Renal function and renal failure in the newborn

Renal function in the newborn infant varies with conceptual age and should be evaluated in this context. Very preterm infants less than 34 weeks' conceptual age have reduced GFR and tubular immaturity in the handling of filtered solutes when compared to term infants. Premature infants between 34 and 37 weeks' conceptual age undergo rapid maturation of renal function similar to term infants, with establishment of glomerulotubular balance early in the postnatal period. ARF in neonates differs from that seen in older children and adults in that ischemic (e.g., hypoxic) insults and congenital malformations constitute the major pathophysiologic mechanisms responsible for clinically observed oliguria and azotemia. Principles of conservative management are similar to those used in older children except for the greatly increased insensible water loss requirements of the very preterm and premature infant. Technical advances have added peritoneal dialysis and CAVH to the therapeutic regimen for persistent ARF or life-threatening complications of reduced renal function.     

Nitrogen sources for parenteral nutrition in the newborn infant

Protein requirements for the preterm and term infant have been determined by a variety of methods. The parenteral protein needs of the very low birth weight infant are around 3 gm/kg/day and of the term infant approximately 2.2 gm/kg/day for maintenance of normal growth. These values are averages and may need to be modified for individuals depending upon a variety of potentially complicating factors. In this regard, many neonatologists recommend the provision of a maximum of 2 to 2.5 gm/kg/day of protein to newborns under most clinical situations. Whereas excessive administration of protein may result in adverse consequences, the tolerance of young infants to infusion of amino acid solutions is not well defined. Based upon animal studies of fetal amino acid utilization, the preterm infant may be capable of appropriately modifying its supply of amino acids over a relatively broad concentration range. It would appear that the supply of individual amino acids is adequately met by a number of amino acid solutions. The newer preparations appear to be more ideally suited to the special needs of the very low birth weight.     

Glucose transport and system A activity in syncytiotrophoblast microvillous and basal plasma membranes in intrauterine growth restriction

The mechanisms underlying the reduced fetal plasma concentrations of amino acids and glucose associated with intrauterine growth restriction (IUGR) remain to be fully established. The activity of the amino acid transporter system A has been shown to be reduced in the syncytiotrophoblast microvillous membrane (MVM) in IUGR, however the impact of these changes on transplacental transport is difficult to assess without information on system A activity in the basal plasma membrane (BM). In this study we measured system A activity and mediated D-glucose uptake using radiolabelled substrates and rapid filtration techniques, and glucose transporter isoform 1 (GLUT 1) protein expression using Western blots in MVM and BM isolated from human placentas. In term IUGR (n=11) MVM system A activity was unaltered compared to controls (n=9). In contrast, system A activity in MVM was reduced by 50 per cent (P< 0.05) in preterm IUGR (n=8, gestational age 28-36 weeks) as compared to controls (n=8, gestational age 28-35 weeks). BM system A activity was unaltered in both IUGR groups. Similarly, MVM and BM GLUT 1 expression and mediated D-glucose uptake was not affected by IUGR. In all preterm IUGR pregnancies signs of severe fetal compromise were present whereas term IUGR fetuses were less affected. These data support the view that MVM system A activity is related to the severity of compromise in IUGR. The markedly reduced system A activity in MVM in preterm IUGR together with the unaltered activity in BM is consistent with a decreased transplacental transport of neutral amino acids in this pregnancy complication. The hypoglycemia present in utero in some IUGR fetuses is not caused by a decreased glucose transport capacity across the syncytiotrophoblast plasma membranes.     

Follow-up of prematurely born infants

Long-term developmental outcome of the prematurely born is generally related to birth weight as a reflection of gestational age: The more immature the infant, the greater the risk of abnormal developmental outcome. Due to improvements in fetal and neonatal care over the past 25 years, developmental outcome of the preterm group has steadily improved, now approaching the expected outcome for term neonates for those born weighing over 1,000 g. For the group of very immature infants (birth weight less than 1,000 g) abnormal developmental outcome remains a significant risk. For any individual preterm infant, long-term developmental outcome is generally related to the severity and duration of initial illness and the postdischarge environment. Specific causation of developmental abnormality in a particular infant is usually speculative. The overall improvement in the long-term outcome for preterm infants has been gained at great cost in medical resources and is accompanied by emotional costs to families that remain unmeasured. The key to further reducing the risk of abnormal developmental outcome remains the prevention of prematurity. Until that can be accomplished, continued meticulous attention to all the details of superb fetal and neonatal intensive care must be exercised to minimize the risk of handicap in this vulnerable group of patients.     

