Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med. 1971;285:1182–6.
PubMed
Article
CAS
Google Scholar
Eremina V, Quaggin SE. Biology of anti-angiogenic therapy-induced thrombotic microangiopathy. Semin Nephrol. 2010;30:582–90.
PubMed
Article
CAS
Google Scholar
Eskens FA, Verweij J. The clinical toxicity profile of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR) targeting angiogenesis inhibitors; a review. Eur J Cancer. 2006;42:3127–39.
PubMed
Article
CAS
Google Scholar
Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med. 2003;9:669–76.
PubMed
Article
CAS
Google Scholar
• Kappers MH, van Esch JH, Sleijfer S, Danser AH, van den Meiracker AH. Cardiovascular and renal toxicity during angiogenesis inhibition: clinical and mechanistic aspects. J Hypertens. 2009;27:2297–309. Excellent overview of the vascular effects and toxicities of anti-VEGF agents.
PubMed
Article
CAS
Google Scholar
Ebos JM, Bocci G, Man S, et al. A naturally occurring soluble form of vascular endothelial growth factor receptor 2 detected in mouse and human plasma. Mol Cancer Res. 2004;2:315–26.
PubMed
CAS
Google Scholar
Kitamoto Y, Tokunaga H, Miyamoto K, Tomita K. VEGF is an essential molecule for glomerular structuring. Nephrol Dial Transplant. 2002;17 Suppl 9:25–7.
PubMed
Article
CAS
Google Scholar
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;49:186–93.
PubMed
Article
CAS
Google Scholar
Sane DC, Anton L, Brosnihan KB. Angiogenic growth factors and hypertension. Angiogenesis. 2004;7:193–201.
PubMed
Article
CAS
Google Scholar
Verheul HM, Pinedo HM. Possible molecular mechanisms involved in the toxicity of angiogenesis inhibition. Nat Rev Cancer. 2007;7:475–85.
PubMed
Article
CAS
Google Scholar
Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350:2335–42.
PubMed
Article
CAS
Google Scholar
Miller KD, Chap LI, Holmes FA, et al. Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol. 2005;23:792–9.
PubMed
Article
CAS
Google Scholar
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;349:427–34.
PubMed
Article
CAS
Google Scholar
Mourad JJ, Levy BI. Mechanisms of antiangiogenic-induced arterial hypertension. Curr Hypertens Rep. 2011;13:289–93.
PubMed
Article
CAS
Google Scholar
Chen HX, Cleck JN. Adverse effects of anticancer agents that target the VEGF pathway. Nat Rev Clin Oncol. 2009;6:465–77.
PubMed
Article
CAS
Google Scholar
Drevs J, Siegert P, Medinger M, et al. Phase I clinical study of AZD2171, an oral vascular endothelial growth factor signaling inhibitor, in patients with advanced solid tumors. J Clin Oncol. 2007;25:3045–54.
PubMed
Article
CAS
Google Scholar
Sleijfer S, Ray-Coquard I, Papai Z, et al. Pazopanib, a multikinase angiogenesis inhibitor, in patients with relapsed or refractory advanced soft tissue sarcoma: a phase II study from the European organisation for research and treatment of cancer-soft tissue and bone sarcoma group (EORTC study 62043). J Clin Oncol. 2009;27:3126–32.
PubMed
Article
CAS
Google Scholar
Trotti A, Byhardt R, Stetz JA, et al. Common toxicity criteria: version 2.0. An improved reference for grading the acute effects of cancer treatment: impact on radiotherapy. Int J Radiat Oncol Biol Phys. 2000;47:13–47.
PubMed
Article
CAS
Google Scholar
Agabiti-Rosei E. Structural and functional changes of the microcirculation in hypertension: influence of pharmacological therapy. Drugs. 2003;63(Spec No 1):19–29.
PubMed
Article
CAS
Google Scholar
Trotti A, Colevas AD, Setser A, et al. CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol. 2003;13:176–81.
