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  • Review Article
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Chemotherapy-associated renal dysfunction

Nature Reviews Nephrology volume 5, pages 450–462 (2009)Cite this article

Abstract

The presence of renal dysfunction in a patient receiving chemotherapy can be devastating. Although many patients with cancer have underlying compromised renal function, some chemotherapeutic agents can actually induce renal abnormalities. An understanding of which traditional and newer chemotherapy agents can affect renal function is useful for physicians so that they can monitor patients for renal abnormalities and initiate preventive strategies to minimize renal complications. This Review highlights renal abnormalities associated with current chemotherapy agents and provides suggestions for preventive measures.

Key Points

  • Renal failure in patients with cancer is common and can be devastating

  • Nephrotoxicity develops in one-third of patients on cisplatin, presenting as nonoliguric renal failure, hypomagnesemia, tubular dysfunction, or irreversible renal failure with repeated dosing; volume infusion and amifostine might be protective

  • Ifosfamide causes clinical nephrotoxicity in up to 30% of patients, manifesting as tubular dysfunction and a decreased glomerular filtration rate; hyponatremia and hemorrhagic cystitis are common with cyclophosphamide use

  • The nitrosoureas cause chronic tubulointerstitial nephritis; mitomycin C and gemcitabine can cause hemolytic uremic syndrome, particularly when used in combination with cisplatin or bleomycin

  • Bevacizumab and other newer anti-angiogenesis targeted therapies frequently cause hypertension and proteinuria

  • Managing chemotherapy-related nephrotoxicity involves identifying high-risk patients, adequate volume infusion, detecting nephrotoxicity early, avoiding concurrent use of other nephrotoxic drugs, monitoring renal function, and electrolyte repletion when necessary

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References

  1. Launay-Vacher, V. et al. Lung cancer and renal insufficiency: prevalence and anticancer drug issues. Lung 187, 69–74 (2009).

    Article  PubMed  Google Scholar 

  2. Launay-Vacher, V. et al. Prevalence of renal insufficiency in breast cancer patients and related pharmacological issues. Breast Cancer Res. Treat. doi:10.1007/s10549-008-0131–1.

  3. Ries, F. Nephrotoxicity of chemotherapy. Eur. J. Cancer Clin. Oncol. 24, 951–953 (1988).

    Article  CAS  PubMed  Google Scholar 

  4. Kintzel, P. E. Anticancer drug-induced kidney disorders. Drug Saf. 24, 19–38 (2001).

    Article  CAS  PubMed  Google Scholar 

  5. Choudhury, D. & Ahmed, Z. Drug-associated renal dysfunction and injury. Nat. Clin. Pract. Nephrol. 2, 80–91 (2006).

    Article  CAS  PubMed  Google Scholar 

  6. Glezerman, I., Kris, M. G., Miller, V., Seshan, S. & Flombaum, C. D. Gemcitabine nephrotoxicity and hemolytic uremic syndrome: report of 29 cases from a single institution. Clin. Nephrol. 71, 130–139 (2009).

    Article  CAS  PubMed  Google Scholar 

  7. Duffull, S. B. & Robinson, B. A. Clinical pharmacokinetics and dose optimisation of carboplatin. Clin. Pharmacokinet. 33, 161–183 (1997).

    Article  CAS  PubMed  Google Scholar 

  8. Schilsky, R. L. Renal and metabolic toxicities of cancer chemotherapy. Semin. Oncol. 9, 75–83 (1982).

    CAS  PubMed  Google Scholar 

  9. Taguchi, T., Nazneen, A., Abid, M. R. & Razzaque, M. S. Cisplatin associated nephrotoxicity and pathological events. Contrib. Nephrol. 148, 107–121 (2005).

    Article  CAS  PubMed  Google Scholar 

  10. Winston, J. A. & Safirstein, R. Reduced renal blood flow in early cisplatin-induced acute renal failure in the rat. Am. J. Physiol. 249, F490–F496 (1985).

    Article  CAS  PubMed  Google Scholar 

  11. Launay-Vacher, V. et al. Prevention of cisplatin nephrotoxicity: state of the art and recommendations from the European Society of Clinical Pharmacy Special Interest Group on Cancer Care. Cancer Chemother. Pharmacol. 61, 903–909 (2008).

    Article  CAS  PubMed  Google Scholar 

  12. Meyer, K. B. & Madias, N. E. Cisplatin nephrotoxicity. Miner. Electrolyte Metab. 20, 201–213 (1994).

    CAS  PubMed  Google Scholar 

  13. Santoso, J. T., Lucci, J. A. 3rd, Coleman, R. L., Schafer, I. & Hannigan, E. V. Saline, mannitol, and furosemide hydration in acute cisplatin nephrotoxicity: a randomized trial. Cancer Chemother. Pharmacol. 52, 13–18 (2003).

    Article  CAS  PubMed  Google Scholar 

  14. Townsend, D. M., Deng, M., Zhang, L., Lapus, M. G. & Hanigan, M. H. Metabolism of cisplatin to a nephrotoxin in proximal tubule cells. J. Am. Soc. Nephrol. 14, 1–10 (2003).

