Calcium, sodium and potassium urinary excretion during the first five days of life in very preterm infants

BACKGROUND: Hypercalciuria has been associated with the risk of nephrocalcinosis and renal stones in both adults and children. Renal calcifications are frequently encountered in preterm infants because this particular population presents most of the risk factors of increased urinary calcium excretion. Urinary calcium excretion has been shown to correlate with sodium and potassium excretions in adult patients, but these correlations have not been demonstrated in the early neonatal period yet. OBJECTIVE: To define the relationship between calcium urinary excretion and sodium or potassium excretions in the first 5 days of life in preterm babies. METHODS: A prospective study was conducted in 16 preterm infants born before 32 weeks of gestation (body weight 1,373 +/- 310 g; gestational age 29.1 +/- 1.6 weeks). Fifteen consecutive 8-hour urine collections were performed for each infant from the 8th hour of life. A plasma sample was obtained at the end of each urine collection. Sodium, potassium, calcium and creatinine were measured in urine and blood samples as often as possible. RESULTS: (1) Urine sodium excretion was 6.56 +/- 4.35 mmol/kg per day. (2) Urinary calcium excretion was 5.9 +/- 5.4 mg/kg per day and the urinary calcium/creatinine ratio was 0.48 +/- 0.39 mg/mg. (3) Urinary calcium and sodium excretion were positively correlated (r = 0.65, p = 0.0001), while an inverse correlation was found between calcium and potassium excretion (r = 0.31, p = 0.004). CONCLUSION: The mean values of urinary calcium excretion and calcium/creatinine ratio observed in our population were higher than 4 mg/kg per day and 0.4 mg/mg, respectively, i.e. boundary values previously associated with an increased risk of nephrocalcinosis. We hypothesize that an increase in urinary sodium excretion in this population may facilitate calcium excretion.     

Urinary albumin excretion rate and puberty in non-diabetic children and adolescents

Slightly elevated urinary albumin excretion rate (microalbuminuria) is a marker of early diabetic nephropathy, but it is unclear if the established definition of microalbuminuria (20–200 μg/min) is correct for children and adolescents. We investigated the albumin excretion rate, albumin/creatinine ratio and urinary albumin concentration in 150 healthy schoolchildren and adolescents to (a) obtain a reference value for albumin excretion rate, (b) relate albumin excretion to pubertal stages and (c) evaluate albumin/creatinine ratio and morning albumin concentration as screening methods for elevatcd albumin excretion rate. Albumin concentration was measured by immunoturbidimetry in timed overnight urine samples. The albumin excretion showed a skewed distribution (geometric mean 3.2 μg/min, 95 percentile 15.1 μg/min). In girls, a peak in the albumin excretion rate was found at the pubertal stage 4 (Tanner) and in boys at stage 5. Albumin/creatinine ratio of 2.5 mg/mmol as a scrccning level for elevatcd albumin cxcrction (15 μg/min) showed a high positivc (0.88) and negative (0.99) predictive value.     

Renal tubular proteinuria and microalbuminuria in diabetic patients.

The urinary extraction of albumin, retinol binding protein, and N-acetyl-beta-D-glucosaminidase were studied in 60 children with insulin dependent diabetes mellitus and in 45 normal children to find out whether the renal tubules played a part in causing the early increase in urinary excretion of albumin that occurs in diabetes mellitus. Two overnight urine samples were collected and the protein excretion measured and expressed as the geometric mean of the protein to creatinine ratio (urinary albumin:creatinine ratio, urinary retinol binding protein:creatinine ratio, and urinary N-acetyl-beta-D-glucosaminidase:creatinine ratio, respectively). The excretion of all three proteins was significantly higher in the diabetic children with 15 (25%) of urinary albumin:creatinine ratio, 16 (27%) of urinary retinol binding protein:creatinine ratio, and 43 (72%) of urinary N-acetyl-beta-D-glucosaminidase:creatinine ratio values being above the normal range. Significant correlations were observed between urinary albumin:creatinine ratio and urinary retinol binding protein:creatinine ratio, urinary albumin:creatinine ratio and urinary N-acetyl-beta-D-glucosaminidase:creatinine ratio, and urinary retinol binding protein:creatinine ratio and urinary N-acetyl-beta-D-glucosaminidase:creatinine ratio. There were also significant correlations between glycated haemoglobin 1c (HbA1c) and these proteins, especially N-acetyl-beta-D-glucosaminidase. No correlations were observed with the fractional excretion of sodium, flow rate of urine, glomerular filtration rate, or blood pressure. These data show that tubular abnormalities are present early in the course of insulin dependent diabetes mellitus and suggest that the early increase in urinary excretion of albumin may be at least partly tubular in origin, and that glycaemic control may influence this aspect of proximal tubular function.     

