American Journal of Kidney Diseases
Volume 50, Issue 2 , Pages 203-218 , August 2007

Angiogenesis Inhibitor Therapies: Focus on Kidney Toxicity and Hypertension

  • Hassane Izzedine, MD, PhD

      Affiliations

    • Department of Nephrology, Pitie-Salpetriere Hospital, Paris, France
    • Corresponding Author InformationAddress correspondence to Hassane Izzedine, MD, PhD, Department of Nephrology, La Pitié-Salpêtrière Hospital, 47-80 Boulevard de l’Hôpital, Assistance Publique-Hopitaux de Paris, Pierre et Marie Curie University, 75013 Paris, France.
    • ,
  • Olivier Rixe, MD, PhD

      Affiliations

    • Department of Medical Oncology, Pitie-Salpetriere Hospital, Paris, France.
    • ,
  • Bertrand Billemont, MD

      Affiliations

    • Department of Medical Oncology, Pitie-Salpetriere Hospital, Paris, France.
    • ,
  • Alain Baumelou, MD

      Affiliations

    • Department of Nephrology, Pitie-Salpetriere Hospital, Paris, France
    • ,
  • Gilbert Deray, MD

      Affiliations

    • Department of Nephrology, Pitie-Salpetriere Hospital, Paris, France

Received 19 December 2006 ,Accepted 24 April 2007.

