Background: Tubular immaturity, responsible for sodium wasting, is critical during the neonatal period, particularly in preterm neonates. This relates to partial renal aldosterone resistance (Martinerie, Ped Res 2009), coincident with low tubular expression of the mineralocorticoid receptor in newborns (Martinerie, Endocrinology 2009).
Objective and methods: Our clinical trial (NCT01176162) aimed to assess aldosterone resistance in neonates according to gestational age and during a 1-year postnatal follow-up period, by measuring urinary aldosterone concentration (UAC) and its correlation to the urinary Na/K ratio as an index of renal aldosterone sensitivity.
Results: We enrolled 170 newborns prospectively, classified into three groups: <33 GW (gestational weeks) (52 patients), 3336 GW (69 patients), >37 GW (49 patients). Plasma aldosterone levels measured from umbilical cord blood samples were very high in the >37 GW group (1001±98 pg/ml) and decreased significantly with gestational age (583±48 and 380±55 pg/ml in the 3336 and <33 GW groups, respectively, P<0.0001). This was associated with an increase in renin levels (from 81±10 pg/ml in the >37 GW group to 135±22 pg/ml in the <33 GW group), suggesting an aldosterone biosynthesis/secretion defect in preterms. UAC followed a similar pattern (from 20.2±3.2 g/mmol urinary creatinine in term neonates to 8.8±1.2 in preterms, P<0.0001) significantly correlated with plasma aldosterone levels in all groups (P<0.0001), demonstrating its accuracy as a non-invasive index of aldosterone secretion. Renal aldosterone resistance was demonstrated in all groups given the lack of correlation between UAC and the urinary Na/K ratio, and high sodium wasting at birth in very preterm infants. Renal aldosterone responsiveness appears in term infants at 1 month of age (P=0.02) while renal aldosterone insensitivity persists in the preterm groups beyond 3 months.
Conclusion: These results uncover the mechanism of sodium wasting in preterm neonates and underscore new potential therapeutic management based on UAC measurement.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology