee, S., Morello, N., Vinchi, F. & Fiorito, V. Heme scavenging and the other facets of hemopexin. Antioxid. Redox Signal. 12, 305-320 (2010).
48. Moestrup, S. K., Gliemann, J. & Pallesen, G. Distribution of the 2-macroglobulin receptor/low density lipoprotein receptor-related protein in human tissues. Cell Tissue Res. 269, 375-382 (1992).
49. Zager, R. A., Vijayan, A. & Johnson, A. C. M. Proximal tubule haptoglobin gene activation is an integral component of the acute kidney injury "stress response". Am. J. Physiol. Renal Physiol. 303, F139-F148 (2012).
50. Van Gorp, H., Delputte, P. L. & Nauwynck, H. J. Scavenger receptor CD163, a Jack-of-all-trades and potential target for cell-directed therapy. Mol. Immunol. 47, 1650-1660 (2010).
51. Sponsel, H. T. et al. Effect of iron on renal tubular epithelial cells. Kidney Int. 50, 436-444 (1996). (Pubitemid 26274370)
52. Sheerin, N. S., Sacks, S. H. & Fogazzi, G. B. In vitro erythrophagocytosis by renal tubular cells and tubular toxicity by haemoglobin and iron. Nephrol. Dial. Transplant. 14, 1391-1397 (1999). (Pubitemid 29241728)
53. Shvartsman, M. & Cabantchik, Z. I. Intracellular iron trafficking: role of cytosolic ligands. Biometals 25, 711-723 (2012).
54. Philpott, C. C. Coming into view: eukaryotic iron chaperones and intracellular iron delivery. J. Biol. Chem. 287, 13518-13523 (2012).
55. Johnson, A. C. M., Becker, K. & Zager, R. A. Parenteral iron formulations differentially affect MCP-1, HO-1, and NGAL gene expression and renal responses to injury. Am. J. Physiol. Renal Physiol 299, F426-F435 (2010).
56. 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). (Pubitemid 40934644)
57. Liu, Q. S., Nilsen-Hamilton, M. & Xiong, S. D. Synergistic regulation of the acute phase protein SIP24/24p3 by glucocorticoid and pro-inflammatory cytokines. Acta Physiologica Sinica 55, 525-529 (2003). (Pubitemid 37370013)
58. Roudkenar, M. H. et al. Oxidative stress induced lipocalin 2 gene expression: addressing its expression under the harmful conditions. J. Radiat. Res. 48, 39-44 (2007). (Pubitemid 46219475)
59. Roudkenar, M. H. et al. Upregulation of neutrophil gelatinase-associated lipocalin, NGAL/Lcn2, in thalassemia patients. Arch. Med. Res. 39, 402-407 (2008).
60. Zager, R. A. & Burkhart, K. Myoglobin toxicity in proximal human kidney cells: roles of Fe, Ca2+, H2O2, and terminal mitochondrial electron transport. Kidney Int. 51, 728-738 (1997). (Pubitemid 27157957)
61. Paller, M. S. & Hedlund, B. E. Extracellular iron chelators protect kidney cells from hypoxia/reoxygenation. Free Radic. Biol. Med. 17, 597-603 (1994). (Pubitemid 24367942)
62. Kovtunovych, G., Eckhaus, M. A., Ghosh, M. C., Ollivierre-Wilson, H. & Rouault, T. A. Dysfunction of the heme recycling system in heme oxygenase 1-deficient mice: effects on macrophage viability and tissue iron distribution. Blood 116, 6054-6062 (2010).
63. 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. Iranian Med. 15, 91-94 (2012).
64. Sears, D. A., Anderson, P. R., Foy, A. L., Williams, H. L. & Crosby, W. H. Urinary iron excretion and renal metabolism of hemoglobin in hemolytic diseases. Blood 28, 708-725 (1966).
65. Schein, A., Enriquez, C., Coates, T. D. & Wood, J. C. Magnetic resonance detection of kidney iron deposition in sickle cell disease: a marker of chronic hemolysis. J. Magn. Reson. Imaging 28, 698-704 (2008).
66. Ballarín, J. et al. Acute renal failure associated to paroxysmal nocturnal haemoglobinuria leads to intratubular haemosiderin accumulation and CD163 expression. Nephrol. Dial. Transplant. 26, 3408-3411 (2011).