References 

  1. Ferrara N. The role of vascular endothelial growth factor in pathological angiogenesis. Breast Cancer Res Treat. 1995;36:127–137
  2. Lin NU, Winer EP. New targets for therapy in breast cancer: Small molecule tyrosine kinase inhibitors. Breast Cancer Res. 2004;6:204–210
  3. Emens LA, Davidson NE. Trastuzumab in breast cancer. Oncology (Huntingt). 2004;18:1117–1128
  4. Roy-Chaudhury P, Jones MC, MacLeod AM, Haites NE, Simpson JG, Power DA. An immunohistological study of epidermal growth factor receptor and neu receptor and neu receptor expression in proliferative glomerulonephritis. Pathology. 1993;25:327–332
  5. Sargent ER, Gomella LG, Belldegrun A, Linehan WM, Kasid A. Epidermal growth factor receptor gene expression in normal human kidney and renal cell carcinoma. J Urol. 1989;142:1364–1368
  6. Nakopoulou L, Stefanaki K, Boletis J, et al. Immunohistochemical study of epidermal growth factor receptor (EGFR) in various types of renal injury. Nephrol Dial Transplant. 1994;9:764–769
  7. Yoshioka K, Takemura T, Murakami K, et al. Identification and localization of epidermal growth factor and its receptor in the human glomerulus. Lab Invest. 1990;63:189–196
  8. Folkman J. Tumor angiogenesis. Adv Cancer Res. 1974;19:331–358
  9. Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med. 2003;9:669–676
  10. Houck KA, Ferrara N, Winer J, Cachianes G, Li B, Leung DW. The vascular endothelial growth factor family: Identification of a fourth molecular species and characterization of alternative splicing of RNA. Mol Endocrinol. 1991;5:1806–1814
  11. Tischer E, Mitchell R, Hartman T, et al. The human gene for vascular endothelial growth factor (Multiple protein forms are encoded through alternative exon splicing). J Biol Chem. 1991;266:11947–11954
  12. Ferrara N. Molecular and biological properties of vascular endothelial growth factor. J Mol Med. 1999;77:527–543
  13. Kamba T, Tam BY, Hashizume H, et al. VEGF-dependent plasticity of fenestrated capillaries in the normal adult microvasculature. Am J Physiol Heart Circ Physiol. 2006;290:H560–H576
  14. Eremina V, Sood M, Haigh J, et al. Glomerular-specific alterations of VEGF-A expression lead to distinct congenital and acquired renal diseases. J Clin Invest. 2003;111:707–716
  15. Mattot V, Moons L, Lupu F, et al. Loss of the VEGF(164) and VEGF(188) isoforms impairs postnatal glomerular angiogenesis and renal arteriogenesis in mice. J Am Soc Nephrol. 2002;13:1548–1560
  16. Thomas S, Vanuystel J, Gruden G, et al. Vascular endothelial growth factor receptors in human mesangium in vitro and in glomerular disease. J Am Soc Nephrol. 2000;11:1236–1243
  17. Sugimoto H, Hamano Y, Charytan D, et al. Neutralization of circulating vascular endothelial growth factor (VEGF) by anti-VEGF antibodies and soluble VEGF receptor 1 (sFlt-1) induces proteinuria. J Biol Chem. 2003;278:12605–12608
  18. Yang JC, Haworth L, Sherry RM, et al. A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med. 2003;349:427–434
  19. Cunningham D, Humblet Y, Siena S, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med. 2004;351:337–345
  20. Bonner JA, Harari PM, Giralt J, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006;354:567–578
  21. Baselga J, Pfister D, Cooper MR, et al. Phase I studies of anti-epidermal growth factor receptor chimeric antibody C225 alone and in combination with cisplatin. J Clin Oncol. 2000;18:904–914
  22. Harari PM. Epidermal growth factor receptor inhibition strategies in oncology. Endocr Relat Cancer. 2004;11:689–708
  23. Vidal: Herceptin (ed 82). 2006, pp 962-964. Available at: www.vidal.fr. Accessed: January 15, 2007
  24. Jensen BV. Cardiotoxic consequences of anthracycline-containing therapy in patients with breast cancer. Semin Oncol. 2006;33(suppl 15):S15–S21
  25. Druker BJ, Tamura S, Buchdunger E, et al. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med. 1996;2:561–566
