Postnatal
Adjustment
in Renal
Function
Jose Strauss,
MD,
Salha
S. Daniel,
PhD,
and
L. Stanley
James,
MD
From the Departments of Anesthesiology and Pediatrics, Columbia University, College
of Physicians & Surgeons, New York
ABSTRACT. Renal function was studied serially in 17
healthy term infants during the hours immediately fol-lowing birth. Of 14 infants delivered vaginally eight re-ceived placental blood transfusion and six did not. The remaining three infants were delivered by cesarean sec-tion and received placental blood transfusion. Results indicate that the general pattern ofchange in urine output (V), clearance of inulin (CIN), and p-aminohippuric acid
(CPAH), was similar in all infants despite a wide range in
each of the functions measured. The pattern showed an initial increase in V, CIN, and CPAH followed by a decline to low values in all infants by 3 hours of age. Urine osmolality and output generally changed in opposite di-rections. During the first hour the values for V ranged from 0.02 to 0.47 ml/min; for CIN, from 0.5 to 9.1 mi/mm; for CPAH, from 1.4 to 21.8 mi/mm; and for osmolality,
from 98 to 457 mOsm/kg. By 4 hours of age the values for V ranged from 0.01 to 0.15 ml/min; for CIN, from 0.8 to
3.7 ml/min; for CPAH, from 0.8 to 7.5 mb/mm; and for
osmolality, from 240 to 520 mOsm/kg. The initial values of V, CIN, and CPAH, as well as the changes, were greatest
in those infants who received a placental transfusion; however, there were no statistical differences among the means of the various groups. By 4 hours of age, the range of values observed in the initial measurement was much less pronounced. This probably reflects the achievement of stability of renal circulation following adaptation to a variety of stresses during the intrapartum period.
Pedi-atrics 68:802-808, 1981; kidney function in newborn, renal function.
A rapid increase in glomerular filtration rate, renal blood flow, and concentrating ability of the kidney during the first weeks of extrauterine life has been reported in the human as well as in several animal ‘ These changes are generally
at-Received for publication Oct 22, 1980; accepted Jan 27, 1981.
Dr Strauss’ present address: Department of Pediatrics,
Univer-sity of Miami School of Medicine, Miami, FL 33124.
Reprint requests to (L.S.J.) Department of Pediatrics, Columbia
University, College of Physicians & Surgeons and Babies Hos-pita.l, 630 W 168th St, New York, NY 10032.
PEDIATRICS (ISSN 0031 4005). Copyright © 1981 by the American Academy of Pediatrics,
tributed to alterations in cardiac output, systemic blood pressure, vascular resistance, and body de-mands during and immediately following birth.7
The immediate postnatal changes in renal func-tions, however, have not been investigated
previ-ousby. Earlier we reported a wide range of values in urine output and clearance rates in healthy infants during the first 3 hours of life with measurements based on single samples.8 In this study various renal functions in the immediate postnatal period were examined serially in order to describe the early adjustment of the kidney to extrauterine life.
MATERIALS
AND
METHODS
A group of 17 healthy term infants born at the Sloane Hospital were studied during the first 4 hours of life. All infants were vigorous with one
minute Apgar scores of 7 or higher; their weights ranged from 2,400 to 4,000 gm. Fourteen infants were delivered vaginally following spontaneous la-bor and three by cesarean section without labor. Of the infants delivered vaginally, eight received a transfusion of placental blood by manual stripping
of the umbilical cord (group 1); the remaining six received minimal or no placental blood transfusion as the cord was clamped immediately (group 2). The three infants delivered by cesarean section also received a transfusion of placental blood by manual
stripping of the cord (group 3).
Details of this procedure have been described in an earlier report of some of the infants in group 1.8
Whenever possible, a blood sample from the doubly clamped umbilical artery was obtained at birth. The urine passed spontaneously during the first few minutes after birth was also collected. Under sterile
collection period. In most instances no urine was obtained in those infants who had voided sponta-neously prior to or during the catheterization
pro-cedure, indicating that the first voiding was
com-plete. After an initial control arterial sample was
withdrawn, inulin (100 mg/kg) and p
-aminohip-puric acid (PAH) (10 mg/kg) were injected
intra-venously. These amounts were calculated to give
plasma levels of >50 mg/100 ml of inubin and >3
mg/100 ml of PAH following an equilibration period
of 30 minutes.
Urine samples were collected at 15-, 30-, or
60-minute intervals depending on the output. An
ar-terial blood sample (2 to 4 ml) was withdrawn at
the midpoint of each urine collection, but no more
than once every half hour, for determination of pH, Pco2,9 packed red cell volume (hematocrit), oxygen
saturation 210 inulin,’ , PAH,’2 and osmolabity
(Fiske osmometer with a micro attachment). Urine
samples were analyzed for inulin, PAH, and
osmo-laity.
Clearances were calculated using the formula: C = (P/U)V, where P is concentration in plasma atmidpoint of urine collection, U is concentration in
urine, and V is urine output.
After catheterization, the infants were wrapped
loosely in warm blankets in order to maintain body
temperature within a range of 37 to 39 C. The
techniques employed for sampling of blood and
collection of urine allowed the studies to proceed
without arousing the infants, most of whom slept
throughout the study. After each blood sample, the
volume of blood removed was replaced with an
equal volume of normal saline. Thus, alterations in glomerular filtration rate or urine output were
mm-imized. 1.3.14
This study was undertaken in the years 1960 to
1963 before written parental consent was required.
The mother’s permission was nevertheless obtained
prior to the studies. All babies were observed care-fully during their stay in the hospital and a
follow-up examination was conducted at 6 months of age. No infection or complication developed in any of
the infants studied.
RESULTS
Clinical and biochemical data of the infants stud-ied are presented in Table 1. At 0.5 hour of age, 13/
17 infants had arterial pH values higher than 7.20. By 5 hours of age all infants were well oxygenated
with arterial pH values of 7.30 or higher. There
were no notable differences in values among infants
in the three groups except for Hct, which was higher
in those who had received placental blood
transfu-sion.
Volume of the first urine passed shortly after
birth in group 1 ranged from 5.6 to 16.0 ml and the
range in osmolality was 100 to 205 mOsm/kg. In groups 2 and 3, urine volume ranged from 3.0 to 12.0 and 10.6 to 20.5 ml, respectively; the cone-sponding values for osmolality were 98 to 457 and 96 to 207 mOsm/kg. Infant 9, in whom osmolabity of the first urine was 457 mOsm/kg, had episodes of bradycardia during labor but was vigorous and showed no evidence of asphyxia at birth.
The maximal and minimal urine output in mdi-vidual infants during the first 3 hours of life, and the corresponding clearances of inulin and PAH (CIN and CPAH) and urine/plasma ratio for
osmolal-ity (U/PosM) are presented in Fig 1. Values were
plotted at the midpoint of each collection period. There was marked variation in urine flow; the high-est rates were generally found in infants in group 3 (cesarean section, transfused) whereas the lowest
values were observed in group 2 (vaginal, not
trans-fused). Despite variation in urine output, all infants showed an increase in urine flow which reached a maximum between 1 and 2 hours of age. The rates then began to fall and by 3 to 4 hours of age, values
less than 0.02 mb/mm were reached. CIN and C1’AH
followed a pattern similar to that observed for urine output, whereas U/POSM changed in the opposite direction. Serial urine output, CIN, CPAH, and UI
POSM for one representative infant from each group
are presented in Fig 2.