    Article  CAS  PubMed  Google Scholar 

  15. Hayes, D. M. et al. High dose cis-platinum diammine dichloride: amelioration of renal toxicity by mannitol diuresis. Cancer 39, 1372–1381 (1977).

    Article  CAS  PubMed  Google Scholar 

  16. Basnakian, A. G. et al. Cisplatin nephrotoxicity is mediated by deoxyribonuclease I. J. Am. Soc. Nephrol. 16, 697–702 (2005).

    Article  CAS  PubMed  Google Scholar 

  17. Ramesh, G. & Reeves, W. B. Salicylate reduces cisplatin nephrotoxicity by inhibition of tumor necrosis factor-α. Kidney Int. 65, 490–499 (2004).

    Article  CAS  PubMed  Google Scholar 

  18. Lam, M. & Adelstein, D. J. Hypomagnesemia and renal magnesium wasting in patients treated with cisplatin. Am. J. Kidney Dis. 8, 164–169 (1986).

    Article  CAS  PubMed  Google Scholar 

  19. Lajer, H. et al. Magnesium depletion enhances cisplatin-induced nephrotoxicity. Cancer Chemother. Pharmacol. 56, 535–542 (2005).

    Article  CAS  PubMed  Google Scholar 

  20. Arany, I. & Safirstein, R. L. Cisplatin nephrotoxicity. Semin. Nephrol. 23, 460–464 (2003).

    Article  CAS  PubMed  Google Scholar 

  21. Cornelison, T. L. & Reed, E. Nephrotoxicity and hydration management for cisplatin, carboplatin, and ormaplatin. Gynecol. Oncol. 50, 147–158 (1993).

    Article  CAS  PubMed  Google Scholar 

  22. Daley-Yates, P. T. & McBrien, D. C. A study of the protective effect of chloride salts on cisplatin nephrotoxicity. Biochem. Pharmacol. 34, 2363–2369 (1985).

    Article  CAS  PubMed  Google Scholar 

  23. Lichtman, S. M. et al. International Society of Geriatric Oncology (SIOG) recommendations for the adjustment of dosing in elderly cancer patients with renal insufficiency. Eur. J. Cancer 43, 14–34 (2007).

    Article  PubMed  Google Scholar 

  24. Raj, G. V., Iasonos, A., Herr, H. & Donat, S. M. Formulas calculating creatinine clearance are inadequate for determining eligibility for cisplatin-based chemotherapy in bladder cancer. J. Clin. Oncol. 24, 3095–3100 (2006).

    Article  CAS  PubMed  Google Scholar 

  25. Kintzel, P. E. & Dorr, R. T. Anticancer drug renal toxicity and elimination: dosing guidelines for altered renal function. Cancer Treat. Rev. 21, 33–64 (1995).

    Article  CAS  PubMed  Google Scholar 

  26. Aronoff, G. R. et al. Drug Prescribing in Renal Failure: Dosing Guidelines for Adults and Children. 5th edn (American College of Physicians, Philadelphia, 2007).

    Google Scholar 

  27. Jackson, A. M. et al. Thrombotic microangiopathy and renal failure associated with antineoplastic chemotherapy. Ann. Intern. Med. 101, 41–44 (1984).

    Article  CAS  PubMed  Google Scholar 

  28. Humphreys, B. D. et al. Gemcitabine-associated thrombotic microangiopathy. Cancer 100, 2664–2670 (2004).

    Article  PubMed  Google Scholar 

  29. Walter, R. B., Joerger, M. & Pestalozzi, B. C. Gemcitabine-associated hemolytic-uremic syndrome. Am. J. Kidney Dis. 40, E16 (2002).

    Article  PubMed  Google Scholar 

  30. Ali, B. H. & Al Moundhri, M. S. Agents ameliorating or augmenting the nephrotoxicity of cisplatin and other platinum compounds: a review of some recent research. Food Chem. Toxicol. 44, 1173–1183 (2006).

    Article  CAS  PubMed  Google Scholar 

  31. Shord, S. S., Thompson, D. M., Krempl, G. A. & Hanigan, M. H. Effect of concurrent medications on cisplatin-induced nephrotoxicity in patients with head and neck cancer. Anticancer Drugs 17, 207–215 (2006).

    Article  CAS  PubMed  Google Scholar 

  32. Fakih, M. Anti-EGFR monoclonal antibody-induced hypomagnesaemia. Lancet Oncol. 8, 366–367 (2007).

    Article  PubMed  Google Scholar 

  33. Asna, N. et al. Time dependent protection of amifostine from renal and hematopoietic cisplatin induced toxicity. Life Sci. 76, 1825–1834 (2005).

    Article  CAS  PubMed  Google Scholar 

  34. Orditura, M. et al. Amifostine: a selective cytoprotective agent of normal tissues from chemo-radiotherapy induced toxicity (Review). Oncology Rep. 6, 1357–1362 (1999).

    CAS  Google Scholar 

  35. Lin, A. & Lawrence, T. S. An anaphylactoid reaction from amifostine. Radiother. Oncol. 79, 352 (2006).

    Article  PubMed  Google Scholar 

  36. Hara, M. et al. Melatonin, a pineal secretory product with antioxidant properties protects against cisplatin-induced nephrotoxicity in rats. J. Pineal Res. 30, 129–138 (2001).

