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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE  
Year : 2016  |  Volume : 27  |  Issue : 4  |  Page : 726-732
Evaluation of aldosterone excretion in very low birth weight infants


1 Department of Pediatrics, Faculty of Medicine, El-Minia University, Cairo, Egypt
2 Department of Biochemistry, Faculty of Medicine, El-Minia University, Cairo, Egypt

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Date of Web Publication5-Jul-2016
 

   Abstract 

Data about aldosterone production and excretion in the neonatal period are still few and controversial. Our objectives are to assess urinary aldosterone excretion (UAE) in very low birth weight (VLBW) infants and to identify clinical and biochemical variables that may influence this excretion. Thirty VLBW infants (14 males and 16 females), their gestational age <32 weeks and body weight <1500 g, were included in the study. Demographic and clinical data were recorded, within the first 72 h of life and urine and blood samples were collected for the measurement of urinary aldosterone and serum potassium, sodium, and chloride. The mean UAE value was 0.176 ± 0.05 μg/24 h and the mean absolute UAE was 1906 ± 271 pg/mL. There was a statistically significant positive correlation between UAE and gestational age and birth weight; also, infants with respiratory distress syndrome had higher urinary aldosterone levels than infants without respiratory distress. Only plasma sodium was a significant independent factor that negatively influenced UAE on linear regression analysis. 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 in VLBW infants.

How to cite this article:
Abdel Mohsen AH, Taha G, Kamel BA, Maksood MA. Evaluation of aldosterone excretion in very low birth weight infants. Saudi J Kidney Dis Transpl 2016;27:726-32

How to cite this URL:
Abdel Mohsen AH, Taha G, Kamel BA, Maksood MA. Evaluation of aldosterone excretion in very low birth weight infants. Saudi J Kidney Dis Transpl [serial online] 2016 [cited 2021 Dec 9];27:726-32. Available from: https://www.sjkdt.org/text.asp?2016/27/4/726/185234

   Introduction Top


Aldosterone was discovered in 1952 by Simpson et al and is produced in the outer (glomerulosa) cell layer of the adrenal cortex. [1] Aldosterone acts primarily on the epithelial cells of the cortical collecting duct in the kidney. Here, the hormone binds to the intra-cellular mineralocorticoid receptor, and induces conformational activation of the receptor and transcription of a number of genes follows, resulting in increased expression and activity of the basolateral sodium/potassium (Na + /K + ) ATPase and the net effect is increased sodium and water reabsorption and potassium excretion. [2],[3]

Aldosterone production may increase in several pathological conditions including chronic cardiac failure or nephrovascular hypertension. [4] Moreover, administration of loop diuretics may increase aldosterone production as a consequence of the physiological adaptation to the sodium and water wasting, secondary to the inhibition of tubular chloride transport and carbonic anhydrase activity in the proximal tubule. These diuretic actions lead to an overload of sodium and water to the distal tubules, which stimulates the renin-angiotensin-aldosterone system (RAAS). [5]

In children and adults, aldosterone secretion is stimulated primarily by the angiotensin II, which is produced by renin action. Active renin secretion is regulated principally by several interdependent factors: a renal baroreceptor mechanism in the afferent arteriole that senses changes in renal perfusion pressure as well as changes in delivery of sodium chloride to the macula densa cells of the adrenergic receptors. [6]

In the neonatal period, many factors may interfere with aldosterone production, such as gestational age, birth weight, drugs, and degree of illness. [7] Very low birth weight (VLBW), due to premature birth or to intra-uterine growth retardation, adversely affects normal renal development. In addition, exposure to potentially injurious renal stimuli such as long-term administration of furosemide to treat chronic lung/heart disease is associated with increased urinary excretion of aldosterone. [8] Careful attention should be directed to this high-risk group of patients during the perinatal period to avoid and detect early, these complications. [9]

The aim of our study was to assess the urinary aldosterone excretion (UAE) in the first 72 h of life in VLBW infants and to identify some possible clinical and biochemical variables that may influence this parameter.


   Subjects and Methods Top


This hospital based, prospective cohort study was conducted in the Neonatal Intensive Care Unit (NICU) of Pediatric Hospital, El-Minia University. The target population of this study consisted of 30 preterm infants admitted to the NICU, from September 2012 to September 2013 with body weight <1500 g and gestational age ≤32 weeks during the first three days of life. Infants with major congenital anomalies, sepsis, perinatal asphyxia, and intraventricular hemorrhage were excluded from the study. An informed consent was taken from parents before the study. Infants were subjected to detailed medical history, assessment of gestational age and anthropometric measurements. Investigations including urinary aldosterone in the first 72 h (μg/24 h), serum sodium and potassium, complete blood count, C-reactive protein, and blood culture were performed to exclude preterm infants with sepsis.