Salbutamol infusion to treat neonatal hyperkalaemia.

Salbutamol infusion, 4 micrograms/kg in 5 ml of water infused for 20 minutes, was given to treat hyperkalaemia (potassium level > 6.0 mmol/l) in 10 critically ill preterm infants (median gestational age 26 weeks). Seven infants had acute renal failure, two had persistent metabolic acidosis without renal failure and the remaining infant had a combination of acute renal failure and persistent metabolic acidosis. No infant developed a tachycardia or became hyperglycaemic in response to the infusion. Seven of the 10 infants ultimately died but this was at a mean of 9 days following the infusion and as a consequence of complications due to their extreme prematurity or major congenital abnormality. In response to the infusion the potassium level fell in 7 infants with acute renal failure by a median of 1.1 mmol/l (range 0.7-1.8) at one hour but in the three infants with a persistent metabolic acidosis, the potassium level continued to rise. We conclude that salbutamol infusion achieves, without side-effects, at least a temporary reduction in hyperkalaemia in preterm infants with renal failure, but not metabolic acidosis. Its effect is of sufficient duration to allow ample time for definitive therapy to be instituted and thus may be a useful alternative for infants in whom the possible hypoglycaemic side-effects of glucose and insulin should be avoided.     

Renal excretion of citrate in patients with chronic renal failure or nephrolithiasis.

Using a specific citrate lyase method, renal excretion of citrate was studied in 32 normal Chinese males, 30 nondialysed uremic male patients and 35 male subjects who had a history of nephrolithiasis. Patients with uremia or nephrolithiasis were found to have a lower urinary citrate excretion. Tubular reabsorption of citrate was markedly decreased in uremic patients, but in stone patients, the increased renal tubular reabsorption of citrate was only found in patients with hypocitraturia, whose renal citrate excretion was below 650 mumol/day and whose urinary magnesium was also low. Hypocitraturia was found in 45% (16/35) of the patients with renal stones whether their filtered load of citrate was normal or subnormal. Urinary citrate excretion was correlated with renal creatinine clearance in both normal subjects and in patients with renal stones or chronic renal failure. However, urinary phosphate correlating with urinary citrate was only found in normal subjects and in patients with kidney stones. In normal subjects, we found a positive correlation between urinary citrate and phosphate, but in stone patients, we found a negative correlation. Hypercalciuria and hyperoxalaturia were noted in some stone formers, who had, moreover, a lower urinary citrate and ascorbate excretion level. Mean urinary ascorbate excretion in patients with renal stones was markedly below that in normal subjects. Thus, we suggest that low urinary citrate excretion may be prevalent in patients with renal stones or chronic renal failure, and that hypocitraturia can be found in some stone formers, whose tubular reabsorption of citrate may be increased.     

Côlon hyperéchogène et cystinurie. Intérêt du diagnostic prénatal

Cystinuria, an inherited autosomal recessive metabolic disorder, is characterized by the inadequate reabsorption of dibasic amino acids in the proximal convoluted tubules during the filtering process in the kidneys. Homozygous patients make cystine stones, and in the long term this causes renal failure. In the service of gynecology-obstetrics of the hospital of The Conception and in the antenatal diagnostic centre of the hospital of Timone, we observed a patient whose fetus showed a hyperechogenic colon during the third term obstetric ultrasonography. The genetic investigation confirmed the diagnosis of cystinuria in the fetus and in other siblings. A premature diagnosis of cystinuria can therefore prevent the complications of cystinuria by applying simple remedies like hyperhydration and alkalization.     

