title: Impact of hyponatremia on survival of patients with metastatic renal cell carcinoma treated with molecular targeted therapy.
abstract: OBJECTIVE
  Hyponatremia is reported to be associated with poor survival in localized renal cell carcinoma and metastatic renal cell carcinoma treated with immunotherapy. However, there are no reports on the relationship between hyponatremia and prognosis of metastatic renal cell carcinoma treated with molecular targeted therapy. We evaluated the prognostic significance of hyponatremia in metastatic renal cell carcinoma treated with molecular targeted therapy as first-line therapy.
  
  
  METHODS
  We retrospectively analyzed a database comprising 87 patients treated from April 2008 to July 2011 with sorafenib or sunitinib as first-line therapy for metastatic renal cell carcinoma. Patients were divided into three groups according to serum sodium level: severe hyponatremia (≤134 mEq/L), mild hyponatremia (135-137 mEq/L) and normal natremia (≥138 mEq/L).
  
  
  RESULTS
  Median cancer-specific survival time was 8.8 months in the patients with severe and mild hyponatremia, and 32.6 months in the patients with normal natremia (P < 0.001). Multivariate analysis showed severe and mild hyponatremia to be significantly associated with cancer-specific survival (hazard ratio 6.228; 95% confidence interval 2.161-17.947, P = 0.001; hazard ratio 3.374; 95% confidence interval 1.294-8.798, P = 0.013), respectively. Neutrophilia and high C-reactive protein level (C-reactive protein ≥1.0 mg/dL) were significant prognostic factors to predict inferior cancer-specific survival. In Harrell's concordance index calculation, hyponatremia could significantly improve the predictive accuracy for estimation of survival probability (P = 0.028).
  
  
  CONCLUSIONS
  Hyponatremia (<138 mEq/L), neutrophilia and high C-reactive protein levels seem to represent significant predictive factors for cancer-specific survival in metastatic renal cell carcinoma patients treated with molecular targeted therapy as first line therapy. Furthermore, hyponatremia might be significantly associated with chronic inflammation and tumor aggressiveness.
authors.affiliation: Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Atsunari
authors.initials: A
authors.lastname: Kawashima
authors.forename: Akira
authors.initials: A
authors.lastname: Tsujimura
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takayama
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Arai
authors.forename: Mikio
authors.initials: M
authors.lastname: Nin
authors.forename: Go
authors.initials: G
authors.lastname: Tanigawa
authors.forename: Motohide
authors.initials: M
authors.lastname: Uemura
authors.forename: Yasutomo
authors.initials: Y
authors.lastname: Nakai
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nishimura
authors.forename: Norio
authors.initials: N
authors.lastname: Nonomura
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000556:secondary*; D002097:C-Reactive Protein / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000150:complications / Q000188:drug therapy* / Q000556:secondary; D016001:Confidence Intervals; D005260:Female; D006801:Humans; D007010:Hyponatremia / Q000150:complications*; D007211:Indoles / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D007964:Leukocytosis / Q000150:complications; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D015999:Multivariate Analysis; D009504:Neutrophils; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D011379:Prognosis; D016016:Proportional Hazards Models; D011758:Pyrroles / Q000627:therapeutic use*; D012189:Retrospective Studies; D012720:Severity of Illness Index; D012964:Sodium / Q000097:blood; D000077157:Sorafenib; D000077210:Sunitinib
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D010671:Phenylurea Compounds; D011758:Pyrroles; D009536:Niacinamide; D002097:C-Reactive Protein; D012964:Sodium; D000077157:Sorafenib; D000077210:Sunitinib