67. Fervenza, F. C. et al. Induction of heme oxygenase-1 and ferritin in the kidney in warm antibody hemolytic anemia. Am. J. Kidney Dis. 52, 972-977 (2008).
68. Rakow-Penner, R., Glader, B., Yu, H. & Vasanawala, S. Adrenal and renal corticomedullary junction iron deposition in red cell aplasia. Pediatr. Radiol. 40, 1955-1957 (2010).
69. Rous, P. Urinary siderosis: hemosiderin granules in the urine as an aid in the diagnosis of pernicious anemia, hemochromatosis, and other diseases causing siderosis of the kidney. J. Exp. Med. 28, 645-658 (1918).
70. Wang, H. et al. Iron deposition in renal biopsy specimens from patients with kidney diseases. Am. J. Kidney Dis. 38, 1038-1044 (2001). (Pubitemid 33022181)
71. Ueda, N., Baliga, R. & Shah, S. V. Role of 'catalytic' iron in an animal model of minimal change nephrotic syndrome. Kidney Int. 49, 370-373 (1996). (Pubitemid 26050318)
72. Zager, R. A., Foerder, C. & Bredl, C. The influence of mannitol on myoglobinuric acute renal failure: functional, biochemical, and morphological assessments. J. Am. Soc. Nephrol. 2, 848-855 (1991).
73. Delaby, C. et al. Renal handling of iron in mouse models of iron overload: recent concept. Am. J. Hematol. 86, E42 (2011).
74. Baliga, R., Zhang, Z., Baliga, M. & Shah, S. V. Evidence for cytochrome P-450 as a source of catalytic iron in myoglobinuric acute renal failure. Kidney Int. 49, 362-369 (1996). (Pubitemid 26051824)
75. 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. Acta 1822, 1147-1153 (2012).
76. Harris, D. C. H. & Tay, Y. C. Mitochondrial function in rat renal cortex in response to proteinuria and iron. Clin. Exp. Pharmacol. Physiol. 24, 916-922 (1997). (Pubitemid 27494299)
77. Harris, D. C. H., Tay, C. & Nankivell, B. J. Lysosomal iron accumulation and tubular damage in rat puromycin nephrosis and ageing. Clin. Exp. Pharmacol. Physiol. 21, 73-81 (1994). (Pubitemid 24141717)
78. Nankivell, B. J. & Harris, D. C. H. Iron depletion in the remnant kidney. Nephron 70, 340-347 (1995).
79. Nankivell, B. J., Chen, J., Boadle, R. A. & Harris, D. C. H. The role of tubular iron accumulation in the remnant kidney. J. Am. Soc. Nephrol. 4, 1598-1607 (1993). (Pubitemid 24977035)
80. Viau, A. et al. Lipocalin 2 is essential for chronic kidney disease progression in mice and humans. J. Clin. Invest. 120, 4065-4076 (2010).
81. Remuzzi, A., Puntorieri, S., Brugnetti, B., Bertani, T. & Remuzzi, G. Renoprotective effect of low iron diet and its consequence on glomerular hemodynamics. Kidney Int. 39, 647-652 (1991).
82. De Vries, B. et al. Reduction of circulating redox-active iron by apotransferrin protects against renal ischemia-reperfusion injury. Transplantation 77, 669-675 (2004). (Pubitemid 38366970)
83. Mishra, J. et al. Amelioration of ischemic acute renal injury by neutrophil gelatinase-associated lipocalin. J. Am. Soc. Nephrol. 15, 3073-3082 (2004). (Pubitemid 39578839)
84. Michelakakis, H. et al. Iron overload and urinary lysosomal enzyme levels in ?-thalassaemia major. Eur. J. Pediatr. 156, 602-604 (1997). (Pubitemid 27351845)
85. Lin, J. L., Lin-Tan, D. T., Hsu, K. H. & Yu, C. C. Environmental lead exposure and progression of chronic renal diseases in patients without diabetes. N. Engl. J. Med. 348, 277-286 (2003).
86. Aldudak, B. et al. Renal function in pediatric patients with thalassemia major. Pediatr. Nephrol. 15, 109-112 (2000).
