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  • Review Article
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Deferasirox nephrotoxicity—the knowns and unknowns

Nature Reviews Nephrology volume 10, pages 574–586 (2014)Cite this article

Subjects

Key Points

  • Deferasirox is an oral iron chelator with nephrotoxic potential that could result in decreased glomerular filtration requiring dialysis and in proximal tubular dysfunction

  • Although deferasirox nephrotoxicity has been reported to promote tubular cell injury, the molecular and cellular mechanisms are poorly understood

  • Postmarketing monitoring of potential long-term effects of chronic deferasirox treatment on kidney function is required

  • Careful selection and monitoring of patients treated with deferasirox might decrease the risks of serious renal adverse effects

Abstract

In 2005, the oral iron chelator deferasirox was approved by the FDA for clinical use as a first-line therapy for blood-transfusion-related iron overload. Nephrotoxicity is the most serious and frequent adverse effect of deferasirox treatment. This nephrotoxicity can present as an acute or chronic decrease in glomerular filtration rate (GFR). Features of proximal tubular dysfunction might also be present. In clinical trials and observational studies, GFR is decreased in 30–100% of patients treated with deferasirox, depending on dose, method of assessment and population studied. Nephrotoxicity is usually nonprogressive and/or reversible and rapid iron depletion is one of several risk factors. Scarce data are available on the molecular mechanisms of nephrotoxicity and the reasons for the specific proximal tubular sensitivity to the drug. Although deferasirox promotes apoptosis of cultured proximal tubular cells, the trigger has not been well characterized. Observational studies are required to track current trends in deferasirox prescription, assess the epidemiology of deferasirox nephrotoxicity in routine clinical practice, explore the effect on outcomes of various monitoring and dose-adjustment protocols and elucidate the long-term consequences of the different features of nephrotoxicity. Deferasirox nephrotoxicity can be more common in the elderly; thus, specific efforts should be dedicated to investigate the effect of deferasirox use in this group of patients.

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Figure 1: Deferasirox structure.
Figure 2: Incidence of increased sCr levels in patients treated with deferasirox.
Figure 3: Distribution of deferasirox nephrotoxicity as assessed by sCr levels.
Figure 4: Molecular mechanisms of deferasirox toxicity.

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References

  1. Nick, H. et al. ICL670A: preclinical profile. Adv. Exp. Med. Biol. 509, 185–203 (2002).

    Article  CAS  PubMed  Google Scholar 

  2. Taher, A. et al. Efficacy and safety of deferasirox, an oral iron chelator, in heavily iron-overloaded patients with β-thalassaemia: the ESCALATOR study. Eur. J. Haematol. 82, 458–465 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Kwiatkowski, J. L. Real-world use of iron chelators. Hematology Am. Soc. Hematol. Educ. Program 2011, 451–458 (2011).

    Article  PubMed  Google Scholar 

  4. Food and Drug Administration. Drug Approval Package [online], (2006).

  5. The European Medicines Agency. EPAR summary for the public [online], (2013).

  6. Riva, A. Deferasirox's toxicity. Lancet 382, 127–128 (2013).

    Article  PubMed  Google Scholar 

  7. The European Medicines Agency. EMEA/COMP/50/02 Rev. 2 [online], (2007).

  8. The European Medicines Agency. EPAR Product Information [online], (2014).

  9. Vichinsky, E. et al. A randomised comparison of deferasirox versus deferoxamine for the treatment of transfusional iron overload in sickle cell disease. Br. J. Haematol. 136, 501–508 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Food and Drug Administration. Prescribing information [online], (2013).

  11. Greenberg, P. L. et al. Prospective assessment of effects on iron-overload parameters of deferasirox therapy in patients with myelodysplastic syndromes. Leuk. Res. 34, 1560–1565 (2010).

