title: Increased Serum Sodium and Serum Osmolarity Are Independent Risk Factors for Developing Chronic Kidney Disease; 5 Year Cohort Study.
abstract: BACKGROUND
  Epidemics of chronic kidney disease (CKD) not due to diabetes mellitus (DM) or hypertension have been observed among individuals working in hot environments in several areas of the world. Experimental models have documented that recurrent heat stress and water restriction can lead to CKD, and the mechanism may be mediated by hyperosmolarity that activates pathways (vasopressin, aldose reductase-fructokinase) that induce renal injury. Here we tested the hypothesis that elevated serum sodium, which reflects serum osmolality, may be an independent risk factor for the development of CKD.
  
  
  METHODS
  This study was a large-scale, single-center, retrospective 5-year cohort study at Center for Preventive Medicine, St. Luke's International Hospital, Tokyo, Japan, between 2004 and 2009. We analyzed 13,201 subjects who underwent annual medical examination of which 12,041 subjects (age 35 to 85) without DM and/or CKD were enrolled. This analysis evaluated age, sex, body mass index, abdominal circumference, hypertension, dyslipidemia, hyperuricemia, fasting glucose, BUN, serum sodium, potassium, chloride and calculated serum osmolarity.
  
  
  RESULTS
  Elevated serum sodium was an independent risk factor for development of CKD (OR: 1.03, 95% CI, 1.00-1.07) after adjusted regression analysis with an 18 percent increased risk for every 5 mmol/L change in serum sodium. Calculated serum osmolarity was also an independent risk factor for CKD (OR: 1.04; 95% CI, 1.03-1.05) as was BUN (OR: 1.08; 95% CI, 1.06-1.10) (independent of serum creatinine).
  
  
  CONCLUSIONS
  Elevated serum sodium and calculated serum osmolarity are independent risk factors for developing CKD. This finding supports the role of limiting salt intake and preventing dehydration to reduce risk of CKD.
authors.affiliation: University of Colorado Denver, School of Medicine, Division of Renal Diseases and Hypertension, Aurora, Colorado, United States of America.|Toranomon Hospital, Department of Cardiology, Tokyo, Japan.|St. Luke's International Hospital, Cardiovascular Center, Tokyo, Japan.
authors.forename: Masanari
authors.initials: M
authors.lastname: Kuwabara
authors.affiliation: Tottori University Graduate School of Medical Sciences, Division of Regenerative Medicine and Therapeutics, Yonago, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Hisatome
authors.affiliation: University of Colorado Denver, School of Medicine, Division of Renal Diseases and Hypertension, Aurora, Colorado, United States of America.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Roncal-Jimenez
authors.affiliation: St. Luke's International Hospital, Cardiovascular Center, Tokyo, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Niwa
authors.affiliation: University of Colorado Denver, School of Medicine, Division of Renal Diseases and Hypertension, Aurora, Colorado, United States of America.
authors.forename: Ana
authors.initials: A
authors.lastname: Andres-Hernando
authors.affiliation: University of Colorado Denver, School of Medicine, Division of Renal Diseases and Hypertension, Aurora, Colorado, United States of America.
authors.forename: Thomas
authors.initials: T
authors.lastname: Jensen
authors.affiliation: Department of Pediatric Endocrinology, University of Colorado School of Medicine, Aurora, Colorado, United States of America.
authors.forename: Petter
authors.initials: P
authors.lastname: Bjornstad
authors.affiliation: University of Colorado Denver, School of Medicine, Division of Renal Diseases and Hypertension, Aurora, Colorado, United States of America.
authors.forename: Tamara
authors.initials: T
authors.lastname: Milagres
authors.affiliation: University of Colorado Denver, School of Medicine, Division of Renal Diseases and Hypertension, Aurora, Colorado, United States of America.
authors.forename: Christina
authors.initials: C
authors.lastname: Cicerchi
authors.affiliation: University of Colorado Denver, School of Medicine, Division of Renal Diseases and Hypertension, Aurora, Colorado, United States of America.
authors.forename: Zhilin
authors.initials: Z
authors.lastname: Song
authors.affiliation: University of Colorado Denver, School of Medicine, Division of Renal Diseases and Hypertension, Aurora, Colorado, United States of America.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Garcia
authors.affiliation: Laboratory of Renal Physiopathology and Nephrology Dept, Instituto Nacional de Cardiología Ignacio Chávez, Mexico.
authors.forename: Laura G
authors.initials: LG
authors.lastname: Sánchez-Lozada
authors.affiliation: Toranomon Hospital, Department of Cardiology, Tokyo, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Ohno
authors.affiliation: University of Colorado Denver, School of Medicine, Division of Renal Diseases and Hypertension, Aurora, Colorado, United States of America.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Lanaspa
authors.affiliation: University of Colorado Denver, School of Medicine, Division of Renal Diseases and Hypertension, Aurora, Colorado, United States of America.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Johnson
mesh_terms: D000293:Adolescent; D000328:Adult; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D015995:Prevalence; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000453:epidemiology / Q000209:etiology; D012189:Retrospective Studies; D012307:Risk Factors; D012737:Sex Factors; D012964:Sodium / Q000097:blood*; D014545:Urinary Calculi / Q000097:blood / Q000150:complications / Q000453:epidemiology
chemical_list: D012964:Sodium