The relationship between urine output, CIN, and
CPAH for all infants during maximal and minimal outputs are presented in Figs 3 and 4 without regard to age. There was a positive correlation between V,
CIN, and CPAH, values for CIN and CPAH being
great-est when urine output was high. The relationship
held irrespective of the mode of delivery or whether the infant had received placental transfusion. There was also good correlation between CIN and CPAH;
this can be expressed by the following equation:
CPAH 2.07 CIN + 0.57 (r = .885). This gives a mean
for filtration fraction of 0.48 during the first 3 hours of life. The relationship between V and U/POSM is nonlinear; a good negative correlation was found with log U/POSM (log U/POSM 0.115 1.37 V, r
= .719). The highest U/POSM ratio observed among
these infants was 1.73.
Although infants who received a placental blood transfusion, in general, had higher Hct and V
val-ues, there was no correlation between either
mdi-vidual or maximal Hct and V (r = .011) or maximal postnatal increase (r = .121). Of the four infants whose maximal urine flow rates were <0.1 mb/mm,
three had Hct values >57%. There was a weak correlation between the relative increase in blood volume due to manual or spontaneous placental
TABLE 1. Clinical and Biochemical Data*
In- Birth Apgar 1st and Last Blood Sample
fant Weight Score
No. (gm) Age pH Pco2 502
1st Urine
Hct Age Vol- Osmolality of In- (mm Hg) (%) (%) of In- ume (mOsm/kg)
fant fant (ml)
(mm) (mm)
Group 1 (vaginal delivery with placental transfusion)
1 3,300 7 0 7.11 66.8 39.2 35.2 41 6.2 135
153 7.34 37.0 100 58.6
2 3,025 8 39 7.26 39.1 93.3 50.4 .. . .. . ...
261 7.37 31.9 100 52.3
3 2,950 8 32 7.27 45.0 97.0 56.7 21 9.0 205
227 7.35 34.7 100 60.0
4 3,750 8 25 7.30 38.2 97.0 50.4 15 6.8 108 240 7.30 . . . 100 58.4
5 4,220 8 0 7.23 . . . . .. .. . 17 16.0 129
230 7.37 31.3 100 62.3
6 4,000 9 33 7.24 . . . 89.2 .. . 16 11.4 150
180 7.34 . . . 100 55.2
7 2,500 8 45 7.32 43.2 54.3 40 6.4 100
135 7.37 34.9 . .. 58.7
8 3,040 8 51 7.28 40.2 93.3 56.8 58 5.6 ...
140 7.33 36.4 99.4 ...
Group 2 (vaginal delivery, no placental transfusion)
9 3,600 7 0 7.21 65.8 18.8 54.2 20 12.0 457
246 7.37 34.0 100 49.2
10 2,675 8 0 7.25 59.5 26.3 43.9 8 3.2 111
300 7.36 39.1 99.0 39.9
1 1 3,440 8 0 7.27 49.0 65.0 40.0 0 7.0 98
144 7.39 32.0 100 35.0
12 2,600 9 0 7.18 54 3.0 ...
300 7.36 39.5 100 45.1
13 2,400 7 28 7.25 49.1 54.1 52.0 2 6.8 117
176 7.34 32.2 100 55.8
14 3,250 7 40 7.33 35.9 98.3 44.5
240 7.33 37.9 100 44.0
Group 3 (cesarean section)
15 2,660 9 0 7.15 57.7 20.0 55.8 5 20.5 207
112 7.30 44.2 100 48.1
16 3,350 7 49 7.17 63.0 78.5 50.5 47 142 105
156 7.28 47.8 100 53.6
17 3,100 8 0 7.29 46.5 16.6 45.1 4 10.6 96
225
aAbbreviations used are: Pco2, carbon dioxide pressure; 502, oxygen saturation; Hct,
hematocrit.
In all groups, there was a small but significant decrease in plasma osmolality from 295.6 ± 2.91 (mean ± SE) during the first hour to 288.4 ± 2.39 mOsm/kg during the fourth hour of life (P < .05).