    Article  CAS  PubMed  Google Scholar 

  37. Sener, G. et al. The protective effect of melatonin on cisplatin nephrotoxicity. Fundam. Clin. Pharmacol. 14, 553–560 (2000).

    Article  CAS  PubMed  Google Scholar 

  38. Camargo, S. M., Francescato, H. D., Lavrador, M. A. & Bianchi, M. L. Oral administration of sodium selenite minimizes cisplatin toxicity on proximal tubules of rats. Biol. Trace Elem. Res. 83, 251–262 (2001).

    Article  CAS  PubMed  Google Scholar 

  39. Naziroglu, M., Karaoğlu, A. & Aksoy, A. O. Selenium and high dose vitamin E administration protects cisplatin-induced oxidative damage to renal, liver and lens tissues in rats. Toxicology 195, 221–230 (2004).

    Article  CAS  PubMed  Google Scholar 

  40. Wu, Y. J., Muldoon, L. L. & Neuwelt, E. A. The chemoprotective agent N-acetylcysteine blocks cisplatin-induced apoptosis through caspase signaling pathway. J. Pharmacol. Exp. Ther. 312, 424–431 (2005).

    Article  CAS  PubMed  Google Scholar 

  41. Shimeda, Y. et al. Protective effects of capsaicin against cisplatin induced nephrotoxicity in rats. Biol. Pharm. Bull. 28, 1635–1638 (2005).

    Article  CAS  PubMed  Google Scholar 

  42. Atessahin, A., Yilmaz, S., Karahan, I., Ceribasi, A. O. & Karaoglu, A. Effects of lycopene against cisplatin-induced nephrotoxicity and oxidative stress in rats. Toxicology 212, 116–123 (2005).

    Article  CAS  PubMed  Google Scholar 

  43. Mora Lde, O., Antunes, L. M., Francescato, H. D. & Bianchi Mde, L. The effects of oral glutamine on cisplatin-induced nephrotoxicity in rats. Pharmacol. Res. 47, 517–522 (2003).

    Article  PubMed  CAS  Google Scholar 

  44. Totta, P., Acconcia, F., Leone, S., Cardillo, I. & Marino, M. Mechanisms of naringenin-induced apoptotic cascade in cancer cells: involvement of estrogen receptor α and β signalling. IUBMB Life 56, 491–499 (2004).

    Article  CAS  PubMed  Google Scholar 

  45. Atasoyu, E. M. et al. Investigation of the role of hyperbaric oxygen therapy in cisplatin-induced nephrotoxicity in rats. Arch. Toxicol. 79, 289–293 (2005).

    Article  CAS  PubMed  Google Scholar 

  46. Esposito, M. et al. Effect of the antiarrhythmic drug procainamide on the toxicity and antitumor activity of cis-diamminedichloroplatinum(II). Toxicol. Appl. Pharmacol. 140, 370–377 (1996).

    Article  CAS  PubMed  Google Scholar 

  47. Bagshaw, S. M. & Ghali, W. A. Theophylline for prevention of contrast-induced nephropathy: a systematic review and meta-analysis. Arch. Intern. Med. 165, 1087–1093 (2005).

    Article  PubMed  Google Scholar 

  48. Vesey, D. A. et al. Erythropoietin protects against ischaemic acute renal injury. Nephrol. Dial. Transplant. 19, 348–355 (2004).

    Article  CAS  PubMed  Google Scholar 

  49. McDonald, B. R., Kirmani, S., Vasquez, M. & Mehta, R. L. Acute renal failure associated with the use of intraperitoneal carboplatin. A report of two cases and review of the literature. Am. J. Med. 90, 386–391 (1991).

    Article  CAS  PubMed  Google Scholar 

  50. Labaye, J. et al. Renal toxicity of oxaliplatin. Nephrol. Dial. Transplant. 20, 1275–1276 (2005).

    Article  CAS  PubMed  Google Scholar 

  51. Uehara, T. et al. Nephrotoxicity of a novel antineoplastic platinum complex, nedaplatin: a comparative study with cisplatin in rats. Arch. Toxicol. 79, 451–460 (2005).

    Article  CAS  PubMed  Google Scholar 

  52. Stefanowicz, J. et al. Acute renal failure in paediatric oncological disease [Polish]. Med. Wieku Rozwoj. 11, 337–341 (2007).

    PubMed  Google Scholar 

  53. Butani, L., West, D. C. & Taylor, D. S. End-stage renal disease after high-dose carboplatinum in preparation of autologous stem cell transplantation. Pediatr. Transplant. 7, 408–412 (2003).

    Article  PubMed  Google Scholar 

  54. Pinotti, G. & Martinelli, B. A case of acute tubular necrosis due to oxaliplatin. Ann. Oncol. 13, 1951–1952 (2002).

    Article  CAS  PubMed  Google Scholar 

  55. Kawai, Y., Taniuchi, S., Okahara, S., Nakamura, M. & Gemba, M. Relationship between cisplatin or nedaplatin-induced nephrotoxicity and renal accumulation. Biol. Pharm. Bull. 28, 1385–1388 (2005).

