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Proof of concept: hypovolemic hyponatremia may precede and augment creatine kinase elevations during an ultramarathon



It is not known if exercise-associated hyponatremia (EAH) is a cause or consequence of exertional rhabdomyolysis (ER).We hypothesized that osmotic stress (EAH) coupled with mechanical stress (running) potentiated muscle cell breakdown (ER). This concept would be supported if a nadir in serum sodium concentration ([Na+]) temporally preceded peak creatine kinase levels (CK) during an ultramarathon run.


Fifteen participants ran ≥104 km and had blood drawn: prior to start; 53; 104 km; and 24-h post run. Serum [Na+], CK, urea, creatinine and estimated glomerular filtration rate (eGFR) were measured from serial blood samples. Two-way repeated-measures ANOVA was used to examine differences regarding both race distance and natremia status.


Ten of 15 participants demonstrated EAH (serum [Na+] <135 mmol/L) at least once during serial testing. Participants were categorized post hoc into one of three natremia groups based on lowest recorded [Na+]: (1) <129 mmol/L (n = 3; moderate EAH); (2) between 129 and 134 mmol/L (n = 7; mild EAH); and (3) >134 mmol/L (n = 5; normonatremia). Participants with lowest [Na+] demonstrated highest CK values at subsequent checkpoints. Significant natremia group differences noted at the 53 km point (p = 0.0002) for [Na+] while significant natremia group effect noted for CK seen at the 24-h post-finish testing point (p = 0.02). Significant natremia group effects noted for renal biomarkers, with the moderate EAH group documenting the lowest eGFR (p = 0.005), and highest serum urea (p = 0.0006) and creatinine (p < 0.0001) levels. Hyponatremic runners had lower post-race urine [Na+] than normonatremic runners (26 ± 15 vs. 89 ± 79 mmol/L; p = 0.03).


Preliminary data support the possibility that transient hypovolemic EAH may precede and augment CK during an ultramarathon.

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Acute kidney injury


Analysis of variance


Arginine vasopressin


Blood urea nitrogen


Creatine kinase


Glomerular filtration rate


Exercise-associated hyponatremia


Exertional rhabdomyolysis


Sodium concentration


Non-steroidal anti-inflammatory drugs


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Funding of AU$2000 was received from the GNW100s race organization committee. The authors would like to thank Dr Vanessa Cairns BSc, MBBS for considerable help in formulation of data collection, data input and proof reading; Dr Jonathan Brown BM, MRCGP, FRACGP for help in data collection; Dr Malcolm Jonathan King MBChB, MSc, FRACGP, FACSP for help in data collection; Royal Prince Alfred Hospital, Camperdown, Sydney, NSW; Immunology and Biochemistry Laboratories for blood sample analysis; Laverty Pathology for blood sample analyses. The authors declare no conflicts of interest.

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Correspondence to Tamara Hew-Butler.

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Communicated by Fabio Fischetti.

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Cairns, R.S., Hew-Butler, T. Proof of concept: hypovolemic hyponatremia may precede and augment creatine kinase elevations during an ultramarathon. Eur J Appl Physiol 116, 647–655 (2016). https://doi.org/10.1007/s00421-015-3324-4

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  • Acute kidney injury
  • Rhabdomyolysis
  • Dysnatremia