Urinary albumin excretion rate and puberty in non-diabetic children and adolescents

Slightly elevated urinary albumin excretion rate (microalbuminuria) is a marker of early diabetic nephropathy, but it is unclear if the established definition of microalbuminuria (20–200 μg/min) is correct for children and adolescents. We investigated the albumin excretion rate, albumin/creatinine ratio and urinary albumin concentration in 150 healthy schoolchildren and adolescents to (a) obtain a reference value for albumin excretion rate, (b) relate albumin excretion to pubertal stages and (c) evaluate albumin/creatinine ratio and morning albumin concentration as screening methods for elevatcd albumin excretion rate. Albumin concentration was measured by immunoturbidimetry in timed overnight urine samples. The albumin excretion showed a skewed distribution (geometric mean 3.2 μg/min, 95 percentile 15.1 μg/min). In girls, a peak in the albumin excretion rate was found at the pubertal stage 4 (Tanner) and in boys at stage 5. Albumin/creatinine ratio of 2.5 mg/mmol as a scrccning level for elevatcd albumin cxcrction (15 μg/min) showed a high positivc (0.88) and negative (0.99) predictive value.     

RENAL FUNCTION AS A MARKER OF HUMAN FETAL MATURATION

Abstract. Sixty clinically well infants of various gestational ages (27 to 40 weeks) were studied from 24–40 hours after birth to evaluate glomerular filtration rate and renal excretion rate of sodium at various stages of fetal maturation. Creatinine clearance was directly related to gestational age ( r =0.643). Fractional sodium excretion was inversely related to gestational age ( r =-0.755). The renal functions of small for gestational age infants were similar to those of full-term infants whose birth weights were appropriate for gestational age. The data showed that the glomerular functions of an infant below 32 weeks of gestation were more predominant than the tubular function resulting in a greater fractional sodium excretion rate and higher urinary Na loss in infants of this gestational age, when compared with the more mature infants.     

围产期早产儿尿蛋白动态变化

目的：研究早产儿肾功能特点及与胎龄、日龄的关系。方法：利用免疫比浊法、速率法及ELISA法,测定28～31周组(Ⅰ组)、32～34周组(Ⅱ组)、35～37周组(Ⅲ组)早产儿生后第1天、第4天、第7天尿微量白蛋白(mAlb)、视黄醇结合蛋白(RBP)、N-乙酰-β-D氨基葡萄糖苷酶(NAG)值。结果：同一胎龄段尿mAlb随着日龄增加有下降趋势,但差异无显著性(P>0.05);同一日龄mAlb随胎龄增加而降低,差异有显著性(P<0.05 或 0.01)。尿RBP,NAG在Ⅰ组和Ⅲ组随日龄增加而增加,在生后第4天形成峰值,而后明显下降,尤以Ⅰ组不同日龄间RBP和NAG差异有显著性(P<0.01 或 0.05)。同一日龄尿RBP,NAG随胎龄增加而明显降低,尤以生后第4天和第7天不同胎龄间RBP和NAG差异有显著性(P<0.05 或 0.01)。结论： 早产儿肾小球、肾小管尚在发育中,受胎龄日龄影响较大。     

Recovery of protein from urine specimens collected in cotton wool.

Cotton wool balls have been used to aid the collection of urine from infants. Concentrations of two urinary proteins, albumin and retinol binding protein, decreased by 40 and 80% respectively within 15 minutes of contact with the cotton wool. Cotton wool balls should not be used when investigating proteinuria.     