During the first 72 h of life, urine was collected for 24 h. A plastic urine collection bag was attached to the infant's perineum, and urine was removed from the bag and refrigerated after each void. At the end of each collection, mild supra-pubic pressure was applied to empty the bladder as completely as possible. Loss of urine was evaluated by weighing the diapers after emptying the urine collection bag. Urine collection failure was defined as a urine loss more than 15% of overall 24 h diuresis. Urine collection was stopped if a perineal rash appeared. All samples were stored at 4°C until analysis.

Measurement of urinary aldosterone was made by ELISA manufactured by the Diagnostic Products Corporation (USA), which has intra-and inter-assay coefficients of variation of 4.7% and 5.7%, respectively. The urine aldosterone was expressed in μg/24 h, indicating the overall amount of aldosterone excreted during 24 h diuresis and in pg/mL, indicating the absolute amount of aldosterone excreted.

Plasma sodium, potassium, and chloride were measured by flame photometry at the end of urine collection.

An exploratory analysis was conducted with the Mann-Whitney U-test to assess the association between UAE and dichotomous variables, and with Pearson's correlation coefficient between UAE and continuous variables. Step-wise linear regression analysis was started with all the variables associated with UAE in the initial model; the significance level for addition to the model was set at 0.2 and the significance level for removal from the model was set at 0.3. All variables except plasma sodium and gestational age were dropped in the final model. The final model showed a significant independent association between plasma sodium and UAE [coefficient −0.02, 95% confidence interval, CI (−0.03; −0.004); adjusted R 2 0.33].


   Results Top


Thirty consecutive infants were enrolled in the study. Baseline characteristics of the study population are shown in [Table 1]. The mean postnatal age at which the 24-h urine collection was performed was 44 ± 14 h of life. The mean overall UAE value was 0.176 ± 0.05 μg/24 h and the mean absolute amount of aldosterone excreted in the urine was 1906 ± 271 pg/mL.
Table 1: Baseline characteristics of the study population.

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The exploratory analyses are presented in [Table 2] and [Table 3] and the only categorical variable associated with urinary aldosterone was RDS. Among the continuous variables, birth weight, plasma sodium, and chloride were significantly correlated to UAE. The association of UAE with sex, type of delivery, intraventricular hemorrhage, mechanical ventilation, sepsis and, patent ductus arteriosus was statistically insignificant. A statistically significant positive correlation existed between UAE and birth weight (coefficient 0.567, P = 0.001) [Figure 1] and that infants with RDS had lower urinary aldosterone levels than infants without respiratory distress (P = 0.007) [Figure 2]). Only plasma sodium was a significant independent factor that negatively influenced UAE on linear regression analysis (coefficient −0.768, P <0.001) [Figure 3].
Figure 1: Correlation between UAE (μg/24 h) and weight (in kg) among study population.

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Figure 2: Box-plot for comparison between RDS and non-RDS neonates regarding their UAE (μg/24 h) level.

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Figure 3: Correlation between UAE (μg/24 h) and serum sodium (in mEq) among study population.

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Table 2: Influence of neonatal factors on urinary aldosterone values. Dichotomous variables.

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Table 3: Influence of neonatal factors on urinary aldosterone values. Continuous variables.

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   Discussion Top


Aldosterone, as a part of the RAAS, plays a key role in the homeostatic control of arterial pressure, tissue perfusion, and extracellular volume. Aldosterone production may increase in several pathological conditions such as chronic cardiac failure or nephrovascular hypertension. [10] Moreover, the administration of loop diuretics may increase aldosterone production as a consequence of the physiological adaptation to the sodium and water wasting, secondary to the inhibition of tubular chloride transport and carbonic anhydrase activity in the proximal tubule. These diuretic actions lead to an overload of sodium and water to the distal tubules, which stimulates the RAAS. [11]

While clear reference values for aldosterone exist for pediatric populations, few and heterogeneous data are available for term and pre-term neonates. The studies carried out during the neonatal period varied in the timing of sampling and almost all determined plasma aldosterone level. [12],[13]

This study showed that in VLBW infants, the mean ± standard deviation (SD) overall UAE value during the first 72 h of life was 0.176 ± 0.05 (0.119-0.320) μg/24 h. Urinary aldosterone levels were chosen instead of plasma to avoid blood sampling in tiny babies and, since urinary excretion of aldosterone may be affected by diuresis, we also determined the absolute mean ± (SD) amount of aldosterone excreted in the urine, which was 1906 ± 271 (1432-2433) pg/mL.

Martinerie et al [14] suggested that urinary aldosterone measurement is the best index for accurate evaluation of the mineralo-corticoid effector mechanisms and that plasma aldosterone is not a good parameter at birth. They 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 noninvasive method to investigate aldosterone sensitivity in preterm and full-term infants.

