title: Hyponatraemia in imported malaria: the pathophysiological role of vasopressin.
abstract: BACKGROUND
  In the pathophysiology of hyponatraemia in malaria, the relative contribution of appropriate and inappropriate arginine vasopressin (AVP) release is unknown; the trigger for inappropriate AVP release is also unknown.
  
  
  METHODS
  Serum copeptin, a stable and sensitive marker for AVP release, was analysed in a large cohort of patients with imported malaria (204 patients) and in a small prospective substudy (23 patients) in which urine sodium and osmolality were also available. Hyponatraemia was classified as mild (serum sodium 131-134 mmol/l) and moderate-to-severe (< 131 mmol/l).
  
  
  RESULTS
  Serum copeptin on admission was higher in patients with moderate-to-severe hyponatraemia (median 18.5 pmol/L) compared with normonatraemic patients (12.7 pmol/L, p < 0.05). Despite prompt fluid resuscitation, the time to normalization of serum sodium was longer in patients with moderate-to-severe hyponatraemia (median 2.9 days) than in patients with mild hyponatraemia (median 1.7 days, p < 0.001). A poor correlation was found between serum sodium and copeptin levels on admission (rs = -0.17, p = 0.017). Stronger correlations were identified between serum C-reactive protein and copeptin (rs = -0.36, p < 0.0001) and between serum C-reactive protein and sodium (rs = 0.33, p < 0.0001). Data from the sub-study suggested inappropriate AVP release in seven of 13 hyponatraemic malaria patients; these patients had significantly higher body temperatures on admission.
  
  
  CONCLUSIONS
  In hyponatraemic patients with imported malaria, AVP release was uniformly increased and was either appropriate or inappropriate. Although the exact trigger for inappropriate AVP release remains unknown, the higher body temperatures, correlations with C-reactive protein and long normalization times of serum sodium, suggest an important role of the host inflammatory response to the invading malaria parasite.
authors.affiliation: Department of Nephrology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Ewout J
authors.initials: EJ
authors.lastname: Hoorn
authors.forename: Marlies E
authors.initials: ME
authors.lastname: van Wolfswinkel
authors.forename: Dennis A
authors.initials: DA
authors.lastname: Hesselink
authors.forename: Yolanda B
authors.initials: YB
authors.lastname: de Rijke
authors.forename: Rob
authors.initials: R
authors.lastname: Koelewijn
authors.forename: Jaap J
authors.initials: JJ
authors.lastname: van Hellemond
authors.forename: Perry J J
authors.initials: PJ
authors.lastname: van Genderen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001127:Arginine Vasopressin / Q000378:metabolism*; D002648:Child; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007010:Hyponatremia / Q000175:diagnosis* / Q000503:physiopathology*; D008288:Malaria / Q000150:complications* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D011446:Prospective Studies; D012720:Severity of Illness Index; D012964:Sodium / Q000032:analysis; D014556:Urine / Q000737:chemistry; D055815:Young Adult
chemical_list: D001127:Arginine Vasopressin; D012964:Sodium