  26. Joensuu H, Roberts PJ, Sarlomo-Rikala M, et al. Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor. N Engl J Med. 2001;344:1052–1056
  27. Kilic T, Alberta JA, Zdunek PR, et al. Intracranial inhibition of platelet-derived growth factor-mediated glioblastoma cell growth by an orally active kinase inhibitor of the 2-phenylaminopyrimidine class. Cancer Res. 2000;60:5143–5150
  28. Sjoblom T, Shimizu A, O’Brien KP, et al. Growth inhibition of dermatofibrosarcoma protuberans tumors by the platelet-derived growth factor receptor antagonist STI571 through induction of apoptosis. Cancer Res. 2001;61:5778–5783
  29. Gleich GJ, Leiferman KM, Pardanani A, Tefferi A, Butterfield JH. Treatment of hypereosinophilic syndrome with imatinib mesilate. Lancet. 2002;359:1577–1578
  30. Cools J, de Angelo DJ, Gotlib J, et al. A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome. N Engl J Med. 2003;348:1201–1214
  31. Pardanani A, Ketterling RP, Brockman SR, et al. CHIC2 deletion, a surrogate for FIP1L1-PDGFRA fusion, occurs in systemic mastocytosis associated with eosinophilia and predicts response to imatinib mesylate therapy. Blood. 2003;102:3093–3096
  32. Kitiyakara C, Atichartakarn V. Renal failure associated with a specific inhibitor of BCR-ABL tyrosine kinase, STI 571. Nephrol Dial Transplant. 2002;17:685–687
  33. Pou M, Saval N, Vera M, et al. Acute renal failure secondary to imatinib mesylate treatment in chronic myeloid leukemia. Leuk Lymphoma. 2003;44:1239–1241
  34. Al Aly Z, Philoctete Ashley JM, Gellens ME, Gonzalez EA. Thrombotic thrombocytopenic purpura in a patient treated with imatinib mesylate: True association or mere coincidence?. Am J Kidney Dis. 2005;45:762–768
  35. Foringer JR, Verani RR, Tjia VM, Finkel KW, Samuels JA, Guntupalli JS. Acute renal failure secondary to imatinib mesylate treatment in prostate cancer. Ann Pharmacother. 2005;39:2136–2138
  36. Ranson M, Wardell S. Gefitinib, a novel, orally administered agent for the treatment of cancer. J Clin Pharm Ther. 2004;29:95–103
  37. Roskoski R. The ErbB/HER receptor proteintyrosine kinases and cancer. Biochem Biophys Res Commun. 2004;319:1–11
  38. Baselga J, Averbuch SD. ZD1839 (‘Iressa’) as an anticancer agent. Drugs. 2000;60(suppl 1):S33–S40
  39. Inomata S, Takahashi H, Nagata M, et al. Acute lung injury as an adverse event of gefitinib. Anticancer Drugs. 2004;15:461–467
  40. Kumasaka R, Nakamura N, Shirato K, et al. Side effects of the therapy: Case 1 (Nephrotic syndrome associated with gefitinib therapy). J Clin Oncol. 2004;22:2504–2505
  41. Wan HL, Yao NS. Acute renal failure associated with gefitinib therapy. Lung. 2006;184:249–250
  42. Moyer JD, Barbacci EG, Iwata KK, et al. Induction of apoptosis and cell cycle arrest by CP-358,774, an inhibitor of epidermal growth factor receptor tyrosine kinase. Cancer Res. 1997;57:4838–4848
  43. Iwata K, Provoncha K, Gibson N: Inhibition of mutant EGFRvIII transformed cells by tyrosine kinase inhibitor OSI-774 (Tarceva) [abstract 79]. Presented at the Annual Meeting of the American Society of Clinical Oncology, Orlando, 2002
  44. Grunwald V, Hidalgo M. Development of the epidermal growth factor receptor inhibitor OSI-774. Semin Oncol. 2003;30:23–31
  45. Herbst RS, Johnson DH, Mininberg E, et al. Phase I/II trial evaluating the anti-vascular endothelial growth factor monoclonal antibody bevacizumab in combination with the HER-1/epidermal growth factor receptor tyrosine kinase inhibitor erlotinib for patients with recurrent non-small-cell lung cancer. J Clin Oncol. 2005;23:2544–2555
  46. Zhu X, Wu S, Dahut WL, Parikh CR. Risks of proteinuria and hypertension with bevacizumab, an antibody against vascular endothelial growth factor: Systematic review and meta-analysis. Am J Kidney Dis. 2007;49:186–193
  47. Johnson DH, Fehrenbacher L, Novotny WF. 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. 2004;22:2184–2191