87. Koliakos, G. et al. Urine biochemical markers of early renal dysfunction are associated with iron overload in ?-thalassaemia. Clin. Lab. Haematol. 25, 105-109 (2003). (Pubitemid 36458159)
88. Nath, K. A. et al. Heme protein-induced chronic renal inflammation: suppressive effect of induced heme oxygenase-11. Kidney Int. 59, 106-117 (2001). (Pubitemid 32055219)
89. Boutaud, O. & Roberts II, L. J. Mechanism-based therapeutic approaches to rhabdomyolysis-induced renal failure. Free Radic. Biol. Med. 51, 1062-1067 (2011).
90. Hsiao, P. J., Wang, S. C., Wen, M. C., Diang, L. K. & Lin, S. H. Fanconi syndrome and CKD in a patient with paroxysmal nocturnal hemoglobinuria and hemosiderosis. Am. J. Kidney Dis. 55, e1-e5 (2010).
91. Leonardi, P. & Ruol, A. Renal hemosiderosis in the hemolytic anemias: diagnosis by means of needle biopsy. Blood 16, 1029-1038 (1960).
92. Zager, R. A. Rhabdomyolysis and myohemoglobinuric acute renal failure. Kidney Int. 49, 314-326 (1996). (Pubitemid 26051819)
93. Zager, R. A., Johnson, A. C. M. & Becker, K. Renal cortical hemopexin accumulation in response to acute kidney injury. Am. J. Physiol. Renal Physiol. 303, F1460-F1472 (2012).
94. Tolosano, E. et al. Haptoglobin modifies the hemochromatosis phenotype in mice. Blood 105, 3353-3355 (2005).
95. Zhou, X. Y. et al. HFE gene knockout produces mouse model of hereditary hemochromatosis. Proc. Natl Acad. Sci. USA 95, 2492-2497 (1998). (Pubitemid 28145969)
96. Muncie, J. & Campbell, J. S. Alpha and beta thalassemia. Am. Fam. Physician 80, 339-344 (2009).
97. Amer, J., Goldfarb, A. & Fibach, E. Flow cytometric analysis of the oxidative status of normal and thalassemic red blood cells. Cytometry A 60, 73-80 (2004). (Pubitemid 38859203)
98. Chiou, S. S. et al. Lipid peroxidation and antioxidative status in thalassemia major patients with or without hepatitis C virus infection. Clin. Chem. Lab. Med. 44, 1226-1233 (2006).
99. Livrea, M. A. et al. Oxidative stress and antioxidant status in thalassemia major: iron overload and depletion of lipid-soluble antioxidants. Blood 88, 3608-3614 (1996). (Pubitemid 26365599)
100. Walter, P. B. et al. Oxidative stress and inflammation in iron-overloaded patients with ?-thalassaemia or sickle cell disease. Br. J. Haematol. 135, 254-263 (2006). (Pubitemid 44401624)
101. Mackinnon, B. et al. Urinary transferrin, high molecular weight proteinuria and the progression of renal disease. Clin. Nephrol. 59, 252-258 (2003).
102. Brown, E. A., Sampson, B., Muller, B. R. & Curtis, J. R. Urinary iron loss in the nephrotic syndrome-an unusual cause of iron deficiency with a note on urinary copper losses. Postgrad. Med. J. 60, 125-128 (1984). (Pubitemid 14182883)
103. Howard, R. L., Buddington, B. & Alfrey, A. C. Urinary albumin, transferrin and iron excretion in diabetic patients. Kidney Int. 40, 923-926 (1991).
104. Prinsen, B. H. C. M. et al. Transferrin synthesis is increased in nephrotic patients insufficiently to replace urinary losses. J. Am. Soc. Nephrol. 12, 1017-1025 (2001). (Pubitemid 32378343)
105. Ellis, D. Anemia in the course of the nephrotic syndrome secondary to transferrin depletion. J. Pediatr. 90, 953-955 (1977).
106. Naito, Y. et al. Effect of iron restriction on renal damage and mineralocorticoid receptor signaling in a rat model of chronic kidney disease. J. Hypertens. 30, 2192-2201 (2012).
107. Mahmoodi, B. K. et al. Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without hypertension: a meta-analysis. Lancet 380, 1649-1661 (2012).
108. Gutierrez, E. et al. Oxidative stress, macrophage infiltration and CD163 expression are determinants of long-term renal outcome in macrohematuria-induced acute kidney injury of IgA nephropathy. Nephron Clin. Pract. 121, C42-C53 (2012).