PubMed
Article
Google Scholar
Chobanian AV, Bakris GL, Black HR, et al. Seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure. Hypertension. 2003;42:1206–52.
PubMed
Article
CAS
Google Scholar
Wu S, Chen JJ, 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. 2008;9:117–23.
PubMed
Article
CAS
Google Scholar
Feldman DR, Baum MS, Ginsberg MS, et al. Phase I trial of bevacizumab plus escalated doses of sunitinib in patients with metastatic renal cell carcinoma. J Clin Oncol. 2009;27:1432–9.
PubMed
Article
CAS
Google Scholar
Azad NS, Posadas EM, Kwitkowski VE, et al. Combination targeted therapy with sorafenib and bevacizumab results in enhanced toxicity and antitumor activity. J Clin Oncol. 2008;26:3709–14.
PubMed
Article
CAS
Google Scholar
Maitland ML, Bakris GL, Black HR, et al. Initial assessment, surveillance, and management of blood pressure in patients receiving vascular endothelial growth factor signaling pathway inhibitors. J Natl Cancer Inst. 2010;102:596–604.
PubMed
Article
CAS
Google Scholar
Hood JD, Meininger CJ, Ziche M, Granger HJ. VEGF upregulates ecNOS message, protein, and NO production in human endothelial cells. Am J Physiol. 1998;274:H1054–8.
PubMed
CAS
Google Scholar
Horowitz JR, Rivard A, van der Zee R, et al. Vascular endothelial growth factor/vascular permeability factor produces nitric oxide-dependent hypotension. Evidence for a maintenance role in quiescent adult endothelium. Arterioscler Thromb Vasc Biol. 1997;17:2793–800.
PubMed
Article
CAS
Google Scholar
Zachary I. VEGF signalling: integration and multi-tasking in endothelial cell biology. Biochem Soc Trans. 2003;31:1171–7.
PubMed
Article
CAS
Google Scholar
Gelinas DS, Bernatchez PN, Rollin S, Bazan NG, Sirois MG. Immediate and delayed VEGF-mediated NO synthesis in endothelial cells: role of PI3K, PKC and PLC pathways. Br J Pharmacol. 2002;137:1021–30.
PubMed
Article
CAS
Google Scholar
Li B, Ogasawara AK, Yang R, et al. KDR (VEGF receptor 2) is the major mediator for the hypotensive effect of VEGF. Hypertension. 2002;39:1095–100.
PubMed
Article
CAS
Google Scholar
Henry TD, Annex BH, McKendall GR, et al. The VIVA trial: vascular endothelial growth factor in ischemia for vascular angiogenesis. Circulation. 2003;107:1359–65.
PubMed
Article
CAS
Google Scholar
Zou AP, Cowley Jr AW. Role of nitric oxide in the control of renal function and salt sensitivity. Curr Hypertens Rep. 1999;1:178–86.
PubMed
Article
CAS
Google Scholar
Mourad JJ, des Guetz G, Debbabi H, Levy BI. Blood pressure rise following angiogenesis inhibition by bevacizumab. A crucial role for microcirculation. Ann Oncol. 2008;19:927–34.
PubMed
Article
Google Scholar
Feihl F, Liaudet L, Waeber B, Levy BI. Hypertension: a disease of the microcirculation? Hypertension. 2006;48:1012–7.
PubMed
Article
CAS
Google Scholar
Kiefer FN, Misteli H, Kalak N, et al. Inhibition of NO biosynthesis, but not elevated blood pressure, reduces angiogenesis in rat models of secondary hypertension. Blood Press. 2002;11:116–24.
PubMed
Article
CAS
Google Scholar
Steeghs N, Gelderblom H, Roodt JO, et al. Hypertension and rarefaction during treatment with telatinib, a small molecule angiogenesis inhibitor. Clin Cancer Res. 2008;14:3470–6.
