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PLoS One. 2017 Jan 12;12(1):e0169137. doi: 10.1371/journal.pone.0169137. eCollection 2017.

Increased Serum Sodium and Serum Osmolarity Are Independent Risk Factors for Developing Chronic Kidney Disease; 5 Year Cohort Study.

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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.
Tottori University Graduate School of Medical Sciences, Division of Regenerative Medicine and Therapeutics, Yonago, Japan.
Department of Pediatric Endocrinology, University of Colorado School of Medicine, Aurora, Colorado, United States of America.
Laboratory of Renal Physiopathology and Nephrology Dept, Instituto Nacional de Cardiología Ignacio Chávez, Mexico.



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.


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.


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).


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.

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Conflict of interest statement

Dr Johnson and Lanaspa have patents and patent applications related to blocking sugar and uric acid metabolism as a means for preventing or treating metabolic diseases. Dr Johnson, Lanaspa, Roncal-Jimenez, and Sanchez-Lozada are also members of a startup (Colorado Research Partners LLC) that is developing inhibitors of fructose metabolism. Dr Johnson is also on the Scientific Board of XORT therapeutics and of Amway. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

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