title: Risk factors of proteinuria in renal cell carcinoma patients treated with VEGF inhibitors: a secondary analysis of pooled clinical trial data.
abstract: Proteinuria is a common adverse effect of vascular endothelial growth factor targeted agents, particularly in metastatic renal cell carcinoma (mRCC). However, risk factors for proteinuria are poorly defined.
  
  
  
  Data on 1392 mRCC patients using pazopanib or sunitinib were pooled from two Phase-III clinical trials. Risk factors and prognostic effect of on-therapy proteinuria were evaluated by Cox proportional hazards regression.
  
  
  
  Any-grade (1-4) and grade 3/4 proteinuria incidence were 15.0% and 3.7%, respectively. Asian ethnicity, diabetes, baseline systolic blood pressure (SBP), pre-existing grade 1 proteinuria and prior nephrectomy were significant independent predictors of either any-grade or grade 3/4 proteinuria. Proteinuria, particularly grade 3/4 (adjusted hazard ratio 0.53 (95% confidence interval 0.30-0.92)), was associated with improved overall survival.
  
  
  
  In mRCC patients using pazopanib or sunitinib, Asian ethnicity, diabetes, SBP, pre-existing proteinuria and prior nephrectomy were independent predictors of on-therapy proteinuria, which was associated with improved survival.
authors.affiliation: Department of Clinical Pharmacology, School of Medicine, Flinders University, Adelaide, South Australia 5042, Australia.|Flinders Centre for Innovation in Cancer, School of Medicine, Flinders University, Adelaide, South Australia 5042, Australia.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Sorich
authors.affiliation: Department of Clinical Pharmacology, School of Medicine, Flinders University, Adelaide, South Australia 5042, Australia.|Flinders Centre for Innovation in Cancer, School of Medicine, Flinders University, Adelaide, South Australia 5042, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Rowland
authors.affiliation: Flinders Centre for Innovation in Cancer, School of Medicine, Flinders University, Adelaide, South Australia 5042, Australia.
authors.forename: Ganessan
authors.initials: G
authors.lastname: Kichenadasse
authors.affiliation: Flinders Centre for Epidemiology and Biostatistics, School of Medicine, Flinders University, Adelaide, South Australia 5042, Australia.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Woodman
authors.affiliation: Department of Clinical Pharmacology, School of Medicine, Flinders University, Adelaide, South Australia 5042, Australia.
authors.forename: Arduino A
authors.initials: AA
authors.lastname: Mangoni
mesh_terms: D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000652:urine*; D005260:Female; D006801:Humans; D007191:Indazoles; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000652:urine*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011507:Proteinuria / Q000139:chemically induced*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use*; D012307:Risk Factors; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*; D000077210:Sunitinib; D016019:Survival Analysis; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
chemical_list: D007191:Indazoles; D007211:Indoles; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C516667:pazopanib; D000077210:Sunitinib