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 (r s = -0.17, p = 0.017). Stronger correlations were identified between serum C-reactive protein and copeptin (r s = -0.36, p < 0.0001) and between serum C-reactive protein and sodium (r s = 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.

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Malaria Journal
Department of Clinical Chemistry

Hoorn, E., van Wolfswinkel, M., Hesselink, D., de Rijke, Y., Koelewijn, R., van Hellemond, J., & van Genderen, P. (2012). Hyponatraemia in imported malaria: The pathophysiological role of vasopressin. Malaria Journal, 11. doi:10.1186/1475-2875-11-26