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Updated: May 20, 2026
Assessment of Kidney Function in Mouse Models of Glomerular Disease
Published on: June 30, 2018
Chronic VEGF blockade worsens glomerular injury in the remnant kidney model
Flavia G Machado1, Patrícia Semedo Kuriki, Clarice K Fujihara
1Laboratory of Renal Pathophysiology (LIM-16), Renal Division, Department of Clinical Medicine, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
Abstract:
VEGF inhibition can promote renal vascular and parenchymal injury, causing proteinuria, hypertension and thrombotic microangiopathy. The mechanisms underlying these side effects are unclear. We investigated the renal effects of the administration, during 45 days, of sunitinib (Su), a VEGF receptor inhibitor, to rats with 5/6 renal ablation (Nx). Adult male Munich-Wistar rats were distributed among groups S+V, sham-operated rats receiving vehicle only; S+Su, S rats given Su, 4 mg/kg/day; Nx+V, Nx rats receiving V; and Nx+Su, Nx rats receiving Su. Su caused no change in Group S. Seven and 45 days after renal ablation, renal cortical interstitium was expanded, in association with rarefaction of peritubular capillaries. Su did not worsen hypertension, proteinuria or interstitial expansion, nor did it affect capillary rarefaction, suggesting little angiogenic activity in this model. Nx animals exhibited glomerulosclerosis (GS), which was aggravated by Su. This effect could not be explained by podocyte damage, nor could it be ascribed to tuft hypertrophy or hyperplasia. GS may have derived from organization of capillary microthrombi, frequently observed in Group Nx+Su. Treatment with Su did not reduce the fractional glomerular endothelial area, suggesting functional rather than structural cell injury. Chronic VEGF inhibition has little effect on normal rats, but can affect glomerular endothelium when renal damage is already present.
Insights
Vascular Endothelial Growth Factor (VEGF) inhibition can cause kidney injury. In rats with renal ablation, sunitinib (VEGF receptor inhibitor) aggravated glomerulosclerosis, potentially via microthrombi, but did not worsen other renal injuries.
Area of Science:
- Nephrology
- Vascular Biology
- Pharmacology
Background:
- Vascular Endothelial Growth Factor (VEGF) inhibition is known to cause renal vascular and parenchymal injury, including proteinuria, hypertension, and thrombotic microangiopathy.
- The precise mechanisms behind these adverse renal effects remain incompletely understood.
Purpose of the Study:
- To investigate the renal effects of sunitinib, a VEGF receptor inhibitor, in a rat model of 5/6 renal ablation.
- To elucidate the impact of chronic VEGF inhibition on established renal damage.
Main Methods:
- Adult male Munich-Wistar rats underwent 5/6 renal ablation (Nx) or sham operation (S).
- Animals received either vehicle (V) or sunitinib (Su, 4 mg/kg/day) for 45 days.
- Renal tissues were analyzed for interstitial expansion, capillary rarefaction, glomerulosclerosis, podocyte damage, and glomerular endothelial area.
Main Results:
- Sunitinib administration did not alter renal parameters in sham-operated rats.
- In renally ablated rats, sunitinib aggravated glomerulosclerosis, which appeared to originate from organized capillary microthrombi.
- Sunitinib did not worsen hypertension, proteinuria, interstitial expansion, or capillary rarefaction in the renal ablation model.
Conclusions:
- Chronic VEGF inhibition has minimal impact on normal rat kidneys.
- In the context of pre-existing renal damage, VEGF inhibition with sunitinib can exacerbate glomerulosclerosis, possibly through the formation of glomerular microthrombi.
- The observed glomerular injury appears functional rather than structural, as indicated by unchanged fractional glomerular endothelial area.
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