  48. Miller KD, Chap LI, Holmes FA. Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol. 2005;23:792–799
  49. George BA, Zhou XJ, Toto R. Nephrotic syndrome after bevacizumab: Case report and literature review. Am J Kidney Dis. 2007;49:23–29
  50. Faivre S, Delbaldo C, Vera K, et al. Safety, pharmacokinetic, and antitumor activity of SU11248, a novel oral multitarget tyrosine kinase inhibitor, in patients with cancer. J Clin Oncol. 2006;24:25–35
  51. Motzer RJ, Michaelson MD, Redman BG, et al. Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma. J Clin Oncol. 2006;24:16–24
  52. Ratain MJ, Eisen T, Stadler WM, et al. Phase II placebo-controlled randomized discontinuation trial of sorafenib in patients with metastatic renal cell carcinoma. J Clin Oncol. 2006;24:2505–2512
  53. Veronese ML, Mosenkis A, Flaherty KT, et al. Mechanisms of hypertension associated with BAY 43-9006. J Clin Oncol. 2006;24:1363–1369
  54. Escudier B, Szczylik C, Eisen T, et al: Randomized phase III trial of the Raf kinase and VEGFR inhibitor sorafenib (BAY 43-9006) in patients with advanced renal cell carcinoma (RCC). J Clin Oncol 2005 Annual Meeting Proceedings Part I 23(16S), 2005 (June 1 Suppl) (abstr 4510)
  55. Rugo HS, Herbst RS, Liu G, et al. Phase I trial of the oral antiangiogenesis agent AG-013736 in patients with advanced solid tumors: Pharmacokinetic and clinical results. J Clin Oncol. 2005;23:5474–5483
  56. Rini B, Rixe O, Bukowski R, et al. AG-013736, a multitarget tyrosine kinase receptor inhibitor, demonstrates anti-tumor activity in a phase 2 study of cytokine-refractory, metastatic renal cell cancer (RCC). J Clin Oncol. 2005;23(suppl 1):S380A;abstr 4509
  57. Wood JM, Bold G, Buchdunger E, et al. PTK787/ZK 222584, a novel and potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, impairs vascular endothelial growth factor-induced responses and tumor growth after oral administration. Cancer Res. 2000;60:2178–2189
  58. Hecht JR, Trarbach T, Jaegger E, et al. A randomized, double-blind, placebo-controlled, phase III study in patients (Pts) with metastatic adenocarcinoma of the colon or rectum receiving first-line chemotherapy with oxaliplatin/5-fluorouracil/leucovorin and PTK787/ZK 222584 or placebo (CONFIRM-1). J Clin Oncol. 2005;23(suppl 1):S1090A;abstr 3
  59. Drevs J, Medinger M, Mross K, et al: Phase I clinical evaluation of AZD2171, a highly potent VEGF receptor tyrosine kinase inhibitor, in patients with advanced tumors. J Clin Oncol 2005 Annual Meeting Proceedings Part I 23(16S), 2005 (June 1 Suppl) (abstr 3002)
  60. Thomas AL, Morgan B, Horsfield MA, et al. Phase I study of the safety, tolerability, pharmacokinetics, and pharmacodynamics of PTK787/ZK 222584 administered twice daily in patients with advanced cancer. J Clin Oncol. 2005;23:4162–4171
  61. Nguyen QD, Shah SM, Hafiz G, et al. CLEAR-AMD 1 Study Group A phase I trial of an IV-administered vascular endothelial growth factor trap for treatment in patients with choroidal neovascularization due to age-related macular degeneration. Ophthalmology. 2006;113:1522-1522
  62. Izzedine H, Rixe O, Brocheriou I, Deray G. Thrombotic microangiopathy and anti-VEGF agents. Nephrol Dial Transplant. 2007;22:1481–1482
  63. Gilbert RE, Kelly DJ, McKay T, et al. PDGF signal transduction inhibition ameliorates experimental mesangial proliferative glomerulonephritis. Kidney Int. 2001;59:1324–1332
  64. Howie JB, Helyer BJ. The immunology and pathology of NZB mice. Adv Immunol. 1968;9:215–266
  65. Foster MH. Relevance of systemic lupus erythematosus nephritis animal models to human disease. Semin Nephrol. 1999;19:12–24
  66. Lassila M, Jandeleit-Dahm K, Seah KK, et al. Imatinib attenuates diabetic nephropathy in apolipoprotein E-knockout mice. J Am Soc Nephrol. 2005;16:363–373
  67. Schellings MW, Baumann M, van Leeuwen RE, et al. Imatinib attenuates end-organ damage in hypertensive homozygous TGR(mRen2) rats. Hypertension. 2006;47:467–474