109. Eller, K., Banas, M. C., Kirsch, A. H. & Rosenkranz, A. R. Lipocalin-2 is an endogenous inhibitor of inflammation in murine nephrotoxic serum nephritis. J. Am. Soc. Nephrol. 23, 563A (2012).
110. Lipton, P. Ischemic cell death in brain neurons. Physiol. Rev. 79, 1431-1568 (1999). (Pubitemid 29473320)
111. Sola, A., Ventayol, A. & Hotter, G. Lcn-2 over-expressing bone marrow-derived macrophages promote renal regeneration. J. Am. Soc. Nephrol. 23, 106A (2012).
112. Jung, M. et al. Infusion of IL-10-expressing cells protects against renal ischemia through induction of lipocalin-2. Kidney Int. 81, 969-982 (2012).
113. Kozyraki, R. et al. Megalin-dependent cubilin-mediated endocytosis is a major pathway for the apical uptake of transferrin in polarized epithelia. Proc. Natl Acad. Sci. USA 98, 12491-12496 (2001). (Pubitemid 33019973)
114. Peters, H. P. E. et al. Tubular reabsorption and local production of urine hepcidin-25. BMC Nephrology 14, 70 (2013).
115. Ludwiczek, S. et al. Ca2+ channel blockers reverse iron overload by a new mechanism via divalent metal transporter-1. Nat. Med. 13, 448-454 (2007). (Pubitemid 46562464)
116. Liu, C. B., Wu, B., Xiao, M. & Wang, L. Q. Effects of nifedipine on iron deposits and nutritional metabolism in chronic iron-overloaded rats. Chinese J. Pharmacol. Toxicol. 25, 77-82 (2011).
117. Huang, X. P., Thiessen, J. J., Spino, M. & Templeton, D. M. Transport of iron chelators and chelates across MDCK cell monolayers: Implications for iron excretion during chelation therapy. Int. J. Hematol. 91, 401-412 (2010).
118. Abbas, M. et al. Evaluation of urinary excretion and renal clearance of deferiprone, creatinine, iron and zinc in human. Asian J. Chem. 6, 4583-4592 (2009).
119. Baum, M. Renal Fanconi syndrome secondary to deferasirox: where there is smoke there is fire. J. Pediatr. Hematol. Oncol. 32, 525-526 (2010).
120. Suzuki, Y. A. & Lönnerdal, B. Baculovirus expression of mouse lactoferrin receptor and tissue distribution in the mouse. Biometals 17, 301-309 (2004). (Pubitemid 38987154)
121. Zhao, R., Diop-Bove, N., Visentin, M. & Goldman, I. D. Mechanisms of membrane transport of folates into cells and across epithelia. Annu. Rev. Nutr. 31, 177-201 (2011).
122. Shepard, M., Dhulipala, P., Kabaria, S., Abraham, N. G. & Lianos, E. A. Heme oxygenase-1 localization in the rat nephron. Nephron 92, 660-664 (2002).
123. Branten, A. J. W., Swinkels, D. W., Klasen, I. S. & Wetzels, J. F. M. Serum ferritin levels are increased in patients with glomerular diseases and proteinuria. Nephrol. Dial. Transplant. 19, 2754-2760 (2004). (Pubitemid 39480969)
124. Paragas, N. et al. The Ngal reporter mouse detects the response of the kidney to injury in real time. Nat. Med. 17, 216-223 (2011).
125. Haase, V. H. Hemoglobin in the kidney: breaking with traditional dogma. J. Am. Soc. Nephrol. 19, 1440-1441 (2008).
126. Rodríguez-Capote, K. et al. Utility of urine myoglobin for the prediction of acute renal failure in patients with suspected rhabdomyolysis: a systematic review. Clin. Chem. 55, 2190-2197 (2009).
127. Kulaksiz, H. et al. The iron-regulatory peptide hormone hepcidin: expression and cellular localization in the mammalian kidney. J. Endocrinol. 184, 361-370 (2005). (Pubitemid 40340171)
128. Kapojos, J. J. et al. Production of hemopexin by TNF-stimulated human mesangial cells. Kidney Int. 63, 1681-1686 (2003). (Pubitemid 36513313)
129. Baliga, R., Ueda, N. & Shah, S. V. Increase in bleomycin-detectable iron in ischaemia/reperfusion injury to rat kidneys. Biochem. J. 291, 901-905 (1993). (Pubitemid 23148470)