Pediatric Nephrology
Pediatr Nephml (1992) 6:205-213 9 IPNA 1992
Invited review
Mechanisms regulating renal sodium excretion during development Jean E. Robillard 1, Francine G. Smith2, Jeffrey L. Segar3, Edward N. Guillery3, and Pedro A. Jose4 1Department of Pediatrics and CardiovascularCenter, Universityof Iowa, IowaCity,IA 52242, USA, 2Department of Obstetrics,Gynecologyand MedicalPhysiology,Universityof Calgary,Alberta, Canada 3Department of Pediatrics, Universityof Iowa, IowaCity,IA 52242,USA 4Department of Pediatrics, GeorgetownUniversity,Washington, D. C., USA ReceivedSeptember 13, 1991and acceptedSeptember18, 1991
Abstract. The present review focuses on the ontogeny of mechanisms involved in renal sodium excretion during renal maturation. The effect of birth on renal excretion of sodium and the role played by the different tubular segments in the regulation of sodium excretion during maturation are discussed. The influence of circulating catecholamines and renal sympathetic irmervation in regulating sodium excretion during renal development is reviewed. The effects of aldosterone, atrial natriuretic factor, and prostaglandins on sodium regulation during renal maturation are discussed. Special emphasis is given to the potential role of glucocorticoids in modulating sodium excretion early in life.
Key words: Newborn - Fetus - Sodium- Atrial natriuretic factor - Catecholamines - Renal nerves - Aldosterone
Introduction During fetal life, the placenta plays a primary role in the long-term regulation of fetal fluid and electrolyte homeostasis, whereas the fetal kidneys help in protecting the fetus during acute changes in fetal vascular volume [1-5]. At birth, the fetus leaves the protected uterine environment and depends only on the kidney to maintain its extracellular fluid (ECF) volume. The mechanisms by which the developing kidney fulfills this role during the transition from fetal to newborn life and during the newborn period are discussed.
Offprint requests to:
J.E. Robillard
Renal regulation of sodium homeostasis during development In contrast to the adult, who excretes less than 1% of filtered sodium, the fraction of filtered sodium excreted (FENa) is high during fetal life [6-8] and decreases as gestation progresses [6, 8]. In the ovine fetus, FENa decreases from 11% at 130 days' gestation to 5% near term (term 145 days) [8]. Similarly, in preterm infants of less than 30 weeks' gestation, FENamay exceed 5% during the first 3 days of life whereas it is only about 0.2% in term newborns [9, 10]. Based on morphological evidence, a functional glomerulotubular imbalance may be partly responsible for the high FENa seen prior to birth [6]. Studies in fetal guinea pigs [6] have shown that, during the early stages of superficial nephron maturation, there is a phase of functional glomerular preponderance followed by a tubular "catchup" phase associated with an increase in proximal tubular length. However, other investigators [11] have suggested that the reabsorpfion of sodium by the fetal kidney is closely related to glomerular filtration rate (GFR) [11-13], suggesting the presence of a functional glomerulotubular balance. Factors such as a large ECF [14], reduced oxygen availability [15], and differences in the distribution of sodium reabsorpfion between proximal and distal portions of the nephron in the immature as opposed to the mature kidney [12] may also contribute to the high urinary sodium excretion (UNaV) by the fetal kidney. It has been postulated that the greater basal excretion of sodium in preterm than in term neonates is secondary to the decreased ability of the distal tubule in premature infants to reabsorb sodium adequately [16]. Whether this distal abnormality depends on an insufficient rise in aldosterone secretion or is due to a limited tubular response to aldosterone stimulation is discussed later in this review. The effect of birth on renal excretion of sodium has been investigated [17-19]. Studies before birth and following cesarean delivery in sheep have shown that postnatal changes in renal excretion of sodium proceed in two phases [17, 19]. In the first phase which occurs within the
206
GFR ml/min
1
olin
Fetus
lh
4h 24h Newborn
UNa,V and FENa,
[] ueq/mi.
50
0
~'[~1~
Fetus
10 [~) lh
4h
24h
renal interstitial hydrostatic pressure (RIHP) response to volume expansion in newborn animals contributes to the blunted natriuresis of the newborn kidney [27]. RIHP, known to play an important role in mediating the increase in sodium excretion during volume expansion in the adult, is unaltered in developing piglets following a volume load, but increased significantly in adult animals [27]. Developmental changes in tubular Na-K-ATPase activity [28, 29], and in the intrinsic properties of tubular basolateral cell membranes [30], may also contribute to the changes in renal sodium handling during maturation.
