Chronic VEGF Blockade Worsens Glomerular Injury in the Remnant Kidney Model

Autor(es)

Machado, Flavia G. ^[1] ; Kuriki, Patricia Semedo ^[2] ; Fujihara, Clarice K. ^[1] ; Fanelli, Camilla ^[1] ; Arias, Simone C. A. ^[1] ; Malheiros, Denise M. A. C. ^[1] ; Camara, Niels O. S. ^[2] ; Zatz, Roberto ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med, Dept Clin Med, Div Renal, Lab Renal Pathophysiol LIM 16, Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Fac Med, Immunol Lab, Div Nephrol, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 7, n. 6 JUN 22 2012.
• Citações Web of Science: 15

Resumo

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. (AU)

• Processo FAPESP: 11/10943-4 - Efeito da administração de um agente anti-angiogênico, malato de sunitinib (Sutent), no modelo de ablação renal de 5/6 (Nx)
• Beneficiário: Clarice Kazue Fujihara
• Modalidade de apoio: Auxílio à Pesquisa - Regular