Development of fetal and neonatal renal function

The development of renal function in the human is an amazingly intricate and complex process. In the vast majority of preterm and term babies, renal development and function are adequate to meet the homeostatic needs of the rapidly growing infant. However, when normal renal development does not occur the effects can be devastating. Pioneering work in the assessment and treatment of fetal renal anomalies has been carried out, but it appears that further studies will be necessary to demonstrate whether widespread applicability of this technology is indicated.     

Cytokine expression in response to bacterial antigens in preterm and term infant cord blood monocytes

BACKGROUND: Neonatal susceptibility to bacterial infection is associated with an immature immune system, but the role of different bacterial antigens in specific responses is largely unknown. OBJECTIVE: To evaluate differences in intracellular cytokine response to physiologically relevant bacterial antigens in term and preterm infants as compared with adults. METHODS: Cord blood samples from preterm and term neonates and adult peripheral blood samples were cultured ex vivo with and without whole heat-killed bacteria. Intracellular leukocyte production of interleukin (IL)-6, IL-10, IL-12, and IL-8 responses was assessed by flow cytometry. RESULTS: Monocytes were the primary producers of all mediators. Escherichia coli was the most potent stimulant. Lactobacillus plantarum 299v activated fewer monocytes as compared with E. coli for all responses (p < 0.05), except for IL-12 in term neonates. IL-6 response to Staphylococcus epidermidis was lower in both groups of neonates as compared with adults (p = 0.023 and p = 0.001). IL-8 response to S. epidermidis was lower in term as compared with preterm neonates and adults (p = 0.003). IL-10 response to group B streptococci was lower in term neonates as compared with adults and higher in preterm as compared with term neonates (p = 0.015). CONCLUSIONS: Monocytes from term neonates compared to preterm neonates show a downregulated anti-inflammatory response to specific bacteria. High neonatal response to pathogenic E. coli in the preterm infant could cause uncontrolled inflammatory response, while lower IL-6 response to S. epidermidis in neonates may indicate a basis for vulnerability to S. epidermidis infection.     

Potassium regulation and progesterone-aldosterone interrelationships in human pregnancy: a prospective study

Little is known about the intrinsic renal and hormonal regulation of potassium excretion in pregnancy despite major alterations in many of the potassium regulatory factors. Forty primigravid women on an unrestricted diet were studied during the second and third trimesters and exhibited constant absolute and fractional potassium excretion despite a significant increase in plasma aldosterone concentration between these stages. The plasma progesterone level rose significantly between studies but closer analysis showed no correlation between individual changes in plasma aldosterone concentration and progesterone between trimesters. In the 14 subjects studied post partum, baseline absolute potassium excretion was not significantly altered but filtered potassium fell and fractional potassium excretion tended to rise. After dietary sodium manipulation at these stages, absolute potassium excretion, fractional potassium excretion, and progesterone were unaltered despite significant changes in plasma aldosterone concentration and sodium excretion. These results suggest that potassium excretion is held constant throughout pregnancy and that renal tubular potassium reabsorption adjusts appropriately to the increased filtered potassium load. Progesterone does not appear to be involved in the acute regulation of potassium or sodium excretion but may have effects on sodium and potassium excretion that are constant, proportional to its placental production, and unresponsive to endogenous changes in mineralocorticoid production.     

Sucking patterns of neonates during bottle feeding: comparison of different nipple units.

The present study was designed to compare the sucking pattern of term and preterm infants during bottle feeding with different types of nipple units (Enfamil single-hole nipple units for term and preterm infants and SMA Nuk nipple units). In addition, the sucking pattern of term neonates during a feeding regimen commonly used in many feeding studies was evaluated (reservoir nipple system). In this system milk flows from a reservoir through a tube and depends on the sucking pressure generated by the infant. Only the Enfamil single-hole nipple units for term and preterm infants were compared in preterm infants. No significant difference in sucking frequency was observed in term neonates with different types of nipple units. Although the mean sucking pressures generated tended to be less among nipple units with higher flow, these differences were not statistically significant. Similarly, no significant difference in total sucking or feeding time was observed among the three nipple units tested. Sucking pressures generated by term infants were significantly less when milk flow was increased markedly utilizing the reservoir system. In preterm infants no differences in sucking frequency, sucking pressure, mean flow, or total feeding time were observed when sucking patterns with term and preterm nipple units were compared. Implications of these findings in feeding neonates are discussed.     