PubMed
Article
CAS
Google Scholar
Veronese ML, Mosenkis A, Flaherty KT, et al. Mechanisms of hypertension associated with BAY 43–9006. J Clin Oncol. 2006;24:1363–9.
PubMed
Article
CAS
Google Scholar
Mundel P, Kriz W. Cell culture of podocytes. Exp Nephrol. 1996;4:263–6.
PubMed
CAS
Google Scholar
Nagata M, Yamaguchi Y, Ito K. Loss of mitotic activity and the expression of vimentin in glomerular epithelial cells of developing human kidneys. Anat Embryol (Berl). 1993;187:275–9.
Article
CAS
Google Scholar
Reiser J, Kriz W, Kretzler M, Mundel P. The glomerular slit diaphragm is a modified adherens junction. J Am Soc Nephrol. 2000;11:1–8.
PubMed
CAS
Google Scholar
Kestila M, Lenkkeri U, Mannikko M, et al. Positionally cloned gene for a novel glomerular protein—nephrin—is mutated in congenital nephrotic syndrome. Mol Cell. 1998;1:575–82.
PubMed
Article
CAS
Google Scholar
Donoviel DB, Freed DD, Vogel H, et al. Proteinuria and perinatal lethality in mice lacking NEPH1, a novel protein with homology to NEPHRIN. Mol Cell Biol. 2001;21:4829–36.
PubMed
Article
CAS
Google Scholar
Schwarz K, Simons M, Reiser J, et al. Podocin, a raft-associated component of the glomerular slit diaphragm, interacts with CD2AP and nephrin. J Clin Invest. 2001;108:1621–9.
PubMed
CAS
Google Scholar
Shih NY, Li J, Karpitskii V, et al. Congenital nephrotic syndrome in mice lacking CD2-associated protein. Science. 1999;286:312–5.
PubMed
Article
CAS
Google Scholar
Barisoni L, Kriz W, Mundel P, D’Agati V. The dysregulated podocyte phenotype: a novel concept in the pathogenesis of collapsing idiopathic focal segmental glomerulosclerosis and HIV-associated nephropathy. J Am Soc Nephrol. 1999;10:51–61.
PubMed
CAS
Google Scholar
Garovic VD, Wagner SJ, Petrovic LM, et al. Glomerular expression of nephrin and synaptopodin, but not podocin, is decreased in kidney sections from women with preeclampsia. Nephrol Dial Transplant. 2007;22:1136–43.
PubMed
Article
CAS
Google Scholar
Eremina V, Jefferson JA, Kowalewska J, et al. VEGF inhibition and renal thrombotic microangiopathy. N Engl J Med. 2008;358:1129–36.
PubMed
Article
CAS
Google Scholar
Patel TV, Morgan JA, Demetri GD, 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. 2008;100:282–4.
PubMed
Article
CAS
Google Scholar
Eskens FAP, van Doorn A. An open label phase I dose escalation study of KRN951, a tyrosine kinase inhibitor of vascular endothelial growth factor receptor 2 and 1 in a 4 week on, 2 week off schedule in patients with advanced solid tumors (Abstract). J Clin Oncol. 2006;24:2034.
Google Scholar
Izzedine H, Massard C, Spano JP, et al. VEGF signalling inhibition-induced proteinuria: Mechanisms, significance and management. Eur J Cancer. 2010;46:439–48.
PubMed
Article
CAS
Google Scholar
Nasr SH, Snyder RW, Bhagat G, Markowitz GS. Chronic lymphocytic leukemia and cryoglobulinemic glomerulonephritis. Kidney Int. 2007;71:93.
PubMed
Article
CAS
Google Scholar
Khurana A. Allergic interstitial nephritis possibly related to sunitinib use. Am J Geriatr Pharmacother. 2007;5:341–4.
PubMed
Article
CAS
Google Scholar
Izzedine H, Brocheriou I, Rixe O, Deray G. Interstitial nephritis in a patient taking sorafenib. Nephrol Dial Transplant. 2007;22:2411.
