Molecular determinants of sodium and water balance during early human development

Holtbäck, Ulla; Aperia, Anita

doi:10.1016/s1084-2756(03)00042-3

Cited by 59 publications

(41 citation statements)

References 48 publications

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“…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.…”

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confidence: 99%

Physiological Partial Aldosterone Resistance in Human Newborns

Martinerie

Pussard

L’Hélias³

et al. 2009

Pediatr Res

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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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confidence: 99%

Physiological Partial Aldosterone Resistance in Human Newborns

Martinerie

Pussard

L’Hélias³

et al. 2009

Pediatr Res

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“…18 We found a negative correlation between plasma sodium and UAE already during the first three days of life that may confirm the physiological partial aldosterone resistance in human neonates, due to a progressive increase of renal mineralocorticoid receptor expression level in the first days after birth, concurrently with renal maturation. 23,24 In the exploratory analysis we found a significant positive correlation between UAE and gestational age and birth …”

Section: Discussionmentioning

confidence: 80%

Early urinary aldosterone excretion in very low birth weight infants

Costa

Cota

Romagnoli

et al. 2012

J Renin Angiotensin Aldosterone Syst

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Hypothesis/Introduction: In the neonatal period, many factors may interfere with aldosterone production but data currently available are few and controversial. In this study we aim to assess the early urinary aldosterone excretion (UAE) in very low birth weight (VLBW) infants and to identify some possible clinical and biochemical variables that may influence this excretion. Materials and methods:We conducted a prospective study in 30 VLBW infants. Aldosterone was measured in the first 72 hours of life in the urine and plasma and urinary electrolytes were determined. Demographic and clinical data were also recorded.Results: The exploratory analysis showed that a significant positive correlation exists between UAE and gestational age and birth weight and that infants with respiratory distress syndrome have higher urinary aldosterone levels than infants without respiratory distress, but only plasma sodium resulted a significant independent factor that negatively influenced UAE at linear regression analysis (coefficient -0.02, 95% confidence interval [-0.03; -0.004]; adjusted R 2 0.33). Conclusions:The renin-angiotensin-aldosterone system of VLBW infants seems to be able, even immediately after birth, to respond to variations of plasma sodium concentrations; measurement of UAE constitutes an interesting method to determine aldosterone production, avoiding blood sampling in neonates so small and frail as VLBW infants.

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“…The integrity of the mineralocorticoid axis is particularly relevant in the neonatal period, where renal regulation of water and electrolyte balance is impaired due to immature tubular function (Holtback & Aperia 2003). Events such as prematurity or infections may lead to salt loss and dehydration, which can be further amplified by physiological partial resistance to aldosterone in the newborn (Martinerie et al 2009).…”

Section: Pseudohypoaldosteronism Typementioning

confidence: 99%

30 YEARS OF THE MINERALOCORTICOID RECEPTOR: Mineralocorticoid receptor mutations

Zennaro

Fernandes-Rosa

2017

Journal of Endocrinology

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Aldosterone and the mineralocorticoid receptor (MR) are key elements for maintaining fluid and electrolyte homeostasis as well as regulation of blood pressure. Loss-of-function mutations of the MR are responsible for renal pseudohypoaldosteronism type 1 (PHA1), a rare disease of mineralocorticoid resistance presenting in the newborn with weight loss, failure to thrive, vomiting and dehydration, associated with hyperkalemia and metabolic acidosis, despite extremely elevated levels of plasma renin and aldosterone. In contrast, a MR gain-of-function mutation has been associated with a familial form of inherited mineralocorticoid hypertension exacerbated by pregnancy. In addition to rare variants, frequent functional single nucleotide polymorphisms of the MR are associated with salt sensitivity, blood pressure, stress response and depression in the general population. This review will summarize our knowledge on MR mutations in PHA1, reporting our experience on the genetic diagnosis in a large number of patients performed in the last 10 years at a national reference center for the disease. We will also discuss the influence of rare MR variants on blood pressure and salt sensitivity as well as on stress and cognitive functions in the general population.

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Molecular determinants of sodium and water balance during early human development

Cited by 59 publications

References 48 publications

Physiological Partial Aldosterone Resistance in Human Newborns

Physiological Partial Aldosterone Resistance in Human Newborns

Early urinary aldosterone excretion in very low birth weight infants

30 YEARS OF THE MINERALOCORTICOID RECEPTOR: Mineralocorticoid receptor mutations

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