0
Newborn
Fig. 1. Glomerular filtration rate (GFR), urinary sodium excretion (UNaV),and fractional sodium excretion (FENa) before and after birth in sheep. * P
Pediatr Nephml (1992) 6:205-213 9 IPNA 1992
Invited review
Mechanisms regulating renal sodium excretion during development Jean E. Robillard 1, Francine G. Smith2, Jeffrey L. Segar3, Edward N. Guillery3, and Pedro A. Jose4 1Department of Pediatrics and CardiovascularCenter, Universityof Iowa, IowaCity,IA 52242, USA, 2Department of Obstetrics,Gynecologyand MedicalPhysiology,Universityof Calgary,Alberta, Canada 3Department of Pediatrics, Universityof Iowa, IowaCity,IA 52242,USA 4Department of Pediatrics, GeorgetownUniversity,Washington, D. C., USA ReceivedSeptember 13, 1991and acceptedSeptember18, 1991
Abstract. The present review focuses on the ontogeny of mechanisms involved in renal sodium excretion during renal maturation. The effect of birth on renal excretion of sodium and the role played by the different tubular segments in the regulation of sodium excretion during maturation are discussed. The influence of circulating catecholamines and renal sympathetic irmervation in regulating sodium excretion during renal development is reviewed. The effects of aldosterone, atrial natriuretic factor, and prostaglandins on sodium regulation during renal maturation are discussed. Special emphasis is given to the potential role of glucocorticoids in modulating sodium excretion early in life.
Key words: Newborn - Fetus - Sodium- Atrial natriuretic factor - Catecholamines - Renal nerves - Aldosterone
Introduction During fetal life, the placenta plays a primary role in the long-term regulation of fetal fluid and electrolyte homeostasis, whereas the fetal kidneys help in protecting the fetus during acute changes in fetal vascular volume [1-5]. At birth, the fetus leaves the protected uterine environment and depends only on the kidney to maintain its extracellular fluid (ECF) volume. The mechanisms by which the developing kidney fulfills this role during the transition from fetal to newborn life and during the newborn period are discussed.
Offprint requests to:
J.E. Robillard
Renal regulation of sodium homeostasis during development In contrast to the adult, who excretes less than 1% of filtered sodium, the fraction of filtered sodium excreted (FENa) is high during fetal life [6-8] and decreases as gestation progresses [6, 8]. In the ovine fetus, FENa decreases from 11% at 130 days' gestation to 5% near term (term 145 days) [8]. Similarly, in preterm infants of less than 30 weeks' gestation, FENamay exceed 5% during the first 3 days of life whereas it is only about 0.2% in term newborns [9, 10]. Based on morphological evidence, a functional glomerulotubular imbalance may be partly responsible for the high FENa seen prior to birth [6]. Studies in fetal guinea pigs [6] have shown that, during the early stages of superficial nephron maturation, there is a phase of functional glomerular preponderance followed by a tubular "catchup" phase associated with an increase in proximal tubular length. However, other investigators [11] have suggested that the reabsorpfion of sodium by the fetal kidney is closely related to glomerular filtration rate (GFR) [11-13], suggesting the presence of a functional glomerulotubular balance. Factors such as a large ECF [14], reduced oxygen availability [15], and differences in the distribution of sodium reabsorpfion between proximal and distal portions of the nephron in the immature as opposed to the mature kidney [12] may also contribute to the high urinary sodium excretion (UNaV) by the fetal kidney. It has been postulated that the greater basal excretion of sodium in preterm than in term neonates is secondary to the decreased ability of the distal tubule in premature infants to reabsorb sodium adequately [16]. Whether this distal abnormality depends on an insufficient rise in aldosterone secretion or is due to a limited tubular response to aldosterone stimulation is discussed later in this review. The effect of birth on renal excretion of sodium has been investigated [17-19]. Studies before birth and following cesarean delivery in sheep have shown that postnatal changes in renal excretion of sodium proceed in two phases [17, 19]. In the first phase which occurs within the
206
GFR ml/min
1
olin
Fetus
lh
4h 24h Newborn
UNa,V and FENa,
[] ueq/mi.
50
0
~'[~1~
Fetus
10 [~) lh
4h
24h
renal interstitial hydrostatic pressure (RIHP) response to volume expansion in newborn animals contributes to the blunted natriuresis of the newborn kidney [27]. RIHP, known to play an important role in mediating the increase in sodium excretion during volume expansion in the adult, is unaltered in developing piglets following a volume load, but increased significantly in adult animals [27]. Developmental changes in tubular Na-K-ATPase activity [28, 29], and in the intrinsic properties of tubular basolateral cell membranes [30], may also contribute to the changes in renal sodium handling during maturation.
0
Newborn
Fig. 1. Glomerular filtration rate (GFR), urinary sodium excretion (UNaV),and fractional sodium excretion (FENa) before and after birth in sheep. * P
