Nephrotoxicity induced by vascular endothelial growth factor inhibitors

Vascular endothelial growth factor (VEGF) is a special mitogen for vascular endothelial cells, an essential endogenous angiogenic cytokine, and the principal controller of vascular growth that plays a fundamental role in therapeutic angiogenesis pathways. VEGF-targeted therapy is categorized into the group of angiogenesis inhibitors that inhibit the expression or the activity of VEGF. It comprises counteracting VEGF antibodies, VEGF receptors, VEGF-trap, and tyrosine kinase inhibitor (TKIs) with selectivity for VEGF receptors. The kidney is both a target and a source of VEGF. VEGF may be a vital mediator to restore some types of renal diseases (e.g., non-diabetic renal diseases) and harmful in some other diseases (e.g., diabetes and diabetes complications). Due to their ability to prevent angiogenesis, VEGF inhibitors have been found as a powerful tool to treat angiogenesis-dependent diseases, including cancer and diabetic retinopathy. VEGF preserves the renal structure and function in normal physiologic conditions. Therefore, all treatments that inhibit the VEGF pathway may lead to renal disorders, especially renovascular diseases such as hypertension, proteinuria, nephrotic syndrome, decreased glomerular filtration rate (GFR), and thrombotic microangiopathy (TMA). In the present study, we reviewed some related reports and associated mechanisms, especially for hypertension and proteinuria.

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Expression of vascular endothelial growth factor (VEGF) receptors in rat corpus luteum: regulation by oestradiol during mid-pregnancy

Reproduction ◽

10.1530/rep.0.1220875 ◽

2001 ◽

pp. 875-881 ◽

Cited By ~ 17

Author(s):

N Sugino ◽

S Kashida ◽

S Takiguchi ◽

A Karube-Harada ◽

H Kato

Keyword(s):

Vascular Endothelial Growth Factor ◽

Endothelial Cells ◽

Growth Factor ◽

Corpus Luteum ◽

Vascular Endothelial Cells ◽

Corpora Lutea ◽

Vascular Endothelial ◽

Vegf Receptors ◽

Luteal Cells ◽

Endothelial Growth Factor

The aim of this study was to investigate the expression of vascular endothelial growth factor (VEGF) receptors, the fms-like tyrosine kinase (flt-1) and kinase insert domain-containing region (KDR), in corpora lutea obtained at different stages of the oestrous cycle and during pregnancy in rats. Immunohistochemistry revealed that both flt-1 and KDR were localized in luteal cells in addition to vascular endothelial cells, and that the intensity of staining was stronger in pregnant rats than in cyclic rats. Rats undergoing hypophysectomy-hysterectomy on day 12 of pregnancy were treated with oestradiol until day 15 of pregnancy to determine whether oestradiol is involved in expression of flt-1 and KDR mRNA in the corpus luteum during mid-pregnancy. The flt-1 and KDR mRNA contents in the corpus luteum were decreased significantly by hypophysectomy-hysterectomy, and these decreases recovered significantly after oestradiol treatment. Changes in the mass of the corpus luteum and serum progesterone concentrations paralleled the changes in expression of flt-1 and KDR mRNA. Developmental studies indicated that flt-1 and KDR mRNA contents in the corpus luteum were constant until day 15 of pregnancy but decreased significantly on day 21 of pregnancy. In conclusion, both flt-1 and KDR were expressed in luteal cells in addition to vascular endothelial cells, and expression was upregulated by oestradiol during mid-pregnancy. flt-1 and KDR may play a role in development of the corpus luteum and in production of progesterone during mid-pregnancy in rats.

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Vascular endothelial growth factor-mediated peritoneal neoangiogenesis in peritoneal dialysis

Peritoneal Dialysis International ◽

10.1177/08968608211004683 ◽

2021 ◽

pp. 089686082110046

Author(s):

Yingfeng Shi ◽

Yan Hu ◽

Binbin Cui ◽

Shougang Zhuang ◽

Na Liu

Keyword(s):

Vascular Endothelial Growth Factor ◽

Peritoneal Dialysis ◽

Growth Factor ◽

Vascular Endothelial Cells ◽

Renal Diseases ◽

Vascular Endothelial ◽

Ultrafiltration Failure ◽

Tumour Growth Factor ◽

End Stage ◽

Endothelial Growth Factor

Peritoneal dialysis (PD) is an important renal replacement therapy for patients with end-stage renal diseases, which is limited by peritoneal neoangiogenesis leading to ultrafiltration failure (UFF). Vascular endothelial growth factor (VEGF) and its receptors are key angiogenic factors involved in almost every step of peritoneal neoangiogenesis. Impaired mesothelial cells are the major sources of VEGF in the peritoneum. The expression of VEGF will be up-regulated in specific pathological conditions in PD patients, such as with non-biocompatible peritoneal dialysate, uremia and inflammation, and so on. Other working cells (i.e. vascular endothelial cells, macrophages and adipocytes) can also stimulate the secretion of VEGF. Meanwhile, hypoxia and activation of complement system further aggravate peritoneal injury and contribute to neoangiogenesis. There are several signalling pathways participating in VEGF-mediated peritoneal neoangiogenesis including tumour growth factor-β, Wnt/β-catenin, Notch and interleukin-6/signal transducer and activator of transcription 3. Moreover, VEGF is highly expressed in dialysate effluent of long-term PD patients and is associated with peritoneal transport function, which supports its role in the alteration of peritoneal structure and function. In this review, we systematically summarize the angiogenic effect of VEGF and evaluate it as a potential target for the prevention of peritoneal neoangiogenesis and UFF. Preservation of the peritoneal membrane using targeted therapy of VEGF-mediated peritoneal neoangiogenesis may increase the longevity of the PD modality for those who require life-long dialysis.

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