Proximal renal tubular acidosis in pregnancy. A case report and literature review

Renal tubular acidosis is usually associated with chronic renal conditions and is rarely encountered in pregnancy. It may be inherited causing osteomalacia and rickets in children or acquired following autoimmune diseases or following exposure to nephrotoxic agents. It is known to worsen during pregnancy and if left untreated may cause maternal and foetal morbidity or death. We report a 28-year-old woman, gravida 3 para 2, who presented at 30 weeks gestation with lethargy, weakness and generalized myalgia. Investigation revealed severe hypokalaemia and a systemic metabolic acidosis due to proximal renal tubular acidosis. Her previous pregnancies were both complicated by foetal losses at term. Following prompt correction of her electrolyte disturbance and metabolic acidosis, she went on to deliver a healthy female infant at term. Regular evaluation up to 1 year post-partum revealed mild persistence of her hypokalaemia. At 1 year, the infant showed no signs of the disorder and is growing normally.     

Urinary beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase (NAG) as early markers of renal tubular dysfunction in sick neonates.

Urinary beta 2-microglobulin, creatinine, N-acetyl-beta-D-glucosaminidase (NAG), sodium, potassium and plasma beta 2-microglobulin, and creatinine were measured in 34 healthy neonates (including 15 term, 12 prematures with a birth weight between 1.5 and 2.5 kg, 7 prematures with a birth weight less than 1.5 kg), 29 sick neonates (including 6 term, 10 prematures with a birth weight between 1.5 and 2.5 kg, 13 prematures with a birth weight less than 1.5 kg), and 13 term neonates born with meconium-stained amniotic fluid at 1, 3, and 5 days of age. Our data revealed that urinary beta 2-microglobulin, NAG, NAG index (NAG/creatinine), and the sodium concentration were significantly higher in sick preterm and term neonates than in healthy neonates (p less than 0.05). Urinary concentrations of beta 2-microglobulin and NAG were also higher in neonates born with meconium-stained amniotic fluid than in healthy neonates. We conclude that sick neonates have a higher incidence of acute tubular injury. The elevated levels of urinary beta 2-microglobulin and NAG in neonates born with meconium-stained amniotic fluid indicate the existence of tubular dysfunction, probably due to perinatal distress.     

Intrapartum colonization with <Emphasis Type="Italic">Streptococcus pneumoniae</Emphasis>, early-onset sepsis and deficient specific neonatal immune responses

Background  

Intrapartum colonization with Streptococcus pneumoniae (S. pneumoniae) is a rare but important risk factor for severe courses of early-onset sepsis (EOS) in the newborn, as underlined in the case of a preterm infant born after 32 weeks of gestation described here. One potential explanation could be an immature immune response of the neonate to S. pneumoniae, however, immunological data in term and preterm infants are scarce.     

Transient renal tubular acidosis in pregnancy

Renal tubular acidosis in pregnancy is a very rare disorder. Most cases are either inherited or secondary to maternal disease or ingestion of toxic chemicals. We report a 22-year-old woman, previously healthy, who presented at 27 weeks of gestation with preterm labor. Investigation revealed renal tubular acidosis with no obvious etiology. Labor was stopped with various tocolytic drugs and her electrolyte imbalance was corrected. She was delivered at 36 weeks, by cesarean for a nonreassuring fetal heart tracing, of an appropriate-for-gestational-age infant weighing 2905 g. Evaluation 3 and 6 months postpartum revealed gradual, but complete resolution of the acidosis and electrolyte abnormality. The infant is now 7 months old, is growing normally with normal electrolytes, and with no evidence of acidosis.     

Apgar scores and umbilical arterial pH in preterm newborn infants

One- and five-minute Apgar scores and umbilical cord arterial pH values were compared in preterm newborn infants of various gestational ages. The more premature the infant, the more likely the Apgar score was low in the presence of a pH greater than or equal to 7.25. Conversely, the closer to term, the more frequently an infant with a pH of less than 7.25 had an Apgar score of greater than or equal to 7. Therefore, in preterm infants, there is little congruity between the Apgar score and umbilical cord pH. Based on these findings, it is not appropriate to label preterm newborn infants as asphyxiated based on a low Apgar score.     