    Article  CAS  PubMed  Google Scholar 

  12. Porter, J. et al. Relative response of patients with myelodysplastic syndromes and other transfusion-dependent anaemias to deferasirox (ICL670): a 1-yr prospective study. Eur. J. Haematol. 80, 168–176 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Chirnomas, D. et al. Deferasirox pharmacokinetics in patients with adequate versus inadequate response. Blood 114, 4009–4013 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Taher, A. et al. Efficacy and safety of deferasirox doses of >30 mg/kg per d in patients with transfusion-dependent anaemia and iron overload. Br. J. Haematol. 147, 752–759 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Meerpohl, J. J. et al. Deferasirox for managing iron overload in people with thalassaemia. Cochrane Database of Systematic Reviews, Issue 2. Art. No.: CD007476. http://dx.doi.org/10.1002/14651858.CD007476.pub2.

  16. Food and Drug Administration. Important drug warning [online], (2010).

  17. Kontoghiorghes, G. J. Turning a blind eye to deferasirox's toxicity? Lancet 381, 1183–1184 (2013).

    Article  CAS  PubMed  Google Scholar 

  18. Anapol Schwartz, LLC. FDA reports [online], (2012).

  19. eHealthMe. Review: could Exjade cause blood creatinine increased? [online], (2014).

  20. Food and Drug Administration. New molecular entity (NME) — early safety findings [online], (2007).

  21. Hirschberg, R., Bennett, W., Scheinman, J., Coppo, R. & Ponticelli, C. Acute kidney injury due to deferoxamine in a renal transplant patient. Nephrol. Dial. Transplant. 23, 2704–2705 (2008).

    Article  PubMed  Google Scholar 

  22. Cappellini, M. D. et al. A phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with β-thalassemia. Blood 107, 3455–3462 (2006).

    Article  CAS  PubMed  Google Scholar 

  23. Piga, A. et al. Randomized phase II trial of deferasirox (Exjade, ICL670), a once-daily, orally-administered iron chelator, in comparison to deferoxamine in thalassemia patients with transfusional iron overload. Haematologica 91, 873–880 (2006).

    CAS  PubMed  Google Scholar 

  24. Galanello, R. et al. Phase II clinical evaluation of deferasirox, a once-daily oral chelating agent, in pediatric patients with β-thalassemia major. Haematologica 91, 1343–1351 (2006).

    CAS  PubMed  Google Scholar 

  25. Shemesh, O., Golbetz, H., Kriss, J. P. & Myers, B. D. Limitations of creatinine as a filtration marker in glomerulopathic patients. Kidney Int. 28, 830–838 (1985).

    Article  CAS  PubMed  Google Scholar 

  26. Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO clinical practice guideline for acute kidney jnjury. Kidney Int. Suppl. 2, 1–138 (2012).

  27. Rafat, C., Fakhouri, F., Ribeil, J. A., Delarue, R. & Le Quintrec, M. Fanconi syndrome due to deferasirox. Am. J. Kidney Dis. 54, 931–934 (2009).

    Article  CAS  PubMed  Google Scholar 

  28. Yew, C. T. et al. Acute interstitial nephritis secondary to deferasirox causing acute renal injury needing short-term dialysis. Nephrology (Carlton) 15, 377 (2010).

    Article  Google Scholar 

  29. Brosnahan, G., Gokden, N. & Swaminathan, S. Acute interstitial nephritis due to deferasirox: a case report. Nephrol. Dial. Transplant. 23, 3356–3358 (2008).

    Article  PubMed  Google Scholar 

  30. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int. Suppl. 3, 1–150 (2013).

  31. Milat, F. et al. A case of hypophosphatemic osteomalacia secondary to deferasirox therapy. J. Bone Miner. Res. 27, 219–222 (2012).

    Article  PubMed  Google Scholar 

  32. Papadopoulos, N., Vasiliki, A., Aloizos, G., Tapinis, P. & Kikilas, A. Hyperchloremic metabolic acidosis due to deferasirox in a patient with beta thalassemia major. Ann. Pharmacother. 44, 219–221 (2010).

