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Updated: Nov 2, 2025
Assessment of Kidney Function in Mouse Models of Glomerular Disease
Published on: June 30, 2018
VEGF-VEGFR2 inhibitor-associated hyaline occlusive glomerular microangiopathy: a Japanese single-center experience
Masatoyo Ozawa1, Hiroshi Ohtani2, Atsushi Komatsuda1
1Department of Hematology, Nephrology, and Rheumatology, Akita University Graduate School of Medicine, Akita, Japan.
Background:
Inhibitors of vascular endothelial growth factor (VEGF)-VEGF receptor 2 (VEGFR2) signaling, such as bevacizumab (Bmab), are used for the treatment of various advanced cancers. However, these inhibitors induce renal thrombotic microangiopathy (TMA). Recently, two European cohort studies showed a distinctive histopathological pseudothrombotic pattern different from TMA in Bmab-treated patients.
Methods:
We analyzed 9 renal biopsies from proteinuric cancer patients treated with VEGF-VEGFR2 inhibitors in our Japanese cohort. Clinical and laboratory features were also assessed in these patients.
Results:
All 9 patients had moderate to heavy proteinuria with normal or slightly elevated serum creatinine levels. On light microscopy, a patchy pattern of hemispherical/spherical lesions along glomerular capillary walls was a characteristic finding. On immunofluorescence microscopy, staining for immunoglobulins (IgM dominant) at varying intensities was observed mainly along glomerular capillary walls. Especially, hemispherical/spherical positive staining for immunoglobulins was a characteristic pattern. Immunohistochemical studies showed positive staining for immunoglobulins and negative staining for CD61-positive platelets in capillary hemispherical/spherical lesions and positive VEGF staining in podocytes. On electron microscopy, variably electron-dense material in dilated glomerular capillaries and partial effacement of podocyte foot processes were observed. After the withdrawal of VEGF-VEGFR2 inhibitors, proteinuria improved without any specific treatment in 8 patients.
Conclusions:
Histopathological findings in our patients treated with VEGF-VEGFR2 inhibitors were consistent with those observed in the recently described new form of Bmab-associated hyaline occlusive glomerular microangiopathy. This form should be considered in proteinuric cancer patients treated with VEGF-VEGFR2 inhibitors. Discontinuing VEGF-VEGFR2 inhibitors may lead to improvement of glomerular microangiopathy induced by these drugs.
Insights
VEGF-VEGFR2 inhibitors can cause kidney damage, presenting as a unique glomerular microangiopathy. Discontinuing these cancer treatments may improve kidney function and proteinuria in affected patients.
Area of Science:
- Nephrology
- Oncology
- Pathology
Background:
- Vascular endothelial growth factor (VEGF)-VEGF receptor 2 (VEGFR2) inhibitors are used in advanced cancer treatment.
- These inhibitors can cause renal thrombotic microangiopathy (TMA).
- A distinct pseudothrombotic pattern, different from TMA, has been observed in patients treated with bevacizumab (Bmab).
Purpose of the Study:
- To analyze renal biopsies and clinical features of proteinuric cancer patients treated with VEGF-VEGFR2 inhibitors.
- To characterize the histopathological findings in these patients.
- To compare findings with previously described Bmab-associated glomerular microangiopathy.
Main Methods:
- Analysis of 9 renal biopsies from proteinuric cancer patients treated with VEGF-VEGFR2 inhibitors.
- Assessment of clinical and laboratory features.
- Histopathological examination using light microscopy, immunofluorescence, immunohistochemistry, and electron microscopy.
Main Results:
- All patients presented with moderate to heavy proteinuria and normal/slightly elevated creatinine.
- Characteristic findings included hemispherical/spherical lesions along glomerular capillary walls with IgM deposition.
- Electron microscopy revealed electron-dense material in dilated capillaries and podocyte foot process effacement.
- Proteinuria improved in 8 out of 9 patients after discontinuing VEGF-VEGFR2 inhibitors.
Conclusions:
- Histopathological findings are consistent with a new form of Bmab-associated hyaline occlusive glomerular microangiopathy.
- This condition should be considered in proteinuric cancer patients receiving VEGF-VEGFR2 inhibitors.
- Discontinuation of VEGF-VEGFR2 inhibitors may improve drug-induced glomerular microangiopathy.
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