MO238CHALLENGING BEVACIZUMAB RELATED KIDNEY DAMAGE: A SUCCESSFUL STRATEGY BY THE NEPHROLOGIST

Background Renal complications in cancer patients are frequently associated with chemotherapy, immunotherapy and targeted drugs. Inhibitors of vascular endothelial growth factor(anti-VEGF) advent has permitted a significant survival improvement in metastatic patients, promising less renal complications than conventional chemotherapy .Indeed, direct nephrotoxicity is not typical, but immune-mediated glomerular damage is increasingly reported as a common complication of anti-VEGFs.The blockade of VEGF in podocytes mightimpair the filtration barrierintegrity leading to proteinuria appearance.In addition, anti-VEGFs activate NFkb triggering pro-inflammatory cytokines. The lack of integrity of the filtration membrane and the inflammatory milieu could probably lead to the exposure of normally unexposed antigens and consequently predispose, by a mimicry mechanism, to autoantibodies and immunocomplex formation/deposition and renal damage occurrence. Case report We report the case of a 59-year-old male with a history of adenocarcinoma of sigma-rectumand peritoneal carcinosis, who underwent several cycles of chemotherapy. In 2015, the patient presented with gastro-intestinal obstruction. A laparoscopic rectal resection was first performed, followed by colostomy and two cycles of the FOL-FOX protocol. Between 2016 and 2019, due to disease progression, the patient received FOLFIRI protocol and, subsequently, the anti-VEGF Bevacizumab. During the treatment course, laboratory tests documented moderate proteinuria (1 g/day approximately) and normal kidney function. End of 2019,due to a creatinine rise to 1.6 mg/dl, Bevacizumab was suspended. However, in the next three months the kidney function continued to worsen and reached a level of 3.2 mg/dl. The patient was referred to our Nephrology Unit and admitted to the ward showing an increase of 24 h proteinuria to 2 g/day with stable high creatinine and normal renal ultrasound parameters. In the suspect of a dehydration, patient was infused with saline solution without any significant GFR improvement. Suspecting an anti-VEGF mediated glomerulopathy, we checked the patient for an autoimmunity panel and found a positivity for ANA anti- Ro, anti Mi-2 and ASMA. A renal biopsy was not performed because the patient did not release the consent and a 2-month course of prednisone 25 mg/day was introduced and successively tapered to a maintenance dose of 5 mg/day. A prompt improvement of the kidney function (creatinine decreased to 1.5 mg/dl) and proteinuria (240 mg/24h)was observed and allowed a new oncological evaluation in order to start a new cycle of targeted-therapy. Conclusion Our case report suggests the need for an accurate investigation of the pathophysiological mechanisms of kidney damage linked to anti-VEGF agents. Moreover, based on our clinical experience, it appears that the multidisciplinary approach, with a key role of the nephrologist, to oncologic patients on anti-VEGF agents complicated with renal damage, is fundamental for achieving a double goal: oncologic therapy maintenance and renal function preservation.