Predictors of nonresponse to fluid restriction in hyponatraemia due to the syndrome of inappropriate antidiuresis

J Intern Med. 2016 Dec;280(6):609-617. doi: 10.1111/joim.12532. Epub 2016 Aug 1.


Background: Fluid restriction (FR), the first-line treatment for hyponatraemia due to the syndrome of inappropriate antidiuresis (SIAD), often does not lead to successful correction of hyponatraemia. Therefore, predictive markers of treatment response are desirable. We evaluated routinely measured serum (s) and urine (u) parameters, s-copeptin and s-mid-regional pro-atrial natriuretic peptide (s-MR-proANP), as possible predictors of FR response.

Methods: In this prospective observational study, we included patients with profound hyponatraemia (s-sodium <125 mmol L-1 ) due to SIAD. Patients were classified as FR responders (increase in s-sodium concentration of >3 mmol L-1 within 24 h) or nonresponders (increase of ≤3 mmol L-1 within 24 h). Initial laboratory parameters were compared between groups with logistic regression analysis.

Results: Of 106 SIAD patients analysed, 82 underwent treatment with FR; 48 (59%) patients showed a successful response to FR and 34 (41%) were considered nonresponders. High levels of u-sodium and u-osmolality were significantly associated with nonresponse to FR [odds ratio (OR) 15.0, 95% confidence interval (CI) 2.4-95.8, P = 0.004 and OR 34.8, 95% CI 1.2-1038.8, P = 0.041, respectively). The association of u-sodium and nonresponse remained significant also after adjustment for diuretic use. Lower levels of s-MR-proANP were associated with nonresponse (OR 0.03, 95% CI 0.003-0.3, P = 0.004), whereas s-copeptin was not significantly associated with response to FR.

Conclusion: Easily measured laboratory parameters, especially u-sodium, correlate with therapeutic response and identify patients most likely to fail to respond to FR. Measurement of these parameters may facilitate early treatment choice in patients with SIAD.

Keywords: SIAD; fluid restriction; hyponatraemia; predictors; syndrome of inappropriate antidiuresis.

Publication types

  • Observational Study

MeSH terms

  • Atrial Natriuretic Factor / blood
  • Biomarkers / blood
  • Biomarkers / urine
  • Glycopeptides / blood
  • Humans
  • Hyponatremia / etiology
  • Hyponatremia / metabolism
  • Hyponatremia / therapy*
  • Inappropriate ADH Syndrome / complications*
  • Osmolar Concentration
  • Prospective Studies
  • Sodium / urine
  • Urine


  • Biomarkers
  • Glycopeptides
  • copeptins
  • midregional pro-atrial natriuretic peptide, human
  • Atrial Natriuretic Factor
  • Sodium