Nephrotoxicity of anti-angiogenesis drugs

Cover Page

Abstract


Neoangiogenesis is a basic factor for most physiological as well as pathological processes i.e. tumor metastases. The most important is vascular endothelium growth factor (VEGF) and its’ receptors (VEGFR1/2) in angiogenesis processes. Nowadays antiangiogenic agents (which inhibit VEGF like bevacizumab neither VEGFR2 like ramucirumab) are widely used in very different chemotherapeutic regimens in clinical oncology. The signalling pathway VEGF-VEGFR plays a crucial role in supporting of adequate kidney function. Appearance of antiangiogenic drugs led to adverse nephrotoxic effects: arterial hypertension, proteinuria, rarely – nephrotic syndrome, and kidney dysfunction. Various hystological variants of nephropathy are described, however, in most cases, signs of thrombotic microangiopathy of the renal vessels are noted. This literature review discusses mechanisms, clinical and morphological aspects of nephropathy associated with antiangiogenic drugs.


Full Text

Restricted Access

About the authors

Katerina S. Grechukhina

Lomonosov Moscow State University; Loginov Moscow Clinical Scientific Center

Author for correspondence.
Email: dr.grechukhina@gmail.com
ORCID iD: 0000-0002-0616-5477

Russian Federation, Moscow

аспирант каф. внутренних болезней, мл. науч. сотр. отд-ния химиотерапии, врач-онколог

Natalia V. Chebotareva

Sechenov First Moscow State Medical University (Sechenov University)