During the first hour the values for V ranged from 0.02 to 0.47 ml/min; for CIN, from 0.5 to 9.1 mb/mm; for CPAH, from 1.4 to 21.8 mI/mm; and for
osmolality, from 98 to 457 mOsm/kg. By 4 hours of age the value for V ranged from 0.01 to 0.15 mb/ mm; for CIN, from 0.8 to 3.7 mb/mm; for CPAH, from 0.8 to 7.5 mb/mm; and for osmolality, from 240 to
520 mOsm/kg (Table 2). The initial values of V,
CIN, and CPAH, as well as the changes, were greatest in those infants who received a placental
transfu-sion; however, there were no statistical differences
among the means of the various groups.
Including the first urine excretion, mean total volume of urine excreted during the first 4 hours of extrauterine life in the healthy newborn was: 30 ml for infants delivered vaginally who received a pla-cental blood transfusion; 19.2 ml for infants who did not receive such a transfusion; and 49.9 ml for infants delivered by cesarean section (without ba-bor) who received a placental blood transfusion (Table 3).
DISCUSSION
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AGE IN MINUTES
Fig 2. Serial V, CIN, CPAH, and U/PoSM in three repre-sentative infants.
V CIN CpAN
(mI/m3n) (mi/mm) (mI/mi
0.6 2 24
60 20 ISO 240 AGE IN MINUTES
Fig 1. Urine output (V), inulin clearance (CIN), p-aminohippuric acid clearance (CIAFI), and urine/plasma ratio for osmolality (U/POSM) during maximal (open symbols) and minimal (solid symbols) urine output in 17 infants. Each line represents one infant: circles, vaginal + placental transfusion; triangles, vaginal without placental transfusion; squares, cesarean section + placental transfusion.
tions in individual values and regardless of type of delivery or amount of blood received from the pla-centa. An initial increase in urine output, CIN, and
CPAH was followed by a decrease to low values in all infants by 3 hours of age; the initial values as well
as the changes were, in general, higher in those
infants who received placental blood transfusion.
-J Urine osmolality and output generally changed in
opposite directions. As a consequence of these post-natal changes in renal functions, the scatter in initial values was much less pronounced by 4 hours,
of age.
Urine voided at or shortly after birth, with one exception, was found to be hypotonic with respect to plasma; this finding is in agreement with that of other investigators.1”5”6 The subsequent urine
pro-‘ duced was more concentrated in the majority of
infants.
Infant 9 whose initial urine was hypertonic had had several episodes of bradycardia during labor
and probably was recovering from acute
hypoxia.’7’8 The urine subsequently produced by
this infant was less concentrated. At the end of three hours, U/POSM was 0.8 or higher in most infants, and in nine, urine was hypertonic with respect to plasma; however, the highest value was only 1.73. These findings confirm the hypothesis that although hypertonic urine can be produced by the neonate, the highest urine osmolality in the healthy infant during the postnatal period is much lower than that achieved by an adult with similar
urine output.’922
Although CPAH underestimates the effective renal
plasma flow (RPF) in the neonate,23 it is unlikely
.E
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0.1 0.2 0.3 0.4 0.5
V (mI/mm)
Fig 3. Relationship between V and CIN during maximal (open symbols) and minimal (solid symbols) urine output
in 17 infants: circles, vaginal + placental transfusion;
triangles, vaginal without placental transfusion; squares,
cesarean section + placental transfusion.
C
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Fig 4. Relationship between V and CPAH during maxi-ma! and minimal urine output in 17 infants: symbols as in
legend to Fig 1.
y: 2.95 +30.4x
r: 0.793
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V (mi/mm)
TABLE 2. Urine Output (V), Inulin Clearance (C,N), p-Aminohippuric Acid Clearance
(CPAH), and Osmolality (OSM) in 17 Infants During First and Fourth Hours of Postnatal Life*
1st Hr 4th Hr
Absolute Per kg Weight Absolute Per kg Weight
V (mi/mm) 0.19
(0.02-0.47)
0.06
(0.01-0.20)
0.10
(0.01-0.15)
0.04
(0.01-0.07)
C,N (ml/min) 3.4
(0.5-9. 1)
1.1 (0.3-3.0)
1.9 (0.8-3.7)
0.8 (0.2-2.2)
CPAH (mI/mm) 8.6
(1.4-21.8)
2.7 (0.6-5.8)
4.5 (0.8-7.5)
1.6 (0.3-3.7)
OSM, (mOsm/kg) 240
(98-457)
. .. 291
(240-520)
...