PubMed
Article
Google Scholar
Stokes MB, Erazo MC, D’Agati VD. Glomerular disease related to anti-VEGF therapy. Kidney Int. 2008;74:1487–91.
PubMed
Article
CAS
Google Scholar
Stylianou K, Lioudaki E, Papadimitraki E, et al. Crescentic glomerulonephritis associated with vascular endothelial growth factor (VEGF) inhibitor and bisphosphonate administration. Nephrol Dial Transplant. 2011;26:1742–5.
PubMed
Article
CAS
Google Scholar
Costero O, Picazo ML, Zamora P, et al. Inhibition of tyrosine kinases by sunitinib associated with focal segmental glomerulosclerosis lesion in addition to thrombotic microangiopathy. Nephrol Dial Transplant. 2010;25:1001–3.
PubMed
Article
CAS
Google Scholar
Bollee G, Patey N, Cazajous G, et al. Thrombotic microangiopathy secondary to VEGF pathway inhibition by sunitinib. Nephrol Dial Transplant. 2009;24:682–5.
PubMed
Article
CAS
Google Scholar
Izzedine H, Brocheriou I, Deray G, Rixe O. Thrombotic microangiopathy and anti-VEGF agents. Nephrol Dial Transplant. 2007;22:1481–2.
PubMed
Article
Google Scholar
Pelle G, Shweke N, Duong Van Huyen JP, et al. Systemic and kidney toxicity of intraocular administration of vascular endothelial growth factor inhibitors. Am J Kidney Dis. 2011;57:756–9.
PubMed
Article
CAS
Google Scholar
Yu D, Petermann A, Kunter U, et al. Urinary podocyte loss is a more specific marker of ongoing glomerular damage than proteinuria. J Am Soc Nephrol. 2005;16:1733–41.
PubMed
Article
CAS
Google Scholar
•• Müller-Deile J, Bröcker V, Grünwald V, et al. Renal side effects of VEGF-blocking therapy. NDT Plus. 2010;3:172–5. First article reporting the presence of podocyturia in patients with proteinuria treated with anti-VEGF therapy.
Article
Google Scholar
Takahashi D, Nagahama K, Tsuura Y, Tanaka H, Tamura T. Sunitinib-induced nephrotic syndrome and irreversible renal dysfunction. Clin Exp Nephrol. 2011.
•• Steeghs N, Rabelink TJ, op ‘t Roodt J, et al. Reversibility of capillary density after discontinuation of bevacizumab treatment. Ann Oncol. 2010;21:1100–5. First study showing that decreased capillary density as a result of bevacizumab is reversible and that capillary density may represent a marker of treatment efficacy.
PubMed
Article
CAS
Google Scholar
Ravaud A, Sire M. Arterial hypertension and clinical benefit of sunitinib, sorafenib and bevacizumab in first and second-line treatment of metastatic renal cell cancer. Ann Oncol. 2009;20:966–7. author reply 7.
PubMed
Article
CAS
Google Scholar
Rixe O, Billemont B, Izzedine H. Hypertension as a predictive factor of Sunitinib activity. Ann Oncol. 2007;18:1117.
PubMed
Article
CAS
Google Scholar
Levy BI. Blood pressure as a potential biomarker of the efficacy angiogenesis inhibitor. Ann Oncol. 2009;20:200–3.
PubMed
Article
CAS
Google Scholar
Bono P, Elfving H, Utriainen T, et al. Hypertension and clinical benefit of bevacizumab in the treatment of advanced renal cell carcinoma. Ann Oncol. 2009;20:393–4.
PubMed
Article
CAS
Google Scholar
Mir O, Ropert S, Alexandre J, Goldwasser F. Hypertension as a surrogate marker for the activity of anti-VEGF agents. Ann Oncol. 2009;20:967–70.