    Article  CAS  PubMed  Google Scholar 

  56. Marzano, C. et al. Antitumor activity of a new platinum(II) complex with low nephrotoxicity and genotoxicity. Chem. Biol. Interact. 148, 37–48 (2004).

    Article  CAS  PubMed  Google Scholar 

  57. Skinner, R., Sharkey, I. M., Pearson, A. D. & Craft, A. W. Ifosfamide, mesna, and nephrotoxicity in children. J. Clin. Oncol. 11, 173–190 (1993).

    Article  CAS  PubMed  Google Scholar 

  58. Rossi, R. Nephrotoxicity of ifosfamide—moving towards understanding the molecular mechanisms. Nephrol. Dial. Transplant. 12, 1091–1092 (1997).

    Article  CAS  PubMed  Google Scholar 

  59. Zhang, J. & Lu, H. Ifosfamide induces acute renal failure via inhibition of the thioredoxin reductase activity. Free Radic. Biol. Med. 43, 1574–1583 (2007).

    Article  CAS  PubMed  Google Scholar 

  60. Skinner, R. et al. Risk factors for ifosfamide nephrotoxicity in children. Lancet 348, 578–580 (1996).

    Article  CAS  PubMed  Google Scholar 

  61. Lee, B. S. et al. Ifosfamide nephrotoxicity in pediatric cancer patients. Pediatr. Nephrol. 16, 796–799 (2001).

    Article  CAS  PubMed  Google Scholar 

  62. Pratt, C. B. et al. Ifosfamide, Fanconi's syndrome, and rickets. J. Clin. Oncol. 9, 1495–1499 (1991).

    Article  CAS  PubMed  Google Scholar 

  63. Husband, D. J. & Watkin, S. W. Fatal hypokalemia associated with ifosfamide/mesna chemotherapy. Lancet 1, 1116 (1988).

    Article  CAS  PubMed  Google Scholar 

  64. Skinner, R. Chronic Ifosfamide nephrotoxicity in children. Med. Pediatr. Oncol. 41, 190–197 (2003).

    Article  CAS  PubMed  Google Scholar 

  65. Prasad, V. K. et al. Progressive glomerular toxicity of ifosfamide in children. Med. Pediatr. Oncol. 27, 149–155 (1996).

    Article  CAS  PubMed  Google Scholar 

  66. Skinner, R., Cotterill, S. J. & Stevens, M. C. Risk factors for nephrotoxicity after ifosfamide treatment in children: a UKCCSG Late Effects Group study. United Kingdom Children's Cancer Study Group. Br. J. Cancer 82, 1636–1645 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Aleksa, K., Woodland, C. & Koren, G. Young age and the risk for ifosfamide-induced nephrotoxicity: a critical review of two opposing studies. Pediatr. Nephrol. 16, 1153–1158 (2001).

    Article  CAS  PubMed  Google Scholar 

  68. Nissim, I. & Weinberg, J. M. Glycine attenuates Fanconi syndrome induced by maleate and ifosfamide in rats. Kidney Int. 49, 684–695 (1996).

    Article  CAS  PubMed  Google Scholar 

  69. Schlenzig, J. S. et al. L-carnitine: a way to decrease cellular toxicity of ifosfamide? Eur. J. Pediatr. 154, 686–687 (1995).

    Article  CAS  PubMed  Google Scholar 

  70. Aleksa, K., Halachmi, N., Ito, S. & Koren, G. A tubule cell model for ifosfamide nephrotoxicity. Can. J. Physiol. Pharmacol. 83, 499–408 (2005).

    Article  CAS  PubMed  Google Scholar 

  71. Sener, G. et al. Melatonin attenuates ifosfamide-induced Fanconi syndrome in rats. J. Pineal Res. 37, 17–25 (2004).

    Article  CAS  PubMed  Google Scholar 

  72. Bressler, R. B. & Huston, D. P. Water intoxication following moderate dose intravenous cyclophosphamide. Arch. Intern. Med. 145, 548–549 (1985).

    Article  CAS  PubMed  Google Scholar 

  73. Cornwell, G. 3rd, Pajak, T. F., McIntyre, O. R., Kochwa, S. & Dosik, H. Influence of renal failure on the myelosuppressive effects of melphalan: cancer and leukemia group B experience. Cancer Treat Rep. 66, 475–481 (1982).

    PubMed  Google Scholar 

  74. Zwaveling, J. H. et al. Renal function in cancer patients treated with hyperthermic isolated limb perfusion with recombinant tumor necrosis factor alpha and melphalan. Nephron 76, 146–152 (1997).

    Article  CAS  PubMed  Google Scholar 

  75. Kashimura, M., Kondo, M., Abe, T., Shinohara, M. & Baba, S. A case report of acute renal failure induced by melphalan in a patient with ovarian cancer [Japanese]. Gan No Rinsho 34, 2015–2018 (1988).