* Absolute and per kilogram body weight values for mean (and range) are given.
life appears to be the consequence of a parallel increase in RPF and glomerubar filtration rate (GFR) that is not matched by changes in tubular reabsorption of water and electrolytes. The reason for this transient increase in the three variables in all infants is not known. One explanation is that all infants receive a certain amount of placental
trans-fusion during the birth process, thus causing an
2 y:I.41+13.05x
0
r:0.805
expansion of extracellular volume. Another expla-nation is that these changes reflect the sum effect of postnatal adjustments in blood pressure, cardiac output, blood redistribution, and renal vascular re-sistance, which proceed at different rates.22’2425 The postnatal diuresis could also be related to the
proc-ess of recovery from mild birth asphyxia.’7”8
Infants delivered by cesarean section have been
reported to have greater total body water than those delivered vagina.lly.26 This could explain the
high urine output, GFR, and RPF found in this
study in the three infants delivered by cesarean
section. Increased secretion of vasopressin,
cate-chobamines, and other hormones that affect kidney vascular resistance and fluid and electrolyte excre-tion during labor and delivery may contribute to the differences between infants born after sponta-neous labor and those delivered by cesarean
sec-tion.273#{176} Vasopressin and catecholamines,
depend-ing on their levels, can produce either natriuresis or antidiuresis in the fetus and newborn.31’32 However, from this small series of vigorous infants and with-out information on hormone levels, it is impossible
to predict the effect that various degrees of birth
asphyxia, labor, and delivery, as well as the rate of recovery of an infant, will have on the pattern of postnatal change in renal function.
The correlation between individual values as well
as the parallel change in the neonate’s urine output,
RPF, and GFR observed in this study have abso been reported by others in older infants. 13,2,33 The decrease in urine output that was present by age 3
hours and was unaccompanied by a decrease in
RPF or GFR seems mainly to be due to increased water reabsorption. The batter is probably due to a gradual increase in tonicity of the medullary
inter-stitium as a result of accumulation of urea and
other waste products that are no longer removed by
the placenta.6”6
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> (3 0 a S C 3)! >: .33 0 S C 3) 6 0increase in Hct. Acute or prolonged hypoxia can
also bead to such an increase (reference 34 and L. S. James and S. S. Daniel, unpublished data, 1965). In addition, increase in blood viscosity due to higher Hct values can cause reduction in RPF that can more than offset the rise due to an increase in blood vobume.u36
In conclusion, these results indicate that regard-less of mode of delivery, postnatal changes in var-ious renal functions are predictable. Although the individual values could not be explained by differ-ences in blood pressure or acid-base status of the infant, stabilization of renal function follows a gen-eral pattern that is similar to the pattern observed in acid-base indices after delivery.’7 The narrowing of the range of renal function by four hours from the initial values observed probably reflects the achievement of stability of renal circulation follow-ing adaptation to a variety of stresses during the perinatal period. It is suggested that the changes in renal function in the immediate postnatal period are not merely the passive reflection of existing unsteady conditions but also represent an active process in the maintenance of homeostasis.
ACKNOWLEDGMENTS
This work was supported in part by US Public Health Service grant IRO 1 HD12737 and National Foundation grant 1-339.
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Tubes and wires,
plugs and poles. They stick the needles into holes.
The medicine
runs in and out,
flowing round and round about.
This tangled mass of my i.v.
Scares the heart right
out of me!
(but I really know that
all it does is help me kill the germs there was!)