    Article  PubMed  Google Scholar 

  33. Baum, M. Renal Fanconi syndrome secondary to deferasirox: where there is smoke there is fire. J. Pediatr. Hematol. Oncol. 32, 525–526 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  34. Grangé, S., Bertrand, D. M., Guerrot, D., Eas, F. & Godin, M. Acute renal failure and Fanconi syndrome due to deferasirox. Nephrol. Dial. Transplant. 25, 2376–2378 (2010).

    Article  CAS  PubMed  Google Scholar 

  35. Even-Or, E., Becker-Cohen, R. & Miskin, H. Deferasirox treatment may be associated with reversible renal Fanconi syndrome. Am. J. Hematol. 85, 132–134 (2010).

    PubMed  Google Scholar 

  36. Rheault, M. N., Bechtel, H., Neglia, J. P. & Kashtan, C. E. Reversible Fanconi syndrome in a pediatric patient on deferasirox. Pediatr. Blood Cancer 56, 674–676 (2011).

    Article  PubMed  Google Scholar 

  37. Chueh, H. W. et al. Iron chelation treatment with deferasirox prior to high-dose chemotherapy and autologous stem cell transplantation may reduce the risk of hepatic veno-occlusive disease in children with high-risk solid tumors. Pediatr. Blood Cancer 58, 441–447 (2012).

    Article  PubMed  Google Scholar 

  38. Dubourg, L. et al. Deferasirox-induced renal impairment in children: an increasing concern for pediatricians. Pediatr. Nephrol. 27, 2115–2122 (2012).

    Article  PubMed  Google Scholar 

  39. Wei, H. Y., Yang, C. P., Cheng, C. H. & Lo, F. S. Fanconi syndrome in a patient with β-thalassemia major after using deferasirox for 27 months. Transfusion 51, 949–954 (2011).

    Article  PubMed  Google Scholar 

  40. Yacobovich, J. et al. Acquired proximal renal tubular dysfunction in β-thalassemia patients treated with deferasirox. J. Pediatr. Hematol. Oncol. 32, 564–567 (2010).

    Article  CAS  PubMed  Google Scholar 

  41. Yusuf, B., McPhedran, P. & Brewster, U. C. Hypocalcemia in a dialysis patient treated with deferasirox for iron overload. Am. J. Kidney Dis. 52, 587–590 (2008).

    Article  PubMed  Google Scholar 

  42. European Medicines Agency. Scientific discussion [online], (2006).

  43. Vichinsky, E. et al. Efficacy and safety of deferasirox compared with deferoxamine in sickle cell disease: Two-year results including pharmacokinetics and concomitant hydroxyurea. Am. J. Hematol. 88, 1068–1073 (2013).

    Article  CAS  PubMed  Google Scholar 

  44. European Medicines Agency. Assessment report [online], (2013).

  45. Cancado, R. et al. Two-year analysis of efficacy and safety of deferasirox treatment for transfusional iron overload in sickle cell anemia patients. Acta Haematol. 128, 113–118 (2012).

    Article  CAS  PubMed  Google Scholar 

  46. Cappellini, M. D. et al. Iron chelation with deferasirox in adult and pediatric patients with thalassemia major: efficacy and safety during 5 years' follow-up. Blood 118, 884–893 (2011).

    Article  CAS  PubMed  Google Scholar 

  47. Gattermann, N. et al. Deferasirox in iron-overloaded patients with transfusion-dependent myelodysplastic syndromes: Results from the large 1-year EPIC study. Leuk. Res. 34, 1143–1150 (2010).

    Article  CAS  PubMed  Google Scholar 

  48. Kennedy, G. A. et al. A prospective phase II randomized study of deferasirox to prevent iatrogenic iron overload in patients undertaking induction/consolidation chemotherapy for acute myeloid leukaemia. Br. J. Haematol. 161, 794–801 (2013).