PubMed
Article
CAS
Google Scholar
• Osterlund P, Soveri LM, Isoniemi H, et al. Hypertension and overall survival in metastatic colorectal cancer patients treated with bevacizumab-containing chemotherapy. Br J Cancer. 2011;104:599–604. Study that most clearly demonstrates an association between hypertension and overall survival in patients treated with bevacizumab.
PubMed
Article
CAS
Google Scholar
Kim JJ, Vaziri SAJ, Rini BI, et al. Association of VEGF and VEGFR2 single nucleotide polymorphisms with hypertension and clinical outcome in metastatic clear cell renal cell carcinoma patients treated with sunitinib. Cancer. 2012:118(7):1946–54.
Google Scholar
Garcia-Donas J, Esteban E, Leandro-Garcia LJ, et al. Single nucleotide polymorphism associations with response and toxic effects in patients with advanced renal-cell carcinoma treated with first-line sunitinib: a multicentre, observational, prospective study. Lancet Oncol. 2011;12:1143–50.
PubMed
Article
CAS
Google Scholar
Langenberg MH, van Herpen CM, De Bono J, et al. Effective strategies for management of hypertension after vascular endothelial growth factor signaling inhibition therapy: results from a phase II randomized, factorial, double-blind study of Cediranib in patients with advanced solid tumors. J Clin Oncol. 2009;27:6152–9.
PubMed
Article
CAS
Google Scholar
Miura S, Fujino M, Matsuo Y, Tanigawa H, Saku K. Nifedipine-induced vascular endothelial growth factor secretion from coronary smooth muscle cells promotes endothelial tube formation via the kinase insert domain-containing receptor/fetal liver kinase-1/NO pathway. Hypertens Res. 2005;28:147–53.
PubMed
Article
CAS
Google Scholar
Molteni A, Heffelfinger S, Moulder JE, Uhal B, Castellani WJ. Potential deployment of angiotensin I converting enzyme inhibitors and of angiotensin II type 1 and type 2 receptor blockers in cancer chemotherapy. Anticancer Agents Med Chem. 2006;6:451–60.
PubMed
Article
CAS
Google Scholar
Izzedine H, Ederhy S, Goldwasser F, et al. Management of hypertension in angiogenesis inhibitor-treated patients. Ann Oncol. 2009;20:807–15.
PubMed
Article
CAS
Google Scholar
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;17:1327–32.
PubMed
Article
CAS
Google Scholar
Dirix LY, Maes H, Sweldens C. Treatment of arterial hypertension (AHT) associated with angiogenesis inhibitors. Ann Oncol. 2007;18:1121–2.
PubMed
Article
CAS
Google Scholar
Oliver JJ, Melville VP, Webb DJ. Effect of regular phosphodiesterase type 5 inhibition in hypertension. Hypertension. 2006;48:622–7.
PubMed
Article
CAS
Google Scholar
Porta C, Paglino C, Imarisio I, Bonomi L. Uncovering Pandora’s vase: the growing problem of new toxicities from novel anticancer agents. The case of sorafenib and sunitinib. Clin Exp Med. 2007;7:127–34.
PubMed
Article
CAS
Google Scholar
Launay-Vacher V, Ayllon J, Janus N, et al. Evolution of renal function in patients treated with antiangiogenics after nephrectomy for renal cell carcinoma. Urol Oncol. 2011;29:492–4.
PubMed
Article
CAS
Google Scholar
Gupta S, Parsa V, Heilbrun LK, et al. Safety and efficacy of molecularly targeted agents in patients with metastatic kidney cancer with renal dysfunction. Anticancer Drugs. 2011;22:794–800.
PubMed
Article
CAS
Google Scholar
Raina S, Honer M, Kramer SD, et al. Anti-VEGF antibody treatment accelerates polycystic kidney disease. Am J Physiol Renal Physiol. 2011;301:F773–83.
PubMed
Article
CAS
Google Scholar