    CAS  PubMed  Google Scholar 

  76. Leung, N. et al. Acute renal insufficiency after high-dose melphalan in patients with primary systemic amyloidosis during stem cell transplantation. Am. J. Kidney Dis. 45, 102–111 (2005).

    Article  CAS  PubMed  Google Scholar 

  77. Devine, S. M. et al. Fludarabine and melphalan-based conditioning for patients with advanced hematological malignancies relapsing after a previous hematopoietic stem cell transplant. Bone Marrow Transplant. 28, 557–562 (2001).

    Article  CAS  PubMed  Google Scholar 

  78. Weiss, R. B. Streptozocin: a review of its pharmacology, efficacy, and toxicity. Cancer Treat. Rep. 66, 427–438 (1982).

    CAS  PubMed  Google Scholar 

  79. Micetich, K. C., Jensen-Akula, M., Mandard, J. C. & Fisher, R. I. Nephrotoxicity of semustine (methyl-CCNU) in patients with malignant melanoma receiving adjuvant chemotherapy. Am. J. Med. 71, 967–972 (1981).

    Article  CAS  PubMed  Google Scholar 

  80. De Vita, V. T. et al. Clinical trials with 1,3-bis (2-chloroethyl)-1-nitrosourea, NSC-409962. Cancer Res. 25, 1876–1881 (1965).

    CAS  PubMed  Google Scholar 

  81. Kramer, R., McMenamin, M. G. & Boyd, M. R. In vivo studies on the relationship between hepatic metabolism and the renal toxicity of 1-(2-chloroethyl)-3-(trans-4-methylycyclohexyl)-1-nitrosourea (MeCCNU). Toxicol. Appl. Pharmacol. 85, 221–230 (1986).

    Article  CAS  PubMed  Google Scholar 

  82. Weiss, R. B., Posada, J. G. Jr, Kramer, R. A. & Boyd, M. R. Nephrotoxicity of semustine. Cancer Treat. Rep. 67, 1105–1112 (1983).

    CAS  PubMed  Google Scholar 

  83. Delaney, V., de Pertuz, Y., Nixon, D. & Bourke, E. Indomethacin in streptozocin-induced nephrogenic diabetes insipidus. Am. J. Kidney Dis. 9, 79–83 (1987).

    Article  CAS  PubMed  Google Scholar 

  84. Harrison, S. D. Jr, Cox, J. L. & Giles, R. C. Jr. Effects of prochlorperazine on experimental nephrotoxicity. Cancer Chemother. Pharmacol. 10, 62–67 (1982).

    Article  CAS  PubMed  Google Scholar 

  85. Cantrell, J. E. Jr, Phillips, T. M. & Schein, P. S. Carcinoma-associated hemolytic-uremic syndrome: a complication of mitomycin C chemotherapy. J. Clin. Oncol. 3, 723–734 (1985).

    Article  PubMed  Google Scholar 

  86. Lesesne, J. B. et al. Cancer-associated hemolytic-uremic syndrome: analysis of 85 cases from a national registry. J. Clin. Oncol. 7, 781–789 (1989).

    Article  CAS  PubMed  Google Scholar 

  87. Poch, E., Almirall, J., Nicolas, J. M., Torras, A. & Revert, L. Treatment of mitomycin-C-associated hemolytic uremic syndrome with plasmapheresis. Nephron 55, 89–90 (1990).

    Article  CAS  PubMed  Google Scholar 

  88. Snyder, H. W. Jr et al. Treatment of cancer chemotherapy-associated thrombotic thrombocytopenic purpura/hemolytic uremic syndrome by protein A immunoadsorption of plasma. Cancer 71, 1882–1892 (1993).

    Article  PubMed  Google Scholar 

  89. Gordon, L. I. & Kwaan, H. C. Thrombotic microangiopathy manifesting as thrombotic thrombocytopenic purpura/hemolytic uremic syndrome in the cancer patient. Semin. Thromb. Hemost. 25, 217–221 (1999).

    Article  CAS  PubMed  Google Scholar 

  90. Kennedy, B. J. Metabolic and toxic effects of mithramycin during tumor therapy. Am. J. Med. 49, 494–503 (1970).

    Article  CAS  PubMed  Google Scholar 

  91. Benedetti, R. G., Heilman, K. J. 3rd, Gabow, P. A. Nephrotoxicity following single dose mithramycin therapy. Am. J. Nephrol. 3, 277–278 (1983).

    Article  CAS  PubMed  Google Scholar 

  92. Peterson, B. A., Collins, A. J., Vogelzang, N. J. & Bloomfield, C. D. 5-azacytidine and renal tubular dysfunction. Blood 57, 182–185 (1981).

    Article  CAS  PubMed  Google Scholar 

  93. Fung, M. C. et al. A review of hemolytic uremic syndrome in patients treated with gemcitabine therapy. Cancer 85, 2023–2032 (1999).

    Article  CAS  PubMed  Google Scholar 

  94. Balis, F. M. Pharmacokinetic drug interactions of commonly used anticancer drugs. Clin. Pharmacokinet. 11, 223–235 (1986).