Email: dr.grechukhina@gmail.com
ORCID iD: 0000-0003-2128-8560

Russian Federation, Moscow

д.м.н. проф., каф. внутренних, профессиональных болезней и ревматологии

Tatyana N. Krasnova

Lomonosov Moscow State University

Email: dr.grechukhina@gmail.com
ORCID iD: 0000-0002-7647-3942

Russian Federation, Moscow

зав. каф. внутренних болезней

References

  1. Светозарский Н.Л., Артифексова А.А., Светозарский С.Н. Фактор роста эндотелия сосудов: биологические свойства и практическое значение (обзор литературы). Journal of Siberian Medical Sciences. 2019;4:4-11 [Svetozarskiy N, Artifeksova A, Svetozarskiy S. Vascular endothelial growth factor: biological features and practical significance (literature review). Journal of Siberian Medical Sciences. 2019;4:4-11 (In Russ.)].
  2. Eremina V, Jefferson J, Kowalewska J. VEGF inhibition and renal thrombotic microangiopathy. N Engl J Med. 2008;358(11):1129-36. doi: 10.1056/NEJMoa0707330
  3. Niu G, Chen X. Vascular Endothelial Growth Factor as an Anti-angiogenic Target for Cancer Therapy. Cur Drug Targets. 2010;11(8):1000-17. doi: 10.2174/138945010791591395
  4. Мещеряков А.А. Антиангиогенная терапия диссеминированного колоректального рака. Современная онкология. 2003;15(3):12-5 [Mesheryakov A. Antiangionenic therapy of disseminated colorectal cancer. Journal of Modern Oncology. 2003;15(3):12-5 (in Russ.)].
  5. Трякин А.А. Таргетная терапия колоректального рака, рака желудка и поджелудочной железы. Практическая онкология. 2010;11(3):143-50 [Tryakin A. Target therapy of colorectal, gastric and pancreatic cancers. Practical oncology. 2010;11(3):143-50 (In Russ.)].
  6. Giantonio B, Catalano P, Meropol N. Bevacizumab in Combination With Oxaliplatin, Fluorouracil, and Leucovorin (FOLFOX4) for Previously Treated Metastatic Colorectal Cancer: Results From the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol. 2007;20:1539-44. doi: 10.1200/JCO.2006.09.6305
  7. Pastorino A, Di Bartolomeo M, Maiello E, et al. Aflibercept Plus FOLFIRI in the Real-life Setting: Safety and Quality of Life Data From the Italian Patient Cohort of the Aflibercept Safety and Quality-of-Life Program Study. Clin Colorectal Cancer. 2018;17(3):e457-e470. doi: 10.1016/j.clcc.2018.03.002
  8. Tabernero J, Takayuki Y, Cohn A. Ramucirumab versus placebo in combination with second- line FOLFIRI in patients with metastatic colorectal carcinoma that progressed during or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine (RAISE): a randomised, double-blind, multicentre, phase 3 study. Lancet Oncol. 2015;16:e262. doi: 10.1016/S1470-2045(15)70127
  9. Toriu A, et al. Renal-Limited Thrombotic Microangiopathy due to Bevacizumab Therapy for Metastatic Colorectal Cancer: A Case Report. Case Rep Oncol. 2019;12:391-400. doi: 10.1159/00050071
  10. Maitland M, Bakris G, Black H, 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. doi: 10.1093/jnci/djq091
  11. Vaidya V, Ozer J, Frank D, et al. Kidney Injury Molecule-1 Outperforms Traditional Biomarkers of Kidney Injury in Multi-site Preclinical Biomarker Qualification Studies. Nat Biotechnol. 2010;28(5):478-85. doi: 10.1038/nbt.1623
  12. Arnold D, Fuchs C, Tabernero J, et al. Meta-analysis of individual patient safety data from six randomized, placebo-controlled trials with the antiangiogenic VEGFR2-binding monoclonal antibody ramucirumab. Ann Oncol. 2017;28:2932-42. doi: 10.1093/annonc/mdx514
  13. Qi W, Shen Z, Tang L. Risk of Hypertension in Cancer Patients Treated with Aflibercept: A Systematic Review and Meta-Analysis. Clin Drug Investig. 2014;34:231-40. doi: 10.1007/s40261-014-0174-5
  14. Feldman D, Baum M, Ginsberg M, et al. Phase I trial of bevacizumab plus escalated doses ofsunitinib in patients with metastatic renal cell carcinoma. J Clin Oncol. 2009;27:1432-9. doi: 10.1200/JCO.2008.19.0108
  15. Azad N, Posadas E, Kwitkowski V, et al. Combination targeted therapy with sorafenib and bevacizumab results in enhanced toxicity and antitumor activity. J Clin Oncol. 2008;26:3709-14. doi: 10.1200/JCO.2007.10.8332
  16. Wu S, Chen J, Kudelka A, et al. Incidence and risk of hypertension with sorafenib in patients with cancer: a systematic review and meta-analysis. Lancet Oncol. 2008;9:117-23. doi: 10.1016/j.eururo.2018.05.002
  17. Gupta S, Parsa V, Heilbrun L, et al. Safety and efficacy of molecularly targeted agents in patients with metastatic kidney cancer with renal dysfunction. Anticancer Drugs. 2011;22:794-800. doi: 10.1097/CAD.0b013e328346af0d
  18. Miura S, Fujino M, Matsuo Y, et al. 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. doi: 10.1291/hypres.28.147
  19. Dirix LY, Maes H, Sweldens C. Treatment of arterial hypertension (AHT) associated with angiogenesis inhibitors. Ann Oncol. 2007;18:1121-2. doi: 10.1093/annonc/mdm205
  20. 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;278:12605-8. doi: 10.1074/jbc.C300012200
  21. 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(5):707-16. doi: 10.1172/JCI17423
  22. Zhu X, Wu S, Dahut W, Parikh C. 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. doi: 10.1053/j.ajkd.2006.11.039
  23. Yang J, Haworth L, Sherry R, 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. doi: 10.1056/NEJMoa021491
  24. Patel T, Morgan J, Demetri G, 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. doi: 10.1093/jnci/djm311
  25. Miller K, Chap L, Holmes F, 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. doi: 10.1200/JCO.2005.05.098
  26. Мещеряков А.А. Лечение и профилактика побочных эффектов антиангиогенной терапии у больных метастатическим колоректальным раком. Рос. онкологический журн. 2017;22(3):164-8 [Mesheryakov A. Treatment and prophylaxis of adverse events of antiogenic therapy in patients with colorectal cancer. Russian oncological journal. 2017;22(3):164-8 (In Russ.)]. doi: 10.18821/1028-9984-2017-22-3-164-168
  27. Eremina V, Baelde H, Quaggin S. Role of the VEGF – a signaling pathway in the glomerulus: evidence for crosstalk between components of the glomerular filtration barrier. Nephron Physiology. 2007;106(2):32-7. doi: 10.1159/000101798
  28. Maynard S, Min J, Merchan J, et al. Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction hypertension, and proteinuria in preeclampsia. J Clin Invest. 2003;111(5):649-58. doi: 10.1172/JCI17189
  29. Abrahamson D. Glomerulogenesis in the developing kidney. Semin Nephrol. 1991;4(11):375-89.
  30. 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(5):707-16. doi: 10.1172/JCI17423
  31. Hara A, Wada T, Furuchi K, et al. Blockade of VEGF accelerates proteinuria via decrease in nephrin expression in rat crescentic glomerulonephritis. Kidney Int. 2006;69(11):1986-95. doi: 10.1038/sj.ki.5000439
  32. Hanna R, et al. Nephrotoxicity induced by intravitreal vascular endothelial growth factor inhibitors: emerging evidence. Kidney Int. 2019;96(3):572-80. doi: 10.1016/j.kint.2019.02.042
  33. Diabetic Retinopathy Clinical Research Network, et al. A phase II randomized clinical trial of intravitreal bevacizumab for diabetic macular edema. Ophthalmology. 2007;114(10):1860-7. doi: 10.1016/j.ophtha.2007.05.062
  34. Georgalas I, Papaconstantinou D, Papadopoulos K, et al. Renal Injury Following Intravitreal Anti-VEGF Administration in Diabetic Patients with Proliferative Diabetic Retinopathy and Chronic Kidney Disease – A Possible Side Effect? Cur Drug Safety. 2014;9:156. doi: 10.2174/1574886309666140211113635
  35. Khneizer P, Gebran T, Al-Taee M, et al. Self-limited membranous nephropathy after intravitreal bevacizumab therapy for age-related macular degeneration. J Nephropathol. 2017;6(3):134-7. doi: 10.15171/jnp.2017.23
  36. Morale E, Moliz C, Gutierrez E. Renal damage associated to intravitreal administration of ranibizumab. Nefrología (English Edition). 2017;37(6):653-5. doi: 10.1016/j.nefroe.2017.10.007
  37. Eremina V, Quaggin S. Biology of anti-angiogenic therapy-induced thrombotic microangiopathy. Semin Nephrol. 2010;30:582-90. doi: 10.1016/j.semnephrol.2010.09.006
  38. Horowitz J, 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. doi: 10.1161/01.atv.17.11.2793
  39. Bollee G, Patey N, Cazajous G, et al. Thrombotic microangiopathy secondary to VEGF pathway inhibition by sunitinib. Nephrol Dial Transplant. 2009;24:682-5. doi: 10.1093/ndt/gfn657
  40. Izzedine H, Brocheriou I, Deray G, Rixe O. Thrombotic microangiopathy and anti-VEGF agents. Nephrol Dial Transplant. 2007;22:1481-2. doi: 10.1093/ndt.gfl565
  41. Estrada C, Maldonado A, Mallipattu S. Therapeutic Inhibition of VEGF Signaling and Associated Nephrotoxicities. JASN. 2019;30(2):187-200. doi: 10.1681/ASN.2018080853
  42. Vicky B, Katarina M, David K. Thrombotic Microangiopathy and the kidney. Clin J Am Soc Nephrol. 2018;13(2):300–17. doi: 10.2215/CJN.00620117
  43. Shimamura Y, Maeda T, Takizawa H. Bevacizumab-induced thrombotic microangiopathy and nephrotic syndrome. Clin Exp Nephrol. 2019;23:142-3. doi: 10.1007/s10157-018-1596-9
  44. Fujii T, Kawaasoe K, Tonooka A, et al. Nephrotic syndrome associated with ramucirumab therapy. A single-center case series and literature review. Medicine (Baltimore). 2019;98(27):e16236. doi: 10.1097/MD.0000000000016236
  45. Izzedine H, Ederhy S, Goldwasser F, et al. Management of hypertension in angiogenesis inhibitor-treated patients. Ann Oncol. 2009;20:807-15. doi: 10.1093/annonc/mdn713
  46. Pfister F, Amann K, Daniel C, et al. Characteristic morphological changes in anti-VEGF therapy-induced glomerular microangiopathy. Histopathology. 2018;73(6):990-1001. doi: 10.1111/his.13716
  47. Yamada R, Okawa T, Matsuo K, et al. Renal-limited thrombotic microangiopathy after switching from bevacizumab to ramucirumab: a case report. BMC Nephrol. 2019;20(1):14. doi: 10.1186/s12882-018-1194-9
  48. Khurana A. Allergic interstitial nephritis possibly related to sunitinib use. Am J Geriatr Pharmacother. 2007;5:341-4. doi: 10.1186/s12882-018-1194-9
  49. Nasr S, Snyder R, Bhagat G, Markowitz G. Chronic lymphocytic leukemia and cryoglobulinemic glomerulonephritis. Kidney Int. 2007;71:93. doi: 10.1038/sj.ki.5001891
  50. Costero O, Picazo M, 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. doi: 10.1093/ndt/gfp666
  51. Pellé G, Shweke N, Duong Van Huyen J, et al. Systemic and Kidney Toxicity of Intraocular Administration of Vascular Endothelial Growth Factor Inhibitors. Am J Kidney Dis. 2011;579(5):756-9. doi: 10.1053/j.ajkd.2010.11.030
  52. Valdivia M, Mendoza M, Toro Prieto T, et al. Relapse of minimal change disease nephrotic syndrome after administering intravitreal bevacizumab. Nefrología (English Edition). 2014;34(3):373-424. doi: 10.3265/Nefrologia.pre2014.Mar.12388
  53. Hanna R, Lopez E, Wilson J, et al. Minimal change disease onset observed after bevacizumab administration. Clin Kidney J. 2016;9(2):239-44. doi: 10.1093/ckj/sfv139

Statistics

Views

Abstract - 45

PDF (Russian) - 7

Cited-By


PlumX

Dimensions

Refbacks

  • There are currently no refbacks.


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
 

Address of the Editorial Office:

  • Novij Zykovskij proezd, 3, 40, Moscow, 125167

Correspondence address:

  • Novoslobodskaya str 31c4., Moscow, 127005, Russian Federation

Managing Editor:

 

© 2018 "Consilium Medicum" Publishing house

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies