title: Sunitinib- and sorafenib-induced nephrotic syndrome in a patient with gastrointestinal stromal tumor.
abstract: OBJECTIVE
  To report a case of nephrotic syndrome (NS) induced by both sunitinib and sorafenib therapy.
  
  
  METHODS
  A 61-year-old woman with metastatic gastrointestinal stromal tumor (GIST) presented with NS and hypertension following therapy with sunitinib 400 mg/day. Because of grade 3 toxicity, the drug was discontinued. After sunitinib discontinuation, NS and hypertension resolved. However, NS recurred on rechallenge. A similar picture developed following therapy with sorafenib 800 mg/day. A renal biopsy revealed a focal segmental glomerulosclerosis (FSGS). A few months after sorafenib cessation, resolution of NS and hypertension was again achieved.
  
  
  CONCLUSIONS
  Several cases of NS have been reported among patients receiving sunitinib and sorafenib. However, renal histopathologic data were obtained in only a few patients. Although biopsy-proven cases of FSGS associated with sunitinib have been reported, this is, to our knowledge, the first reported case of biopsy-proven FSGS associated with sorafenib. The Naranjo probability scale indicated probable causality for NS developing with sorafenib, and definite causality with sunitinib. The clinical and histopathologic findings have led us to agree with the class effect proposal that all antiangiogenic drugs share a similar toxicity profile. Evidence supporting this hypothesis includes worsening of hypertension and proteinuria by both drugs, with full recovery occurring within a few months after cessation of the drugs, which favors the role of vascular endothelial growth factor receptor inhibition in FSGS development.
  
  
  CONCLUSIONS
  The clinical adverse spectrum of antiangiogenic drugs may be broader than initially observed because of a lack of renal biopsy data and routine screening for proteinuria. It can be speculated that proteinuria, as well as hypertension, is a class effect of all antiangiogenic drugs.
authors.affiliation: Gazi University Faculty of Medicine, Besevler, Ankara, Turkey. turan.nedim@hotmail.com
authors.forename: Nedim
authors.initials: N
authors.lastname: Turan
authors.forename: Mustafa
authors.initials: M
authors.lastname: Benekli
authors.forename: Selcuk Cemil
authors.initials: SC
authors.lastname: Ozturk
authors.forename: Salih
authors.initials: S
authors.lastname: Inal
authors.forename: Leyla
authors.initials: L
authors.lastname: Memis
authors.forename: Galip
authors.initials: G
authors.lastname: Guz
authors.forename: Bulent
authors.initials: B
authors.lastname: Cetin
authors.forename: Suleyman
authors.initials: S
authors.lastname: Buyukberber
mesh_terms: D020533:Angiogenesis Inhibitors / Q000009:adverse effects*; D001557:Benzenesulfonates / Q000009:adverse effects*; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy / Q000473:pathology; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D007211:Indoles / Q000009:adverse effects*; D008875:Middle Aged; D009404:Nephrotic Syndrome / Q000139:chemically induced* / Q000473:pathology; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011725:Pyridines / Q000009:adverse effects*; D011758:Pyrroles / Q000009:adverse effects*; D000077157:Sorafenib; D000077210:Sunitinib
chemical_list: D020533:Angiogenesis Inhibitors; D001557:Benzenesulfonates; D007211:Indoles; D010671:Phenylurea Compounds; D011725:Pyridines; D011758:Pyrroles; D009536:Niacinamide; D000077157:Sorafenib; D000077210:Sunitinib