All New Antiangiogenic Therapies Can Induce “Preeclampsia-Like Syndrome"
Nathalie Rioux-Leclercq, Thibault Dolley-Hitze, Nolwen Lorcy, Marc-Antoine Belaud-Rotureau, Florence Jouan, Cecile Vigneau. CHU Pontchaillou, Rennes Cedex 9, France; Institut Génétique et Développement de Rennes, Rennes, France
Background: AntiVEGF argeted therapies are used in metastatic carcinomas. However, renal side effects seem to be underestimated. According to the clinical and physiopathological similitaries between preeclampsia and renal side effects of anti-VEGF therapies, we postulated that glomerular protein abnormalities described in the preeclampsia might be seen in kidneys developing renal side effects under antiangiogenic drugs. We report a series of patients treated by anti-VEGF therapies for cancer and undergoing a renal biopsy (RB) because of renal side effects.
Design: RB performed in several centers in France for proteinuria or renal failure under antiangiogenic drugs have been collected in Rennes. 17 RB and 5 kidneys samples from nephrectomy under antiangiogenic drugs have been included.
Results: Patients presented a proteinuria and/or renal failure and a hypertension after/under antiangiogenic treatment. Renal biopsies have been realized mainly 14,2 +/- 9,7 months after treatment. 15/17 patients were treated by RAS blockers at the time of the biopsy. Mean proteinuria was 3.14 +/-2.4 g/d and mean creatininemia was 146 +/- 128 µmol/L. There was mild or no biological sign of (thrombotic microangiopathy)TMA.
For the 5 kidneys treated by antiangiogenic therapies before surgery, none but one exhibited proteinuria nor hypertension. All but one kidney showed chronic TMA, 3 with acute microthrombosis and 5 with acute tubular necrosis (ATN). Serum creatininemia of patients with more than 20% ATN was higher than serum creatinemia of patients with only glomerular TMA. All of the biopsies from nephrectomies, showed only ATN due to surgical clampage. all RB showed a mild to dramatic decrease of nephrin, podocin and synaptopodin immunostained expression. Even when the patient was treated by a RAS blocker, there was no re-expression of those proteins. Moreover, there is no correlation between expression of these proteins and existence of ATN.
Conclusions: Our series underlines the importance of regular checking by arterial tension, urinary dipstick and creatininemia measurements for all patients treated by any anti-VEGF therapy. This checking might allow to detect early TMA, and allow or not the safe continuation of the therapy.
Category: Genitourinary (including renal tumors)
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 166, Tuesday Morning