  68. Francois H, Placier S, Flamant M, et al. Prevention of renal vascular and glomerular fibrosis by epidermal growth factor receptor inhibition. FASEB J. 2004;18:926–928
  69. Sane DC, Anton L, Brosnihan KB. Angiogenic growth factors and hypertension. Angiogenesis. 2004;7:193–201
  70. McCance KL, Huether SE. Pathophysiology: The Biologic Basis for Disease in Adults and Children. (ed 4). St. Louis, MO: Mosby; 2002;
  71. Henry TD, Annex BH, McKendall GR, et al. VIVA Investigators: The VIVA trial: Vascular endothelial growth factor in Ischemia for Vascular Angiogenesis. Circulation. 2003;107:1359–1365
  72. Tang JR, Markham NE, Lin YJ, et al. Inhaled nitric oxide attenuates pulmonary hypertension and improves lung growth in infant rats after neonatal treatment with a VEGF receptor inhibitor. Am J Physiol Lung Cell Mol Physiol. 2004;287:L344–L351
  73. Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol. 2005;23:1011–1027
  74. Wickman G, Hallin M, Salansky KA, et al. Further characterization of the potent VEGF/PDGF receptor tyrosine kinase inhibitor AG-013736 in preclinical tumor models for its antiangiogenesis and antitumor activity. Proc Am Assoc Cancer Res. 2003;44:865A;(abstr 3780)
  75. Feliers D, Chen X, Akis N, Choudhury GG, Madaio M, Kasinath BS. VEGF regulation of endothelial nitric oxide synthase in glomerular endothelial cells. Kidney Int. 2005;68:1648–1659
  76. Safar ME, Levy BI, Struijker-Boudier H. Current perspectives on arterial stiffness and pulse pressure in hypertension and cardiovascular diseases. Circulation. 2003;107:2864–2869
  77. Stefanadis CI, Karrayannacos PE, Boudoulas HK, et al. Medial necrosis and acute alterations in aortic distensibility following removal of the vasa vasorum of canine ascending aorta. Cardiovasc Res. 1993;27:951–956
  78. Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350:2335–2342
  79. Kincaid-Smith P. The renal lesion of preeclampsia revisited. Am J Kidney Dis. 1991;17:144–148
  80. Levine RJ, Maynard SE, Qian C, et al. Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med. 2004;350:672–683
  81. Laurinavicius A, Hurwitz S, Rennke HG. Collapsing glomerulopathy in HIV and non-HIV patients: A clinicopathological and follow-up study. Kidney Int. 1999;56:2203–2213
  82. Mares JE, Worah S, Mathew SV: Increased rates of hypertension (HTN) among patients with advanced carcinoma treated by bevacizumab. 41st Annual Meeting of the American Society of Clinical Oncology (ASCO), 2005 (abstr 4087)
  83. Hara A, Wada T, Furuichi K, et al. Blockade of VEGF accelerates proteinuria, via decrease in nephrin expression in rat crescentic glomerulonephritis. Kidney Int. 2006;69:1986–1995
  84. Kelly DJ, Aaltonen P, Cox AJ, et al. Expression of the slit-diaphragm protein, nephrin, in experimental diabetic nephropathy: Differing effects of anti-proteinuric therapies. Nephrol Dial Transplant. 2002;17:1327–1332
  85. Kitayama H, Maeshima Y, Takazawa Y, et al. Regulation of angiogenic factors in angiotensin II infusion model in association with tubulointerstitial injuries. Am J Hypertens. 2006;19:718–727
  86. Sato Y, Sonoda H. The vasohibin family (A negative regulatory system of angiogenesis genetically programmed in endothelial cells). Arterioscler Thromb Vasc Biol. 2007;27:37–41
  87. Kabbinavar F, Hurwitz HI, Fehrenbacher L, et al. Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J Clin Oncol. 2003;21:60–65
  88. Kabbinavar FF, Hambleton J, Mass RD, Hurwitz HI, Bergsland E, Sarkar S. Combined analysis of efficacy: The addition of bevacizumab to fluorouracil/leucovorin improves survival for patients with metastatic colorectal cancer. J Clin Oncol. 2005;23:3706–3712

 Originally published online as doi:10.1053/j.ajkd.2007.04.025 on June 28, 2007.

PII: S0272-6386(07)00835-9

doi: 10.1053/j.ajkd.2007.04.025

American Journal of Kidney Diseases
Volume 50, Issue 2 , Pages 203-218 , August 2007

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