High plasma mid-regional pro-adrenomedullin levels in children with severe dengue virus infections.
BACKGROUND
Dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) is characterized by hemorrhage, plasma leakage and shock. Adrenomedullin and vasopressin are vaso-active hormones that mediate endothelial permeability, vascular tone and water balance and may therefore play a role during DHF/DSS. Adrenomedullin reduces endothelial permeability and has vasodilatory properties, while vasopressin is a potent vasoconstrictor with anti-diuretic effects.


OBJECTIVE
To determine mid-regional pro-adrenomedullin (MR-proADM) and copeptin, which are reliable and stable markers for adrenomedullin and vasopressin response, respectively, and relate their plasma concentrations to outcome and markers of plasma leakage in Indonesian children with DHF and DSS.


METHODS
In this observational cohort study Indonesian children with DHF/DSS were enrolled. On study days 0 and 2, plasma MR-proADM and copeptin concentrations as well as parameters of plasma leakage were determined. Plasma MR-proADM and copeptin concentrations were compared to values of healthy controls.


RESULTS
MR-proADM was increased in both DHF (n=43) and DSS (n=28) vs. controls (n=17), with median (IQR) values of 0.47 (0.40-0.68), 0.56 (0.44-1.00) vs. 0.22 (0.19-0.29) nmol/L, respectively. Additionally, MR-proADM correlated with signs of increased vascular leakage such as low albumin and increased pleural effusion. Copeptin concentrations showed no significant changes as compared to controls.


CONCLUSIONS
MR-proADM concentrations are elevated in children with DHF and DSS and correlate with the severity of plasma leakage, in contrast to copeptin concentrations. We speculate that adrenomedullin has a functional role in limiting endothelial hyperpermeability during DHF/DSS. Finally, MR-proADM may be a candidate biomarker to predict development of DHF/DSS.
Michels
Meta
M
Department of General Internal Medicine, Radboud University Nijmegen Medical Center, The Netherlands. M.Michels@aig.umcn.nl
Djamiatun
Kis
K
Faradz
Sultana M H
SM
Koenders
Mieke M J F
MM
de Mast
Quirijn
Q
van der Ven
André J A M
AJ
D053607:Adrenomedullin / Q000097:blood*; D002199:Capillary Permeability; D002648:Child; D015331:Cohort Studies; D003716:Dengue Virus / Q000502:physiology; D005260:Female; D006020:Glycopeptides / Q000097:blood; D006801:Humans; D008297:Male; D012709:Serum Albumin / Q000378:metabolism; D019595:Severe Dengue / Q000097:blood* / Q000503:physiopathology* / Q000821:virology
D006020:Glycopeptides; D012709:Serum Albumin; C048197:copeptins; D053607:Adrenomedullin