Urinary aquaporin-2 excretion in preterm and full-term neonates

The study was undertaken to define the role of aquaporin-2 (AQP2) in renal concentrating performance by measuring urinary AQP2 excretion and urine osmolality in healthy preterm and full-term neonates during early postnatal life. Random urine samples were obtained from 9 full-term newborn infants (mean birth weight 3,218 g, mean gestational age 39.2 weeks) at postnatal ages of 1, 3 and 5 days. Five premature infants with a mean birth weight of 1,570 g and mean gestational age of 30.6 weeks were studied at the end of the 1st week and then weekly up to the 6th week. Urine osmolality (Knauer osmometer), creatinine (modified Jaffé's method) and AQP2 concentrations (radioimmunoassay) were measured. In full-term neonates, urinary AQP2 excretion showed no consistent changes over the age period studied, while urine osmolality decreased significantly with advancing age. In premature infants, urinary AQP2 excretion remained practically unchanged during the first 4 weeks followed by an abrupt increase thereafter. Urine osmolality did not follow the developmental pattern of AQP2 excretion; its mean values varied only from 78 +/- 39 to 174 +/- 146 mosm/l during the experimental period. It is concluded that during the early postnatal period, urinary AQP2 excretion does not serve as a direct marker of the renal action of AVP and the renal capacity to concentrate urine.     

Relationship of urinary anion gap to urinary ammonium excretion in the neonate

The present study was undertaken to define the relationship of urinary anion gap (UAG = sodium plus potassium minus chloride) to urine ammonium concentration in preterm and full-term neonates with spontaneous and NH4Cl-induced metabolic acidosis. Studies were performed in 10 premature infants (mean birth weight: 1,618 g, gestational age: 30.8 weeks) weekly for 6 consecutive weeks, in 11 full-term neonates (mean birth weight: 3,085 g, gestational age: 38.6 weeks) on the 7th day of life and in 25 older control infants (mean age: 6.5 months, body weight: 6,802 g) before and after NH4Cl-loading test. Blood acid-base parameters, plasma electrolyte concentrations, urine pH, ammonium, titratable acidity, bicarbonate, net acid and electrolyte concentrations were measured, UAG calculated. It was demonstrated that the significant reduction in plasma total CO2 content induced by NH4Cl administration and the subsequent elevation in urinary ammonium concentration was associated with some decrease of UAG in each group. In premature infants there was no relationship between urinary ammonium excretion and UAG during the first 2 weeks of life while from the 3rd week onward a significant negative correlation could be demonstrated. In one-week-old full-term neonates UAG also tended to decline with increasing ammonium concentrations; this relationship, however, proved to be insignificant. In the older control infants urinary ammonium excretion was found to correlate negatively to UAG. It is concluded that due to marked dynamic changes in unmeasured ionic composition of neonatal urine UAG is not a valuable index of urinary ammonium excretion in newborn infants during the first weeks of life.     

Normal values for urinary N-acetyl-beta-glucosaminidase excretion in preterm and term babies.

Urinary N-acetyl-beta-glucosaminidase (NAG) excretion was measured in 14 healthy, preterm, male neonates with gestational ages between 32 and 35 weeks. Daily NAG excretion increased significantly during the first four weeks of life. No correlation was observed between urinary NAG:creatinine ratio and postnatal age regardless of whether measurements were taken from the whole 24 hour urine collection or from an isolated urine spot sample at the same time on each day. When the preterm infants were compared with a group of 20 healthy, full term, male infants at a postnatal age of 7 days the NAG:creatinine ratio was significantly higher in the preterm group, the measurements having been taken from single urine spot samples. We suggest that this variable be used in the evaluation of renal tubular integrity during the neonatal period.     

Free Urinary Cortisol Immunoreactive Levels in Premature and Full Term Infants

ABSTRACT. Urinary free immunoreactive Cortisol excretion was measured in 20 full term, 20 premature and 20 premature newborns of mothers who had been treated with 12 mg betamethasone 48 hours before delivery. In 10 full term newborns delivered normally, values were 40 ±20 nmol/mmol creatinine on the first, 23±8 on the second and 21±6 on the third day of life. In 10 full term newborns with stressful delivery, the corresponding values were 63±39, 44±33 and 32±17 nmol/mmol creatinine in the first three days of life. The levels of urinary free immunoreactive Cortisol of 10 premature newborns delivered without stress were 170±116, 91±75 and 70±61 nmol/mmol creatinine respectively, on days one, two and three of life. Ten premature infants with respiratory distress syndrome had values of 471 ± 187, 526±465 and 636±906 nmol/mmol creatinine, respectively. The 10 premature newborns whose mothers had received betamethasone, had urinary free immunoreactive Cortisol levels of 109±120, 55±42 and 66±84 nmol/mmol creatinine, lower than the other premature infants. This difference, however, was not statistically significant. We conclude that premature infants regardless of stress or normal labor have high urinary free immunoreactive Cortisol excretion, suggesting that prematurity per se is a potent stress.     

