Physiological Partial Aldosterone Resistance in Human Newborns

Abstract

ABSTRACT:In the neonatal period, the human kidney is characterized by an impaired ability to regulate water and sodium homeostasis, resembling partial aldosterone resistance. The aim of our study was to assess this hormonal insensitivity in newborn infants and to determine its relationship with neonatal sodium handling. We conducted a prospective study in 48 healthy newborns and their mothers. Aldosterone, renin, and electrolyte concentrations were measured in umbilical cords and in maternal plasma. Urinary aldosterone concentrations and sodium excretion were determined at urination within 24 h after birth. A significant difference was observed between aldosterone and renin levels in newborn infants compared with their mothers (817 Ϯ 73 versus 575 Ϯ 55 pg/mL and 79 Ϯ 10 versus 15 Ϯ 2 pg/mL, respectively, p Ͻ 0.001). This hyperactivation of the renin-angiotensin-aldosterone system was associated with hyponatremia and hyperkalemia in the newborn infants, and high urinary sodium loss, consistent with a partial aldosterone resistance at birth. Unlike plasma aldosterone, urinary aldosterone concentration was found highly correlated with plasma potassium concentrations, thus representing the best index for accurate evaluation of mineralocorticoid sensitivity. Our study represents a comprehensive characterization of the renin-aldosterone axis in newborn infants and provides evidence for physiologic partial aldosterone resistance in the neonatal period. (Pediatr Res 66: 323-328, 2009) T he human kidney displays a tubular immaturity at birth, with sodium waste, responsible for a negative sodium balance, and an impaired ability to reabsorb water (1), which is aggravated under circumstances such as prematurity, pyelonephritis, and gastroenteritis (2). This inability to maintain homeostatic functions is a major problem encountered by pediatricians, most notably in preterm infants. Indeed, the challenge is to find a balance between the lethal risk of dehydration and the associated morbidity of excessive hydromineral supplementation, contributing to severe complications such as intraventricular hemorrhage and bronchopulmonary dysplasia (3). A better understanding of water and sodium regulation in the neonatal period is a prerequisite to propose new therapeutic strategies for the management of preterm infants.Sodium reabsorption is mainly controlled by aldosterone, a steroid hormone synthesized in the zona glomerulosa of the adrenal gland, secondary to renin stimulation via angiotensin II and to potassium stimulation (4). In the distal nephron, aldosterone, by binding to its receptor, the mineralocorticoid receptor, a transcription factor (5), tightly regulates the expression and the activity of several transport proteins implicated in sodium, potassium, and water homeostasis, as the alpha subunit of the epithelial sodium channel (6), the Na-KATPase (7), and the aquaporin 2 (8). A possible role of a partial and transient tubular unresponsiveness to this hormone has been suggested to account for sodium waste in neonates (9,10)....

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“…After the period of physiologic aldosterone resistance (20), each individual presented with life-threatening salt-loss within the second week of life. In most patients, CAH was initially suspected as it is the most common cause of neonatal onset of salt-losing crisis.…”

A New Presentation of the Chimeric CYP11B1/CYP11B2 Gene With Low Prevalence of Primary Aldosteronism and Atypical Gene Segregation Pattern

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Early urinary aldosterone excretion in very low birth weight infants

“…These authors found that in a population of 48 term neonates urinary aldosterone, unlike plasma aldosterone, was significantly and negatively correlated to the plasma potassium, leading to the conclusion that aldosterone participates in the control of potassium balance and that determination of urinary aldosterone levels constitutes an interesting non-invasive method to investigate aldosterone sensitivity in preterm and full-term infants. 19 In the neonatal period, several clinical and biochemical variables, such as gestational age, birth weight, plasma electrolytes, drugs and degree of illness, may interfere with aldosterone production.…”