    Article  CAS  PubMed  Google Scholar 

  49. Lee, J. W. et al. Iron chelation therapy with deferasirox in patients with aplastic anemia: a subgroup analysis of 116 patients from the EPIC trial. Blood 116, 2448–2454 (2010).

    Article  CAS  PubMed  Google Scholar 

  50. List, A. F. et al. Deferasirox reduces serum ferritin and labile plasma iron in RBC transfusion-dependent patients with myelodysplastic syndrome. J. Clin. Oncol. 30, 2134–2139 (2012).

    Article  CAS  PubMed  Google Scholar 

  51. Metzgeroth, G. et al. Deferasirox in MDS patients with transfusion-caused iron overload—a phase-II study. Ann. Hematol. 88, 301–310 (2009).

    Article  CAS  PubMed  Google Scholar 

  52. Miyazawa, K. et al. A safety, pharmacokinetic and pharmacodynamic investigation of deferasirox (Exjade, ICL670) in patients with transfusion-dependent anemias and iron-overload: a phase I study in Japan. Int. J. Hematol. 88, 73–81 (2008).

    Article  CAS  PubMed  Google Scholar 

  53. Nolte, F. et al. Results from a 1-year, open-label, single arm, multi-center trial evaluating the efficacy and safety of oral deferasirox in patients diagnosed with low and int-1 risk myelodysplastic syndrome (MDS) and transfusion-dependent iron overload. Ann. Hematol. 92, 191–198 (2013).

    Article  CAS  PubMed  Google Scholar 

  54. Pennell, D. J. et al. Deferasirox for up to 3 years leads to continued improvement of myocardial T2* in patients with β-thalassemia major. Haematologica 97, 842–848 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Phatak, P. et al. A phase 1/2, dose-escalation trial of deferasirox for the treatment of iron overload in HFE-related hereditary hemochromatosis. Hepatology 52, 1671–1779 (2010).

    Article  CAS  PubMed  Google Scholar 

  56. Taher, A. T. et al. Deferasirox reduces iron overload significantly in nontransfusion-dependent thalassemia: 1-year results from a prospective, randomized, double-blind, placebo-controlled study. Blood 120, 970–977 (2012).

    Article  CAS  PubMed  Google Scholar 

  57. Vichinsky, E. et al. Long-term safety and efficacy of deferasirox (Exjade) for up to 5 years in transfusional iron-overloaded patients with sickle cell disease. Br. J. Haematol. 154, 387–397 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Voskaridou, E. et al. Deferasirox effectively decreases iron burden in patients with double heterozygous HbS/β-thalassemia. Ann. Hematol. 90, 11–15 (2011).

    Article  CAS  PubMed  Google Scholar 

  59. Wood, J. C. et al. The effect of deferasirox on cardiac iron in thalassemia major: impact of total body iron stores. Blood 116, 537–543 (2010).

    Article  CAS  PubMed  Google Scholar 

  60. Al-Khabori, M. et al. Side effects of deferasirox iron chelation in patients with beta thalassemia major or intermedia. Oman. Med. J. 28, 121–124 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Economou, M. et al. Renal dysfunction in patients with beta-thalassemia major receiving iron chelation therapy either with deferoxamine and deferiprone or with deferasirox. Acta Haematol. 123, 148–152 (2010).

    Article  CAS  PubMed  Google Scholar 

  62. Efthimia, V. et al. Nephrolithiasis in beta thalassemia major patients treated with deferasirox: an advent or an adverse event? A single Greek center experience. Ann. Hematol. 92, 263–265 (2013).

    Article  PubMed  Google Scholar 

  63. Tunç, B. et al. Deferasirox therapy in children with Fanconi aplastic anemia. J. Pediatr. Hematol. Oncol. 34, 247–251 (2012).

    Article  CAS  PubMed  Google Scholar 

  64. Unal, S., Hazirolan, T., Eldem, G. & Gumruk, F. The effects of deferasirox on renal, cardiac and hepatic iron load in patients with β-thalassemia major: preliminary results. Pediatr. Hematol. Oncol. 28, 217–221 (2011).

    Article  CAS  PubMed  Google Scholar 

  65. Cermak, J. et al. A comparative study of deferasirox and deferiprone in the treatment of iron overload in patients with myelodysplastic syndromes. Leuk. Res. 37, 1612–1615 (2013).

    Article  CAS  PubMed  Google Scholar 

  66. Ktena, Y. P., Athanasiadou, A., Lambrou, G., Adamaki, M. & Moschovi, M. Iron chelation with deferasirox for the treatment of secondary hemosiderosis in pediatric oncology patients: a single-center experience. J. Pediatr. Hematol. Oncol. 35, 447–450 (2013).

    Article  CAS  PubMed  Google Scholar 

  67. Karimi, M. et al. Iranian experience of deferasirox (Exjade®) in transfusion-dependent patients with iron overload: what is the most effective dose based on serum ferritin levels? Hematology 17, 367–371 (2012).

    Article  CAS  PubMed  Google Scholar 

  68. Aydinok, Y. et al. Observational study comparing long-term safety and efficacy of deferasirox with desferrioxamine therapy in chelation-naïve children with transfusional iron overload. Eur. J. Haematol. 88, 431–438 (2012).

    Article  CAS  PubMed  Google Scholar 

  69. Panigrahi, I., Vaidya, P. C., Bansal, D. & Marwaha, R. K. Efficacy of deferasirox in North Indian β-thalassemia major patients: a preliminary report. J. Pediatr. Hematol. Oncol. 34, 51–53 (2012).

    Article  CAS  PubMed  Google Scholar 

  70. Gattermann, N. et al. Deferasirox treatment of iron-overloaded chelation-naïve and prechelated patients with myelodysplastic syndromes in medical practice: results from the observational studies eXtend and eXjange. Eur. J. Haematol. 88, 260–268 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Eshghi, P. et al. Efficacy and safety of Iranian made deferasirox (Osveral®) in Iranian major thalassemic patients with transfusional iron overload: A one year prospective multicentric open-label non-comparative study. Daru 19, 240–248 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Chang, H. H. et al. Improved efficacy and tolerability of oral deferasirox by twice-daily dosing for patients with transfusion-dependent β-thalassemia. Pediatr. Blood Cancer 56, 420–424 (2011).

    Article  PubMed  Google Scholar 

  73. Pennell, D. J. et al. A 1-year randomized controlled trial of deferasirox versus deferoxamine for myocardial iron removal in β-thalassemia major (CORDELIA). Blood 123, 1447–1454 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Fernandez-Fernandez, B. et al. Tenofovir nephrotoxicity: 2011 update. AIDS Res. Treat. 2011, 354908 (2011).

    PubMed  PubMed Central  Google Scholar 

  75. Ortiz, A. et al. Tubular cell apoptosis and cidofovir-induced acute renal failure. Antivir. Ther. 10, 185–190 (2005).

    CAS  PubMed  Google Scholar 

  76. Hider, R. C. Charge states of deferasirox-ferric iron complexes. Am. J. Kidney Dis. 55, 614–615 (2010).

    Article  PubMed  Google Scholar 

  77. 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).

    Article  CAS  PubMed  Google Scholar 

  78. Sánchez-González, P. D., López-Hernandez, F. J., Morales, A. I., Macías-Nuñez, J. F. & López-Novoa, J. M. Effects of deferasirox on renal function and renal epithelial cell death. Toxicol. Lett. 203, 154–161 (2011).

    Article  CAS  PubMed  Google Scholar 

  79. Goldstein, D. J. et al. Cyclosporine-associated end-stage nephropathy after cardiac transplantation: incidence and progression. Transplantation 63, 664–668 (1997).

    Article  CAS  PubMed  Google Scholar 

  80. Klein, I. H. et al. Different effects of tacrolimus and cyclosporine on renal hemodynamics and blood pressure in healthy subjects. Transplantation 73, 732–736 (2002).