Urinary excretion of n-acetyl-beta-D-glucosaminidase and retinol binding protein as alternative indicators of nephropathy in patients with type 1 diabetes mellitus

Abstract: Diabetic nephropathy (DN) is usually characterized by glomerular dysfunction, with microalbuminuria as an early indicator. Urinary excretion of smaller molecular weight proteins such as n-acetyl-β-glucosaminidase (β-NAG) and retinol binding protein (RBP) indicate proximal tubular dysfunction, and may identify diabetic patients at risk of developing diabetic nephropathy. In a trial to assess renal tubular function, urinary excretion of β-NAG (by colorimetric assay) and RBP (by ELISA) were determined in 59 type 1 diabetic patients (mean age 15 ± 3.2 yr). Of the 59 patients, 11 were microalbuminuric while 48 had normal urinary albumin excretion (UAE). Patients were compared with 40 matched healthy subjects. Diabetic patients with microalbuminuria (n = 11) had concomitant renal tubular disorder indicated by high urinary β-NAG in all (100%) and RBP in 10 (90.9%) of them. Meanwhile, patients without microalbuminuria (n = 48) had both tubular markers excreted in urine in significantly higher amounts than controls (mean β-NAG = 6.88 vs. 3.76 U/g Cr, p < 0.001; RBP = 386.6 vs. 151.8 µg/dL, p < 0.001). Among those patients, 29 (61%) had raised urinary β-NAG activity, and 39 (82%) had increased loss of RBP in urine. A significant correlation was found between urinary β-NAG and RBP in normoalbuminuric patients (r = 0.66, p < 0.001), as well as between each of the two tubular markers and HbA1c (r = 0.83, p < 0.001). At 30 and 36 months of follow-up, two out of 48 (4.2%) diabetic patients developed persistent microalbuminuria. Both had elevated baseline HbA1C, and urinary β-NAG. In conclusion, proximal tubular dysfunction may occur independent of glomerular alteration. Whether tubular markers precede the development of microalbuminuria needs further study.     

Urinary nitrite excretion after prophylactic intravenous immunoglobulin in premature infants

AIMS: To investigate the correlation between the prophylactic administration of intravenous immunoglobulin (IVIG) to preterm infants and urinary nitrite levels, which can be utilized as an index of endogenous nitric oxide (NO) formation, and to determine if NO formation plays a role in both therapeutic and adverse effects of IVIG. METHODS: 28 healthy preterm infants were included in this prospective study. They had a mean gestational age of 29.4 +/- 2.2 weeks and weight of 1,387 +/- 371 g. Prophylactic IVIG infusion at a dose of 0.5 g/kg/day was administered when they were 3-10 days old. Urine samples of the neonates were obtained for analysis on days 1, 2 and 3 after IVIG administration as well as 1 day before. Urinary nitrite levels obtained in the subjects were normalized for urinary creatinine concentrations. RESULTS: The mean urinary nitrite levels were: 2.77 +/- 1.66 micromol/mmol creatinine before IVIG administration; 4.33 +/- 3.88 micromol/mmol creatinine on the 1st day of IVIG; 3.77 +/- 2.73 micromol/mmol creatinine on the 2nd day, and 3.64 +/- 3.28 micromol/mmol creatinine on the 3rd day. There was a significant increase in urinary nitrite levels between before and after IVIG administration. There was no statistical difference in urinary nitrate levels between days 1, 2 and 3 after IVIG administration. CONCLUSION: We demonstrated that urinary nitrite excretion is significantly elevated in preterm infants after prophylactic IVIG administration and this result suggests that endogenous NO formation may play an important role in both the therapeutic and adverse effects of IVIG.     

