All anti-vascular endothelial growth factor drugs can induce 'pre-eclampsia-like syndrome': a RARe study

Background. Specific therapies that target vascular endothelial growth factor (VEGF) and its receptors have improved the survival of patients with metastatic cancers, but can induce side effects. Renal side effects (proteinuria, hypertension and renal failure) are underestimated. Methods. The French RARe (Reins sous traitement Anti-VEGF Registre) study collects data on patients with cancer who had a renal biopsy because of major renal side effects during treatment with anti-VEGF drugs. Results. We collected 22 renal biopsies performed 16.2 +/- 10.6 months after the beginning of treatment; of which 21 had hypertension, mean proteinuria was 2.97 +/- 2.00 g/day and mean serum creatinine, 134 +/- 117 mu mol/L. Thrombotic microangiopathy (TMA) was observed in 21 biopsy specimens, sometimes associated with acute tubular necrosis (ATN; n = 4). TMA histological lesions were more important than the biological signs of TMA could suggest. Patients with ATN of >20% had higher serum creatinine levels than those with only TMA (231 versus 95 mu mol/L). Nephrin, podocin and synaptopodin were variably down-regulated in all renal biopsies. VEGF was down-regulated in all glomeruli. Conclusion. This study underlines the importance of regular clinical and biological cardiovascular and renal checking during all anti-VEGF therapies for cancer for early detection of renal dysfunction. Collaboration between oncologists and nephrologists is essential. In such cases, renal biopsy might help in appreciating the severity of the renal lesions and after multidisciplinary discussion whether or not it is safe to continue the treatment.