    Article  CAS  PubMed  Google Scholar 

  95. Cetiner, M. et al. Taurine protects against methotrexate-induced toxicity and inhibits leukocyte death. Toxicol. Appl. Pharmacol. 209, 39–50 (2005).

    Article  CAS  PubMed  Google Scholar 

  96. Abelson, H. T. et al. Methotrexate-induced renal impairment: clinical studies and rescue from systemic toxicity with high-dose leucovorin and thymidine. J. Clin. Oncol. 1, 208–216 (1983).

    Article  CAS  PubMed  Google Scholar 

  97. Widemann, B. C. et al. High-dose methotrexate-induced nephrotoxicity in patients with osteosarcoma. Cancer 100, 2222–2232 (2004).

    Article  CAS  PubMed  Google Scholar 

  98. Widemann, B. C. & Adamson, P. C. Understanding and managing methotrexate nephrotoxicity. Oncologist 11, 694–703 (2006).

    Article  CAS  PubMed  Google Scholar 

  99. Albrecht, A. M., Boldizsar, E. & Hutchison, D. J. Carboxypeptidase displaying differential velocity in hydrolysis of methotrexate, 5-methyltetrahydrofolic acid, and leucovorin. J. Bacteriol. 134, 506–513 (1978).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Margolis, J. & Grever, M. R. Pentostatin (Nipent): a review of potential toxicity and its management. Semin. Oncol. 27 (Suppl. 5), 9–14 (2000).

    CAS  PubMed  Google Scholar 

  101. Grever, M. R., Bisaccia, E., Scarborough, D. A., Metz, E. N. & Neidhart, J. A. An investigation of 2'-deoxycoformycin in the treatment of cutaneous T-cell lymphoma. Blood 61, 279–282 (1983).

    Article  CAS  PubMed  Google Scholar 

  102. Guleria, A. S. et al. Renal dysfunction associated with the administration of high-dose interleukin-2 in 199 consecutive patients with metastatic melanoma or renal cell carcinoma. J. Clin. Oncol. 12, 2714–2722 (1994).

    Article  CAS  PubMed  Google Scholar 

  103. Geertsen, P. F. et al. Renal haemodynamics, sodium and water reabsorption during continuous intravenous infusion of recombinant interleukin-2. Clin. Sci. (Lond.) 95, 73–81 (1998).

    Article  CAS  Google Scholar 

  104. Mercatello, A. et al. Acute renal failure with preserved renal plasma flow induced by cancer immunotherapy. Kidney Int. 40, 309–314 (1991).

    Article  CAS  PubMed  Google Scholar 

  105. Belldegrun, A. et al. Effects of interleukin-2 on renal function in patients receiving immunotherapy for advanced cancer. Ann. Intern. Med. 106, 817–822 (1987).

    Article  CAS  PubMed  Google Scholar 

  106. Avarbock, A. B. et al. Lethal vascular leak syndrome after denileukin diftitox administration to a patient with cutaneous gamma/delta T-cell lymphoma and occult cirrhosis. Am. J. Hematol. 83, 593–595 (2008).

    Article  CAS  PubMed  Google Scholar 

  107. Foss, F. Clinical experience with denileukin diftitox (ONTAK). Semin. Oncol. 33 (Suppl. 3), S11–S16 (2006).

    Article  CAS  PubMed  Google Scholar 

  108. Quesada, J. R., Talpaz, M., Rios, A., Kurzrock, R. & Gutterman, J. U. Clinical toxicity of interferons in cancer patients: a review. J. Clin. Oncol. 4, 234–243 (1986).

    Article  CAS  PubMed  Google Scholar 

  109. Selby, P., Kohn, J., Raymond, J., Judson, I. & McElwain, T. Nephrotic syndrome during treatment with interferon. Br. Med. J. (Clin. Res. Ed.) 290, 1180 (1985).

    Article  CAS  Google Scholar 

  110. Willson, R. A. Nephrotoxicity of interferon alfa-ribavirin therapy for chronic hepatitis C. J. Clin. Gastroenterol. 35, 89–92 (2002).

    Article  CAS  PubMed  Google Scholar 

  111. Nair, S. et al. Interferon-induced reversible acute renal failure with nephrotic syndrome. Urology 39, 169–172 (1992).

    Article  CAS  PubMed  Google Scholar 

  112. Zuber, J. et al. Alpha-interferon-associated thrombotic microangiopathy: a clinicopathologic study of 8 patients and review of the literature. Medicine (Baltimore) 81, 321–331 (2002).

    Article  CAS  Google Scholar 

  113. Dimopoulos, M. A., Kastritis, E., Rosinol, L., Bladé, J. & Ludwig, H. Pathogenesis and treatment of renal failure in multiple myeloma. Leukemia 22, 1485–1493 (2008).

    Article  CAS  PubMed  Google Scholar 

  114. Andritsos, L. A. et al. Higher doses of lenalidomide are associated with unacceptable toxicity including life-threatening tumor flare in patients with chronic lymphocytic leukemia. J. Clin. Oncol. 26, 2519–2525 (2008).

    Article  CAS  PubMed  Google Scholar 

  115. Tosi, P. et al. Thalidomide alone or in combination with dexamethasone in patients with advanced, relapsed or refractory multiple myeloma and renal failure. Eur. J. Haematol. 73, 98–103 (2004).

    Article  CAS  PubMed  Google Scholar 

  116. Ludwig, H., Drach, J., Graf, H., Lang, A. & Meran, J. G. Reversal of acute renal failure by bortezomib-based chemotherapy in patients with multiple myeloma. Haematologica 92, 1411–1414 (2007).

    Article  CAS  PubMed  Google Scholar 

  117. Izzedine, H., Rixe, O., Billemont, B., Baumelou, A. & Deray, G. Angiogenesis inhibitor therapies: focus on kidney toxicity and hypertension. Am. J. Kidney Dis. 50, 203–218 (2007).

    Article  CAS  PubMed  Google Scholar 

  118. Zhu, X., Wu, S., Dahut, W. L. & Parikh, C. R. Risks of proteinuria and hypertension with bevacizumab, an antibody against vascular endothelial growth factor: systematic review and meta-analysis. Am. J. Kidney Dis. 49, 186–193 (2007).

    Article  CAS  PubMed  Google Scholar 

  119. Widakowich, C., de Castro, G. Jr, de Azambuja, E., Dinh, P. & Awada, A. Review: side effects of approved molecular targeted therapies in solid cancers. Oncologist 12, 1443–1455 (2007).

    Article  CAS  PubMed  Google Scholar 

  120. Hood, J. D., Meininger, C. J., Ziche, M. & Granger, H. J. VEGF upregulates ecNOS message, protein, and NO production in human endothelial cells. Am. J. Physiol. 274, H1054–H1058 (1998).

    CAS  PubMed  Google Scholar 

  121. Stokes, M. B., Erazo, M. C. & D'Agati, V. D. Glomerular disease related to anti-VEGF therapy. Kidney Int. 74, 1487–1491 (2008).

    Article  CAS  PubMed  Google Scholar 

  122. Eremina, V. et al. VEGF inhibition and renal thrombotic microangiopathy. N. Engl. J. Med. 358, 1129–1136 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. George, B. A., Zhou, X. J. & Toto, R. Nephrotic syndrome after bevacizumab: case report and literature review. Am. J. Kidney Dis. 49, e23–e29 (2007).

    Article  PubMed  Google Scholar 

  124. Johnson, D. H. et al. Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small cell lung cancer. J. Clin. Oncol. 22, 2184–2191 (2004).

    Article  CAS  PubMed  Google Scholar 

  125. Miller, K. D. et al. Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J. Clin. Oncol. 23, 792–799 (2005).

    Article  CAS  PubMed  Google Scholar 

  126. Schrag, D. et al. Cetuximab therapy and symptomatic hypomagnesemia. J. Natl Cancer Inst. 97, 1221–1224 (2005).

    Article  CAS  PubMed  Google Scholar 

  127. Muallem, S. & Moe, O. W. When EGF is offside, magnesium is wasted. J. Clin. Invest. 117, 2086–2069 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Van Cutsem, E. et al. Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J. Clin. Oncol. 25, 1658–1664 (2007).

    Article  CAS  PubMed  Google Scholar 

  129. Izzedine, H., Brocheriou, I., Deray, G. & Rixe, O. Thrombotic microangiopathy and anti-VEGF agents. Nephrol. Dial. Transplant. 22, 1481–1482 (2007).

    Article  PubMed  Google Scholar 

  130. Wan, H. L. & Yao, N. S. Acute renal failure associated with gefitinib therapy. Lung 184, 249–250 (2006).

    Article  PubMed  Google Scholar 

  131. Kumasaka, R. et al. Side effects of the therapy: case 1. Nephrotic syndrome associated with gefitinib therapy. J. Clin. Oncol. 22, 2504–2505 (2004).

    Article  PubMed  Google Scholar 

  132. Foringer, J. R. et al. Acute renal failure secondary to imatinib mesylate treatment in prostate cancer. Ann. Pharmacother. 39, 2136–2138 (2005).

    Article  PubMed  Google Scholar 

  133. Kitiyakara, C. & Atichartakarn, V. Renal failure associated with a specific inhibitor of BCR-ABL tyrosine kinase, STI 571. Nephrol. Dial. Transplant. 17, 685–687 (2002).

    Article  PubMed  Google Scholar 

  134. François, H. et al. Partial Fanconi syndrome induced by imatinib therapy: a novel cause of urinary phosphate loss. Am. J. Kidney Dis. 51, 298–301 (2008).

    Article  PubMed  CAS  Google Scholar 

  135. Al Aly, Z. Philoctête Ashley, J. M., Gellens, M. E. & González, E. A. Thrombotic thrombocytopenic purpura in a patient treated with imatinib mesylate: True association or mere coincidence? Am. J. Kidney Dis. 45, 762–768 (2005).

    Article  PubMed  Google Scholar 

  136. Holstein, S. A., Stokes, J. B. & Hohl, R. J. Renal failure and recovery associated with second-generation Bcr-Abl kinase inhibitors in imatinib-resistant chronic myelogenous leukemia. Leuk. Res. 33, 344–347 (2009).

