title: Kidney diseases associated with anti-vascular endothelial growth factor (VEGF): an 8-year observational study at a single center.
abstract: Expanded clinical experience with patients taking antiangiogenic compounds has come with increasing recognition of the renal adverse effects. Because renal histology is rarely sought in those patients, the renal consequences are underestimated. Antiangiogenic-treated-cancer patients, who had a renal biopsy for renal adverse effects from 2006 to 2013, were included in the current study. Clinical features and renal histologic findings were reviewed. Our cohort was 100 patients (58 women) with biopsy-proven kidney disease using anti-vascular endothelial growth factor (VEGF) therapy with a mean age of 59.8 years (range, 20-85 yr). Patients were referred for proteinuria, hypertension, and/or renal insufficiency. Kidney biopsy was performed 6.87 ± 7.18 months after the beginning of treatment. Seventy-three patients experienced renal thrombotic microangiopathy (TMA) and 27 patients had variable glomerulopathies, mainly minimal change disease and/or collapsing-like focal segmental glomerulosclerosis (MCN/cFSGS). MCN/cFSGS-like lesions developed mainly with tyrosine-kinase inhibitors, whereas TMA complicated anti-VEGF ligand. Thirty-one percent of TMA patients had proteinuria up to 1 g/24 h. Half of TMA cases are exclusively renal localized. Pathologic TMA features are intraglomerular exclusively. MCN/cFSGS glomeruli displayed a high abundance of KI-67, but synaptopodin was not detected. Conversely, TMA glomeruli exhibited a normal abundance of synaptopodin-like control, whereas KI-67 was absent. Median follow-up was 12 months (range, 1-80 mo). Fifty-four patients died due to cancer progression. Hypertension and proteinuria resolved following drug discontinuation and antihypertensive agents. No patient developed severe renal failure requiring dialysis. Drug continuation or reintroduction resulted in a more severe recurrence of TMA in 3 out of 4 patients requiring maintenance of anti-VEGF agents despite renal TMA. In conclusion, TMA and MCN/cFSGS are the most frequent forms of renal involvement under anti-VEGF therapy. Careful risk-benefit assessment for individual patients should take into account risk factors related to the host and the tumor.
authors.affiliation: From the Department of Nephrology (HI, VG, AB) and Pathology (PR), Pitié Salpêtrière Hospital, Paris; Department of Medical Oncology (BE, LD) and Gynecology (CL, PP), and Drug Development Department (DITEP) (RB, AH, JCS), Gustave Roussy Institute, VilleJuif; and Department of Nephrology (DS), UMRS 955 (DS), Henri Mondor Hospital, Creteil, France.
authors.forename: Hassan
authors.initials: H
authors.lastname: Izzedine
authors.forename: Bernard
authors.initials: B
authors.lastname: Escudier
authors.forename: Catherine
authors.initials: C
authors.lastname: Lhomme
authors.forename: Patricia
authors.initials: P
authors.lastname: Pautier
authors.forename: Philippe
authors.initials: P
authors.lastname: Rouvier
authors.forename: Victor
authors.initials: V
authors.lastname: Gueutin
authors.forename: Alain
authors.initials: A
authors.lastname: Baumelou
authors.forename: Lisa
authors.initials: L
authors.lastname: Derosa
authors.forename: Rastilav
authors.initials: R
authors.lastname: Bahleda
authors.forename: Antoine
authors.initials: A
authors.lastname: Hollebecque
authors.forename: Djillali
authors.initials: D
authors.lastname: Sahali
authors.forename: Jean Charles
authors.initials: JC
authors.lastname: Soria
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005923:Glomerulosclerosis, Focal Segmental / Q000139:chemically induced; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D009402:Nephrosis, Lipoid / Q000139:chemically induced; D011446:Prospective Studies; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D020794:Receptor Protein-Tyrosine Kinases / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*; D055815:Young Adult
chemical_list: D042461:Vascular Endothelial Growth Factor A; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases