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Risk factors for sodium overcorrection in non-hypovolemic hyponatremia patients treated with tolvaptan

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In this study, the risk factors associated with sodium overcorrection were investigated with an optimal cutoff for baseline serum sodium for use in daily clinical practice.


Electronic medical records of patients who received tolvaptan for non-hypovolemic hyponatremia were reviewed. Demographic and clinical data including age, sex, weight, height, comorbidity, cause of hyponatremia, hypertonic saline use, and comedication were collected. Baseline laboratory parameters measured included serum sodium, serum potassium, serum creatinine, blood urea nitrogen, serum tonicity, ALT, AST, and urine osmolality. The primary outcome was the overcorrection of serum sodium, which was defined as an increase in serum sodium by more than 10 mmol/L in 24 h.


From a total of 77 patients included in the analysis, 24 (31.2%) showed sodium overcorrection (> 10 mmol/L/24 h); 2 (2.6%) in heart failure cohort, 17 (22.1%) in SIADH cohort, and 5 (6.5%) in unknown cause cohort. More than half of patients (51.9%) were administered hypertonic saline prior to tolvaptan. Hypertension, cancer, diuretics, baseline serum sodium, and SIADH were associated with the risk of overcorrection in the univariable analysis. Significant factors for the overcorrection from multivariable analysis were lower body mass index, presence of cancer (adjusted odds ratio, 10.87; 95% CI, 1.23–96.44), and lower serum sodium at baseline (adjusted odds ratio, 0.76 for every 1 mEq/L increase; 95% CI, 0.61–0.94).


The overcorrection of hyponatremia in non-hypovolemic patients treated with tolvaptan was significantly associated with lower body mass index, presence of cancer, and lower serum sodium at baseline. In subgroup analysis using SIADH patients, baseline sodium and cancer were found to be significant factors of overcorrection.

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This research was supported by the Medical Research Center Program (2017R1A5A2015541) of the National Research Foundation of Korea (NRF) funded by the Korean government (MSIP).

Author information

All authors have contributed significantly to the work and have read and approved the manuscript for publication. Yukyung Kim and Hye Sun Gwak were responsible for the study concept and design. Yukyung Kim and Nari Lee participated in data collection. Nari Lee and Kyung Eun Lee analyzed the data. Kyung Eun Lee and Hye Sun Gwak contributed to the manuscript writing and discussion.

Correspondence to Kyung Eun Lee or Hye Sun Gwak.

Ethics declarations

This study was approved by the Institutional Review Board of the Catholic University of Korea Seoul St. Mary’s Hospital (IRB number KC19RESI0327).

Conflict of interest

The authors declare that there is no conflict of interest.

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The datasets during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Kim, Y., Lee, N., Lee, K.E. et al. Risk factors for sodium overcorrection in non-hypovolemic hyponatremia patients treated with tolvaptan. Eur J Clin Pharmacol (2020). https://doi.org/10.1007/s00228-020-02848-6

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  • Hyponatremia
  • Overcorrection
  • Tolvaptan
  • Serum sodium