    Article  CAS  PubMed  Google Scholar 

  137. Wu, S., Chen, J. J., Kudelka, A., Lu, J. & Zhu, X. Incidence and risk of hypertension with sorafenib in patients with cancer: a systematic review and meta-analysis. Lancet Oncol. 9, 86–87 (2008).

    Article  CAS  Google Scholar 

  138. Zhu, X., Stergiopoulos, K. & Wu, S. Risk of hypertension and renal dysfunction with an angiogenesis inhibitor sunitinib: systematic review and meta-analysis. Acta Oncol. 48, 9–17 (2009).

    Article  CAS  PubMed  Google Scholar 

  139. Patel, T. V. et al. A preeclampsia-like syndrome characterized by reversible hypertension and proteinuria induced by the multitargeted kinase inhibitors sunitinib and sorafenib. J. Natl Cancer Inst. 100, 282–284 (2008).

    Article  CAS  PubMed  Google Scholar 

  140. Bollée, G. et al. Thrombotic microangiopathy secondary to VEGF pathway inhibition by sunitinib. Nephrol. Dial. Transplant. 24, 682–685 (2009).

    Article  PubMed  CAS  Google Scholar 

  141. Kapiteijn, E., Brand, A., Kroep, J. & Gelderblom, H. Sunitinib induced hypertension, thrombotic microangiopathy and reversible posterior leukencephalopathy syndrome. Ann. Oncol. 18, 1745–1747 (2007).

    Article  CAS  PubMed  Google Scholar 

  142. Zojer, N., Keck, A. V. & Pecherstorfer, M. Comparative tolerability of drug therapies for hypercalcaemia of malignancy. Drug Saf. 21, 389–406 (1999).

    Article  CAS  PubMed  Google Scholar 

  143. Markowitz, G. S. et al. Collapsing focal segmental glomerulosclerosis following treatment with high-dose pamidronate. J. Am. Soc. Nephrol 12, 1164–1172 (2001).

    Article  CAS  PubMed  Google Scholar 

  144. Markowitz, G. S. et al. Toxic acute tubular necrosis following treatment with zoledronate (Zometa). Kidney Int. 64, 281–289 (2003).

    Article  CAS  PubMed  Google Scholar 

  145. Henrich, D., Hoffmann, M., Uppenkamp, M. & Bergner, R. Ibandronate for the treatment of hypercalcemia or nephrocalcinosis in patients with multiple myeloma and acute renal failure: Case reports. Acta Haematol. 116, 165–172 (2006).

    Article  CAS  PubMed  Google Scholar 

  146. Kyle, R. A. et al. American Society of Clinical Oncology 2007 clinical practice guideline update on the role of bisphosphonates in multiple myeloma. J. Clin. Oncol. 25, 2464–2472 (2007).

    Article  CAS  PubMed  Google Scholar 

  147. Mann, B. S., Johnson, J. R., Cohen, M. H., Justice, R. & Pazdur, R. FDA approval summary: vorinostat for treatment of advanced primary cutaneous T-cell lymphoma. Oncologist 12, 1247–1252 (2007).

    Article  CAS  PubMed  Google Scholar 

  148. Altman, A. Acute tumor lysis syndrome. Semin. Oncol. 28 (Suppl. 5), 3–8 (2001).

    Article  CAS  PubMed  Google Scholar 

  149. Goldman, S. C. et al. A randomized comparison between rasburicase and allopurinol in children with lymphoma or leukemia at high risk for tumor lysis. Blood 97, 2998–3003 (2001).

    Article  CAS  PubMed  Google Scholar 

  150. Gomez, G. A., Stutzman, L. & Chu, T. M. Xanthine nephropathy during chemotherapy in deficiency of hypoxanthine-guanine phosphoribosyltransferase. Arch. Intern. Med. 138, 1017–1019 (1978).

    Article  CAS  PubMed  Google Scholar 

  151. Hutcherson, D. A., Gammon, D. C., Bhatt, M. S. & Faneuf, M. Reduced-dose rasburicase in the treatment of adults with hyperuricemia associated with malignancy. Pharmacotherapy 26, 242–247 (2006).

    Article  CAS  PubMed  Google Scholar 

  152. Coiffier, B., Altman, A., Pui, C. H., Younes, A. & Cairo, M. S. Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based review. J. Clin. Oncol. 26, 2767–2778 (2008).

    Article  CAS  PubMed  Google Scholar 

  153. Holdsworth, M. T. & Nguyen, P. Role of i.v. allopurinol and rasburicase in tumor lysis syndrome. Am. J. Health Syst. Pharm. 60, 2213–2222 (2003).

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Drexel University College of Medicine, Philadelphia, PA, USA

    Vaibhav Sahni & Ziauddin Ahmed

  2. Veterans Affairs North Texas Health Care System, Dallas, TX, USA

    Devasmita Choudhury

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  1. Vaibhav Sahni
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Sahni, V., Choudhury, D. & Ahmed, Z. Chemotherapy-associated renal dysfunction. Nat Rev Nephrol 5, 450–462 (2009). https://doi.org/10.1038/nrneph.2009.97

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