Characterization of proteinuria using random urine samples

The urinary albumin to creatinine ratio (Ualb/Ucr) was compared with quantitative albumin excretion in normal subjects and patients with renal disease. Urinary albumin excretion varied from 3.4 to 4,699 mg/m2/day and Ualb/cr from 5.3 to 6,600 micrograms/mg; the correlation was highly significant (r = .979, p less than .001, n = 20). To characterize normal proteinuria using random urine samples, specimens were obtained from 279 healthy subjects (2 months - 62 years). Total protein, albumin and lysozyme were measured in all samples. Glomerular permeability and tubular function were assessed using the random Ualb/Ucr, the urinary albumin to protein ratio (Ualb/Up) and the urinary lysozyme to albumin ratio (Uly/Ualb). Ualb/Ucr was higher in children less than four years although no age-related differences were noted for Ualb/Up or Uly/Ualb. Furthermore, no differences were seen between males and females and normal reference values are provided. The results of this study support the use of Ualb/Ucr as an estimate of urinary albumin excretion and characterizes normal proteinuria using markers of both glomerular and tubular function.     

Sodium homeostasis in term and preterm neonates. I. Renal aspects.

Eighty five 24 hour sodium balance studies and creatinine clearance measurements were performed in 70 infants of gestational age 27-40 weeks and postnatal age 3-68 days. The kidney''s capacity to regulate sodium excretion was a function of conceptional age (the sum of gestational age and postnatal age) and an independent effect of postnatal age was also observed--extrauterine existence increased the maturation of this function. The sodium balance was negative in 100% of infants of less than 30 weeks'' gestation, in 70% at 30-32 weeks, in 46% at 33-35 weeks, and in 0% of greater than 36 weeks, and the incidence of hyponatraemia closely paralleled that of negative sodium balance. Despite a low glomerular filtration rate (GFR) urinary sodium losses were highest in the most immature babies but fractional sodium excretion (FENa) was exponentially related to gestational age. An independent effect of postnatal age could be identified on FENa but not in GFR. These findings indicate that in infants of greater than 33 weeks'' gestation sodium conservation is possible because of a favourable balance between the GFR and tubular sodium reabsorption, but that below this age GFR exceeds the limited tubular sodium reabsorption capacity. The rapid increase in sodium reabsorption in the first few postnatal days seems to be due to maturation of distal tubular function, probably mediated by aldosterone. We suggest that the glomerulotubular imbalance for sodium is a consequence of the immaturity of the tubuloglomerular feedback mechanism, and we estimate that the minimum sodium requirement during the first 2 weeks of extrauterine life is 5 mmol (mEq)/kg/day for infants of less than 30 weeks'' gestation and 4 mmol (mEq)/kg/day for those born between 30 and 35 weeks.     

Neonatal hypercalcemia in preterm infants fed with human milk

Hypercalcemia (serum Ca greater than or equal to 2.83 mmol/l) was detected in 10 premature infants (gestational age: 31-37 weeks and birthweight: 1100-1950 g). All were fed with pooled human breast milk. Urinary Ca excretion was high (greater than 0.200 mmol/kg/24 h) in all but one infant while serum phosphorus (P) concentration and urinary P excretion were low. Serum immunoreactive parathyroid hormone and plasma 25-hydroxyvitamin-D concentrations were normal. A significant positive correlation was found between serum Ca concentration and urinary Ca excretion, and a negative correlation between serum Ca concentration and serum P concentration or urinary P excretion. Hypercalcemia disappeared spontaneously in two patients, was corrected by a humanized milk in three patients and by P supplementation in five patients. These data suggest that neonatal hypercalcemia is related to P depletion induced by human breast milk in premature infants.     

Reference ranges for plasma cystatin C and creatinine measurements in premature infants, neonates, and older children.

AIM: To establish a reference range in the paediatric population for the new glomerular filtration rate (GFR) marker, cystatin C, and to compare it with that of creatinine. METHODS: Cystatin C and creatinine were measured by particle enhanced nephelometric immunoassay (PENIA) and fixed interval Jaff?e methods, respectively, in 291 children aged 1 day to 17 years, including 30 premature infants with gestational ages ranging from 24 to 36 weeks. RESULTS: In the premature infants, concentrations of both cystatin C and creatinine were significantly raised compared with term infants, with cystatin C concentrations being between 1.10 and 2.06 mg/litre and creatinine between 32 and 135 micromol/litre. In premature infants, there was no significant relation between gestational age and cystatin C or creatinine concentration. Creatinine concentrations fell to a nadir at 4 months of age, rising gradually to adult values by about 15-17 years of age, in contrast to cystatin C, which fell to a mean concentration of 0.80 mg/litre by the 1st year of life, and remained constant throughout adulthood up to the age of 50 years. Neither analyte showed any influence of sex. CONCLUSION: The measurement of cystatin C, rather than creatinine, is more practical for monitoring GFR changes in the paediatric population.     

Urinary excretion of prostaglandin E and F 2 alpha in healthy newborn infants and in infants with hyaline membrane disease

Urinary PGE and PGF 2 alpha excretion was estimated in 11 healthy full-term (mean birth weight, 3327 g; mean gestational age, 39.2 weeks). 15 healthy preterm (mean birth weight, 1722 g; mean gestational age, 32.1 weeks) and in 9 preterm infants suffering from hyaline membrane disease (HMD) (mean birth weight: 1454 g, mean gestational age: 31 weeks). Measurements were carried out on the 1st, 3rd and 5th days of life by radioimmunoassay, using Clinical Assays Inc. RIA kits. Urinary PGE excretion on the first day of life was 3.76 +/- 0.41 ng/day, 2.43 +/- 0.65 ng/day and 1.19 +/- 0.27 ng/day for healthy full-term, healthy premature and premature infants with HMD, respectively. The differences were significant at the level of p less than 0.05. With advancing postnatal age urinary PGE excretion markedly increased in each group (p less than 0.05). Urinary PGF 2 alpha excretion on the first day was 10.8 +/- 2.0 ng/day in full-term, 6.6 +/- 2.2 ng/day in healthy premature and 4.35 +/- 1.9 ng/day in premature infants with HMD. Then an inconsistent rise could be observed without statistically significant difference between the individual groups of various postnatal age and between the different groups of the same postnatal age. The decreased renal PGE production is suggested to be involved in the pathomechanism of HMD.     

Renal functional maturation: renal handling of proteins by mature and immature newborns

Renal clearance of creatinine (C_cr), total protein excterion, urinary protein composition and renal clearance of albumin (C_alb) were measured and calculated in male premature and mature infants of gestational age 29–41 weeks and in mature infants 1 and 3 months of age. Total protein excretion decreased slightly but not significantly during maturation. The urinary protein composition changed significantly as the fraction of low molecular weight proteins decreased from 38% at a gestational age of 29–33 weeks to 24% in mature infants aged 3 months, the albumin fraction increased from 39%–46% and the proportion of higher molecular weight proteins increased from 12%–29%, respectively. C_alb decreased from 2.73–0.80 l/min/1.73 m² in the presence of a rise in C_cr, resulting in a significant fall of the ratio C_alb/C_cr from 0.0137 in the youngest prematures to 0.00147 in 3-month-old mature infants.Abbreviations C_cr clearance of craatinine - C_alb clearance of albumin - GA gestational age - GFR glomerular filtration rate - HMW high molecular weight - LMW low molecular weight - A albumin     

Effect of thyroxine administration on renal functions in newborn infants with perinatal asphyxia.

The study was undertaken to assess the influence of thyroxine given to improve respiratory adaptation in asphyxiated neonates on the recovery of compromised renal functions. Two groups of infants with perinatal asphyxia were selected for the study. Group I consisted of 8 infants treated conventionally, while Group II included 7 infants who in addition to standard therapy were administered 50 micrograms thyroxine at admission and repeated 24 hours later. Their respective mean gestational ages were 38.7 weeks (range: 34-42 weeks) and 37.4 weeks (range: 34-41 weeks). The studies were performed on days 1, 7 and 14 and the results compared to those obtained in 13 healthy neonates with the gestational age of 39.2 weeks (range: 38-41 weeks) (Group III). Asphyxiated neonates had significantly higher plasma uric acid, xanthine, hypoxanthine and creatinine levels (p < 0.05), while their GFR proved to be markedly reduced (p < 0.01) when compared to the values of healthy controls. Moreover, there was a significant elevation of urinary excretion of NAGA (p < 0.001), urine osmolality (p < 0.05), PENa, FECa, RFI (p < 0.05) in infants presenting with perinatal asphyxia. Renal tubular responsiveness to aldosterone measured as TTKG was also found to be depressed (p < 0.025). In response to thyroxine therapy renal functional recovery appeared to be accelerated as indicated by the lower plasma creatinine level, lower rate of fractional electrolyte and urinary NAGA excretion and improved reactivity to aldosterone on days 7 and/or 14 as compared to those obtained in neonates presenting with asphyxia but without thyroxine therapy. The results seem to suggest that thyroid hormones may have an important role in the recovery of renal functions in newborn infants suffering from perinatal asphyxia.