Behavioral and psychophysiologic assessment of the preterm infant

Cardiorespiratory activity was recorded during attentional responsivity on the Brazelton scale in term and preterm infants. Preterm infants showed less heart rate deceleration, less heart rate variance and less power in the ECG spectrum at frequencies associated with respiratory sinus arrhythmia and oscillations in blood pressure: A lower threshold for attentional stimulation in the preterm infant may trigger a CNS mechanism that protects the infant from stimulus overload. Study of the coordination between behavioral and physiological reactivity provides an understanding of the role of the CNS in mediating information processing.     

Comparative study of parenteral nutrition in renal failure using essential and nonessential amino acid containing solutions

One of the controversies in the nutritional therapy of patients with renal failure is the respective role of either the essential amino acids alone or both essential and nonessential amino acids in the treatment of these patients. During a period when essential amino acids were unavailable, a large number of patients with acute renal failure was treated with a modified solution consisting of both essential and nonessential amino acids. The solution consisted of 3.8 grams of nitrogen in 46 per cent dextrose in units of 750 milliliters. A mean of 2,322 +/- 151 calories was administered to this group of patients. Over-all, the survival rate was 9 per cent as opposed to 75 per cent in the previous group treated with essential amino acids only and hypertonic dextrose, 40 per cent, in the group of historical controls treated with hypertonic dextrose. The groups are not strictly comparable because the group treated with both essential and nonessential amino acids may not have been strictly comparable, particularly with a slightly longer duration of renal failure, higher initial blood urea nitrogen level and lower urine volume than either of the other two groups previously treated. While adequate stabilization, but not a decrease in the blood urea nitrogen level, may be achieved from the use of both essential and nonessential amino acids, the excessive mortality seen may be related to differential effects of essential amino acids in supporting host resistance, while nonessential amino acids do not. The results of this study suggest that, until the safety and efficacy of a mixture of essential and nonessential amino acids in renal failure can be demonstrated, essential amino acids remain the treatment of choice as the nutritional support of patients with acute tubular necrosis.     

Delayed cord clamping

Timing of cord clamping is believed to greatly affect placental transfusion rate and therefore neonatal and infant circulation. Delayed cord clamping of 30–60 seconds after birth, in combination with neonatal position at the level of placenta, respirations and uterine contractility increase haemoglobin and lower iron deficiency rate in both term and preterm infants. In preterm neonates, there is evidence on increased cardiovascular stability and a possible reduction of intraventricular haemorrhage and necrotising enterocolitis as well as need of blood transfusion. Adverse neonatal effects include increase of jaundice requiring phototherapy, without any adverse maternal effects reported, such as postpartum haemorrhage or anaemia. A possible adverse effect is the reduction of total nucleated cells during umbilical cord blood collection. Long term neurodevelopment has been assessed in term neonates, and a possible improvement of fine-motor and social domains in four years of life has been reported. Cord milking is an alternative technique to delayed cord clamping and as studies show, infant outcomes are at least comparable to delayed clamping. Delayed cord clamping of 30–60 seconds is therefore recommended, in both term and preterm neonates, provided there are no contra-indications and phototherapy facilities are available.     

Leukemoid reaction in extremely immature preterm infants

Extremely immature preterm infants rarely present with a leukocytosis exceeding 30,000/microL. The pathogenetic sequence leading to leukemoid reactions in non-malignant diseases remains to be elucidated. Potential triggers for leukemoid reactions in premature infants include prenatal corticosteroids, chorioamnionitis and funisitis or systemic infection. In the two-year period from 2006 to 2007 all infants with a gestational age of less than 26 weeks were screened for leukocytosis. Among our cases, one preterm infant presented with a leukocyte count of 229,300/microL at the age of 48 hours, lasting throughout the first three weeks of life. Impairment of microcirculation and resulting organ dysfunction were not observed. Thus, invasive therapeutic procedures, which are routinely initiated in hyperleukocytosis in accompanying malignant diseases, may not have the same significance in extremely immature preterm infants and should be executed in these patients on an individual basis and with extreme caution.