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.

In the present study, the variables significantly associated with UAE in the exploratory analysis were RDS, birth weight, and plasma sodium. Nevertheless, the only variable independently associated with UAE on linear regression analysis was plasma sodium. Indeed, infants with lower plasma sodium had higher UAE. These findings are not in agreement with those of Leslie et al, [15] who found that infants with RDS had levels of UAE similar to those of infants without RDS. On the contrary, we found that infants without RDS had higher urine aldosterone levels than those with RDS. The explanation of this finding may be that patients with RDS often present with an oliguric phase, followed by a spontaneous diuretic phase, typically occurring at 24-72 h that precedes the improvement in lung disease. [16] We hypothesize that during this oliguric phase of the disease, there is an increase in extra-cellular volume with consequent hyponatremia that stimulates aldosterone production.

We found a negative correlation between plasma sodium and UAE during the first three days of life that may confirm the physiological partial aldosterone resistance in human neonates. This is followed by a progressive increase of renal mineralocorticoid receptor expression level in the 1 st days after birth, concurrently with renal maturation. Our data are consistent with those of Shaffer et al [17] and Costa et al [18] who found a negative correlation between plasma sodium levels and plasma aldosterone at seven days of life, but not on the 1 st day of life.

There was a statistically significant positive correlation between UAE and birth weight not independently associated with UAE on linear regression analysis. The influence of birth weight on aldosterone production has been controversial. In fact, Dörr et al [19] found a higher umbilical cord aldosterone level in premature infants than in term infants, whereas Hubl et al [20] showed that umbilical cord aldosterone levels increase with gestational age.

Procianoy and de Oliveira-Filho [21] found a significant positive correlation between birth weight and serum umbilical cord aldosterone levels, while Bourchier [13] found that plasma aldosterone levels were unaffected by gestational age.


   Conclusions Top


RAAS of VLBW infants seems to be able, even immediately after birth, to respond to variations of plasma sodium concentrations, and that measurement of urinary aldosterone levels constitutes an interesting method to determine aldosterone production, avoiding blood sampling in neonates. Moreover, early and longitudinal monitoring of UAE may be useful in some clinical conditions that require chronic diuretic treatment, such as congestive heart failure and bronchopulmonary dysplasia.

The sample size of our study is not large enough to detect the presence of other independent variables that influence the production of aldosterone and further clinical investigations are needed to evaluate aldosterone resistance and the regulation of the RAAS in preterm neonates.


   Acknowledgment Top


We would like to thank all the staff members of NICU and Biochemistry Department at ElMinia Pediatric Hospital for their help during this study.

Conflict of interest: None declared.

 
   References Top

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Simpson SA, Tait JF, Bush IE. Secretion of a salt-retaining hormone by the mammalian adrenal cortex. Lancet 1952;2:226-8.  Back to cited text no. 1
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Costa S, Gallini F, De Carolis MP, et al. Urinary aldosterone excretion and renal function in extremely-low-birth-weight infants following acute furosemide therapy. Neonatology 2009;96:171-4.  Back to cited text no. 4
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Bourchier D. Plasma aldosterone levels in the 1st week of life in infants of less than 30 weeks gestation. Eur J Pediatr 2005;164:141-5.  Back to cited text no. 13
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Martinerie L, Pussard E, Foix-L'Hélias L, et al. Physiological partial aldosterone resistance in human newborns. Pediatr Res 2009;66:323-8.  Back to cited text no. 14
    
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Leslie GI, Gallery ED, Arnold JD, Nicholson E. Hyaline membrane disease and early neonatal aldosterone metabolism in infants of less than 33 weeks gestation. Acta Paediatr Scand 1991;80:628-33.  Back to cited text no. 15
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Costa S, Cota F, Romagnoli C, et al. Early urinary aldosterone excretion in very low birth weight infants. J Renin Angiotensin Aldosterone Syst 2012;5:1-5.  Back to cited text no. 18
    
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Dörr HG, Sippell WG, Versmold HT, Bidlingmaier F, Knorr D. Plasma aldosterone and 11-deoxycortisol in term neonates: a reevaluation. J Clin Endocrinol Metab 1987;65:208-10.  Back to cited text no. 19
    
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Hubl W, Büchner M, Bellée H, Mühlbach F, Dörner G. Study of plasma aldosterone in normal pregnancy, in pre-eclamptic women and in cord plasma of newborns. Endokrinologie 1979;73:162-6.  Back to cited text no. 20
    
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Correspondence Address:
Abdel Hakeem Abdel Mohsen
Department of Pediatrics, Faculty of Medicine, El-Minia University, Cairo
Egypt
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DOI: 10.4103/1319-2442.185234

PMID: 27424689

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    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]

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