VEGF modulation and renal effects: Case report and review of the literature
Angiogenesis has been known for decades to be an essential step in cancer growth. In
recent years, the vascular endothelial growth factor (VEGF) family was identified as a crucial
stimulus (and product by tumors) for neovascularization, nutrition, oxygen delivery, and
metastatic dissemination; VEGF inhibition currently has an important role in cancer therapy.
The development and increased use of VEGF inhibitors has led to the identification of side
effects and renal complications. Vascular endothelial growth factor is produced by renal
podocytes to maintain a healthy endothelium, mesangium, and tubular structures. With the
disruption of nutritional processes in the kidney, there can be renal injury starting at the cellular
level and referred to by some experts as anti-VEGF nephropathy (hypertension, thrombotic
microangiopathy, proteinuria, renal failure).
Here we present the case of a man with renal cell carcinoma who was treated with surgical
resection and later started on sunitinib. He developed several acute and chronic medical
problems, including some related to anti-VEGF toxicity.
Hicklin DJ, Ellis LM. Role of the vascular endothelial
growth factor pathway in tumor growth and angiogenesis.
J Clin Oncol 2005;23(5):1011–1027.
Eremina V, Jefferson JA, Kowalewska J, et al. VEGF inhibition
and renal thrombotic microangiopathy. N Engl J Med
Skorecki K, Chertow GM, Marsden PA, et al. Brenner and
Rector’s The Kidney. Vol 10th: ELSEVIER; 2016.
Gurevich F, Perazella MA. Renal effects of anti-angiogenesis
therapy: update for the internist. Am J Med 2009;
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(2):186–193.
Robinson ES, Matulonis UA, Ivy P, et al. Rapid development
of hypertension and proteinuria with cediranib, an oral vascular
endothelial growth factor receptor inhibitor. Clin J Am
Soc Nephrol 2010;5(3):477–483.
Lovell AR, Ernst ME. Drug-induced hypertension: focus on
mechanisms and management. Curr Hypertens Rep 2017;
Kappers MH, van Esch JH, Sluiter W, et al. Hypertension
induced by the tyrosine kinase inhibitor sunitinib is associated
with increased circulating endothelin-1 levels. Hypertension
Small HY, Montezano AC, Rios FJ, et al. Hypertension due
to antiangiogenic cancer therapy with vascular endothelial
growth factor inhibitors: understanding and managing a new
syndrome. Can J Cardiol 2014;30(5):534–543.
Abernethy DR, Schwartz JB. Calcium-antagonist drugs.
N Engl J Med 1999;341(19):1447–1457.
Bollée G, Patey N, Cazajous G, et al. Thrombotic microangiopathy
secondary to VEGF pathway inhibition by sunitinib.
Nephrol Dial Transplant 2009;24(2):682–685.
Humphreys BD, Sharman JP, Henderson JM, et al. Gemcitabine-
associated thrombotic microangiopathy. Cancer. 2004;
Izzedine H, Sène D, Hadoux J, et al. Thrombotic microangiopathy
related to anti-VEGF agents: intensive versus conservative
treatment? Ann Oncol 2011;22(2):487–490.
Izzedine H, Brocheriou I, Deray G, et al. Thrombotic microangiopathy
and anti-VEGF agents. Nephrol Dial Transplant
Cavalieri S, Cosmai L, Genderini A, et al. Lenvatinib-induced
renal failure: two first-time case reports and review of literature.
Expert Opin Drug Metab Toxicol 2018;14(4):379–385.
Perico L, Mandalà M, Schieppati A, et al. BRAF signaling
pathway inhibition, podocyte injury, and nephrotic syndrome.
Am J Kidney Dis 2017;70(1):145–150.
Massey J. Posterior reversible encephalopathy syndrome
(PRES) with sub-arachnoid haemorrhage after bevacizumab
and 5-FU. J Clin Neurosci 2017;40:57–59.
Eryılmaz MK, Mutlu H, Salim DK, et al. Fatal posterior revesible
leukoencephalopathy syndrome associated coma induced
by bevacizumab in metastatic colorectal cancer and review
of literature. J Oncol Pharm Pract 2016;22(6):806–810.
Miaris N, Maltezou M, Papaxoinis G, et al. Posterior reversible
encephalopathy syndrome with concurrent nephrotic
syndrome in a patient treated with pazopanib for metastatic
renal cell carcinoma: case report and review of the literature.
Clin Genitourin Cancer 2017;15(1):e99–e103.
Yılmaz S, Özçakar ZB, Taktak A, et al. Anti-VEGF-related
thrombotic microangiopathy in a child presenting with
nephrotic syndrome. Pediatr Nephrol 2016;31(6):1029–1032.
Wang W, Cheng J, Mallon C, et al. Symptomatic secondary
polycythemia induced by anti-vegf therapy for the treatment
of metastatic renal cell carcinoma: a case series and review.
Clin Genitourin Cancer 2015;13(6):e391–395.
Cheungpasitporn W, Chebib FT, Cornell LD, et al. Intravitreal
antivascular endothelial growth factor therapy may
induce proteinuria and antibody mediated injury in renal
allografts. Transplantation 2015;99(11):2382–2386.
Haruhara K, Tsuboi N, Nakao M, et al. [A case of glomerulopathy
associated with the vascular endothelial growth
factor inhibitor bevacizumab]. Nihon Jinzo Gakkai Shi.
Usui J, Glezerman IG, Salvatore SP, et al. Clinicopathological
spectrum of kidney diseases in cancer patients treated
with vascular endothelial growth factor inhibitors: a report
of 5 cases and review of literature. Hum Pathol. 2014;45(9):
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? Curr
Drug Saf 2014;9(2):156–158.
Pakosch D, Papadimas D, Munding J, et al. Osteonecrosis
of the mandible due to anti-angiogenic agent, bevacizumab.
Oral Maxillofac Surg 2013;17(4):303–306.
- There are currently no refbacks.