    Article  CAS  PubMed  Google Scholar 

  81. Oexle, H., Gnaiger, E. & Weiss, G. Iron-dependent changes in cellular energy metabolism: influence on citric acid cycle and oxidative phosphorylation. Biochim. Biophys. Acta 1413, 99–107 (1999).

    Article  CAS  PubMed  Google Scholar 

  82. Gattermann, N. et al. Impact on Iron removal of dose reduction for non-progressive serum creatinine increases during treatment with the once-daily, oral iron chelator deferasirox (Exjade®, ICL670) [abstract]. Blood 108, a3824 (2006).

    Article  CAS  Google Scholar 

  83. Baliga, R., Zhang, Z., Baliga, M., Ueda, N. & Shah, S. V. In vitro and in vivo evidence suggesting a role for iron in cisplatin-induced nephrotoxicity. Kidney Int. 53, 394–401 (1998).

    Article  CAS  PubMed  Google Scholar 

  84. Dixon, S. J. et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell 149, 1060–1072 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Cianciulli, P. et al. Acute renal failure occurring during intravenous desferrioxamine therapy: recovery after haemodialysis. Haematologica 77, 514–515 (1992).

    CAS  PubMed  Google Scholar 

  86. Food and Drug Administration. Safety [online], (2012).

  87. Food and Drug Administration. Safety [online], (2010).

  88. Walker, P. D. & Shah, S. V. Evidence suggesting a role for hydroxyl radical in gentamicin-induced acute renal failure in rats. J. Clin. Invest. 81, 334–341 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Koren, G., Kochavi-Atiya, Y., Bentur, Y. & Olivieri, N. F. The effects of subcutaneous deferoxamine administration on renal function in thalassemia major. Int. J. Hematol. 54, 371–375 (1991).

    CAS  PubMed  Google Scholar 

  90. Clajus, C. et al. Acute kidney injury due to deferoxamine in a renal transplant patient. Nephrol. Dial. Transplant. 23, 1061–1064 (2008).

    Article  PubMed  Google Scholar 

  91. Yoon, Y. S., Byun, H. O., Cho, H., Kim, B. K. & Yoon, G. Complex II defect via down-regulation of iron-sulfur subunit induces mitochondrial dysfunction and cell cycle delay in iron chelation-induced senescence-associated growth arrest. J. Biol. Chem. 278, 51577–51586 (2003).

    Article  CAS  PubMed  Google Scholar 

  92. Justo, P., Lorz, C., Sanz, A., Egido, J. & Ortiz, A. Intracellular mechanisms of cyclosporin A-induced tubular cell apoptosis. J. Am. Soc. Nephrol. 14, 3072–3080 (2003).

    Article  CAS  PubMed  Google Scholar 

  93. Molitoris, B. A. et al. siRNA targeted to p53 attenuates ischemic and cisplatin-induced acute kidney injury. J. Am. Soc. Nephrol. 20, 1754–1764 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Kelly, K. J., Plotkin, Z., Vulgamott, S. L. & Dagher, P. C. P53 mediates the apoptotic response to GTP depletion after renal ischemia-reperfusion: protective role of a p53 inhibitor. J. Am. Soc. Nephrol. 14, 128–138 (2003).

    Article  CAS  PubMed  Google Scholar 

  95. Allon, M., Lawson, L., Eckman, J. R., Delaney, V. & Bourke, E. Effects of nonsteroidal antiinflammatory drugs on renal function in sickle cell anemia. Kidney Int. 34, 500–506 (1988).

    Article  CAS  PubMed  Google Scholar 

  96. Lee, J. W. et al. Pharmacogenetic study of deferasirox, an iron chelating agent. PLoS One 8, e64114 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Lai, M. E. et al. Renal function in patients with β-thalassaemia major: a long-term follow-up study. Nephrol. Dial. Transplant. 27, 3547–3551 (2012).

    Article  CAS  PubMed  Google Scholar 

  98. Han, J. Y. et al. Comprehensive analysis of UGT1A polymorphisms predictive for pharmacokinetics and treatment outcome in patients with non-small-cell lung cancer treated with irinotecan and cisplatin. J. Clin. Oncol. 24, 2237–2244 (2006).

    Article  CAS  PubMed  Google Scholar 

  99. Satoh, T. et al. Genotype-directed, dose-finding study of irinotecan in cancer patients with UGT1A1*28 and/or UGT1A1*6 polymorphisms. Cancer Sci. 102, 1868–1873 (2011).

    Article  CAS  PubMed  Google Scholar 

  100. Shulman, K. et al. Clinical implications of UGT1A1*28 genotype testing in colorectal cancer patients. Cancer 117, 3156–3162 (2011).

    Article  CAS  PubMed  Google Scholar 

  101. Mathijssen, R. H. et al. Clinical pharmacokinetics and metabolism of irinotecan (CPT-11). Clin. Cancer Res. 7, 2182–2194 (2001).

    CAS  PubMed  Google Scholar 

  102. Adams, R. L. & Bird, R. J. Safety and efficacy of deferasirox in the management of transfusion-dependent patients with myelodysplastic syndrome and aplastic anaemia: a perspective review. Ther. Adv. Hematol. 4, 93–102 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Ataga, K. I. & Orringer, E. P. Renal abnormalities in sickle cell disease. Am. J. Hematol. 63, 205–211 (2000).

    Article  CAS  PubMed  Google Scholar 

  104. McKie, K. T. et al. Prevalence, prevention, and treatment of microalbuminuria and proteinuria in children with sickle cell disease. J. Pediatr. Hematol. Oncol. 29, 140–144 (2007).

    Article  CAS  PubMed  Google Scholar 

  105. Vichinsky, E. Clinical application of deferasirox: practical patient management. Am. J. Hematol. 83, 398–402 (2008).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors' research was supported by the grants FIS PS09/00447, PI13/00047, ISCIII-RETIC REDinREN RD12/0021, Comunidad de Madrid S2010/BMD-2378, and CYTED IBERERC, by Programa Intensificación Actividad Investigadora (ISCIII) to A.O., by ERA–EDTA fellowship to L.G.E. and by Programa Interinstitucional para el Fortalecimiento de la Investigación y el Posgrado del Pacífico to J.D.D.-G.

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  1. Escuela Superior de Medicina del Instituto Politécnico Nacional, Avenida Salvador Díaz Mirón s/n, Ciudad de México, 11340, México

    Juan Daniel Díaz-García

  2. IIS-Fundación Jiménez Díaz-UAM, Avenida Reyes Católicos 2, Madrid, 28040, Spain

    Angel Gallegos-Villalobos & Liliana Gonzalez-Espinoza

  3. IDIPAZ, Paseo de la Castellana 261, Madrid, 28046, Spain

    Maria D. Sanchez-Niño

  4. Hospital Ramon y Cajal, Carretera de Colmenar Viejo km. 9,100, Madrid, 28034, Spain

    Jesus Villarrubia

  5. Unidad de Diálisis, Fundación Jiménez Díaz-IRSIN, Avenida Reyes Católicos 2, Madrid, 28040, Spain

    Alberto Ortiz

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Supplementary information

Supplementary Table 1

Diagnostic criteria used to diagnose proximal tubular injury secondary to deferasirox (PDF 105 kb)

Supplementary Table 2

Deferasirox nephrotoxicity in RCTs (PDF 137 kb)

Supplementary Table 3

Deferasirox nephrotoxicity in clinical practice (PDF 154 kb)

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Díaz-García, J., Gallegos-Villalobos, A., Gonzalez-Espinoza, L. et al. Deferasirox nephrotoxicity—the knowns and unknowns. Nat Rev Nephrol 10, 574–586 (2014). https://doi.org/10.1038/nrneph.2014.121

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