Renal function in the preterm neonate and the newborn rabbit

Nephrogenesis in the human being proceeds until the 35th week of gestation. The anatomic immaturity of the kidneys in preterm neonates concurs with a functional immaturity on glomerular as well as on tubular level. The studies in this thesis are performed in order to analyse the effect of extrarenal influences on renal function in the developing kidney. Studies are in part performed in newborn rabbits before the end of nephrogenesis, and in part in preterm human neonate

Once-daily versus twice-daily administration of ceftazidime in the preterm infant

Ceftazidime pharmacokinetics in 28 preterm infants (gestational ages, 25.6 to 31.9 weeks) were studied on day 3 of life. Patients with suspected septicemia were randomized on day 1 of life in two groups. One group (n = 13) was administered 25 mg of ceftazidime per kg of body weight once daily, and the other (n = 15) was given 25 mg of ceftazidime per kg twice daily. Both groups also received 25 mg of amoxicillin per kg twice daily. Blood samples were collected on day 3 of life with an arterial catheter at 0, 0.5, 1, 2, 4, 8, and 12 h after an intravenous bolus injection. An additional blood sample was taken at 24 h from the group dosed once a day. High-performance liquid chromatography was used to determine serum ceftazidime concentrations. The pharmacokinetics of ceftazidime were best described by using a one-compartment model. The half-life for the elimination of the drug from serum, apparent volume of distribution, total body clearance of ceftazidime, and inulin clearance were not significantly different for both groups. The ceftazidime/inulin clearance ratio was 0.72 for both groups. However, trough concentrations in serum for the twice-daily group were significantly (P < 0.001) higher (42.0 +/- 13.4 mg/liter) than those for the once-daily group (13.1 +/- 4.7 mg/liter). The latter concentrations were all still substantially higher than the MIC of ceftazidime for major neonatal pathogens. We conclude that the currently recommended dosage of 25 mg of ceftazidime per kg twice daily for preterm infants with gestational ages below 32 weeks may be adjusted during the first days of life to one daily dose at 25 mg/kg, provided that for the empirical treatment of septicemia, amoxicillin at 25 mg/kg is also given twice daily

Beam-induced Fe nanopillars as tunable domain-wall pinning sites

Focused-electron-beam-induced deposition (FEBID) is employed to create freestanding magnetic nanostructures. By growing Fe nanopillars on top of a perpendicular magnetic domain wall (DW) conduit, pinning of the DWs is observed due to the stray fields emanating from the nanopillar. Furthermore, a different DW pinning behavior is observed between the up and down magnetic states of the pillar, allowing to deduce the switching fields of the pillar in a novel way. The implications of these results are two-fold: not only can 3-dimensional nano-objects be used to control DW motion in applications, it is also proposed that DW motion is a unique tool to probe the magnetic properties of nano-objects

Genetic variants associated with adult blood pressure and kidney function do not affect fetal kidney volume. The Generation R Study

Background: Smaller kidneys with reduced number of nephrons in early life lead to impaired kidney function and risk for hypertension and chronic kidney disease. These associations might be partly explained by common genetic variation. Aims: To assess the associations between common genetic variants, which have recently shown to be associated with blood pressure or kidney function, with fetal kidney volume. Study design: A prospective population based cohort study in Rotterdam, The Netherlands. Subjects: 855 children, followed from early fetal life onwards (born 2003-2005). Predictor: Common genetic variants previously associated with blood pressure or kidney function. Outcome measures: Combined third trimester fetal kidney volume. Results: After taking into account multiple testing, only rs12940887 (near ZNF652) was significantly associated with fetal kidney volume (β: 0.88 (95% CI: 0.40; 1.37) cm 3 per minor allele, P-value<0.001), but the effect showed the opposite direction as expected. The remaining common genetic variants were not associated with fetal kidney volume. We also did not find associations of genetic variants previously shown to affect newborn kidney volume, with third trimester fetal kidney volume. Conclusions: Our results suggest that common genetic variants, associated with kidney function or disease and blood pressure, do not affect the third trimester fetal kidney volume. Further studies are needed to elucidate the mechanisms underlying the associations between small kidney size and increased risks of hypertension and impaired kidney function in adulthood

Gender differences in respiratory symptoms in 19-year-old adults born preterm

Objective: To study the prevalence of respiratory and atopic symptoms in (young) adults born prematurely, differences between those who did and did not develop Bronchopulmonary Disease (BPD) at neonatal age and differences in respiratory health between males and females. Methods: Design: Prospective cohort study. Setting: Nation wide follow-up study, the Netherlands. Participants: 690 adults (19 year old) born with a gestational age below 32 completed weeks and/or with a birth weight less than 1500g. Controls were Dutch participants of the European Community Respiratory Health Survey (ECRHS). Main outcome measures: Presence of wheeze, shortness of breath, asthma, hay fever and eczema using the ECRHS-questionnaire

Diuretics in pediatrics: Current knowledge and future prospects

This review summarizes current knowledge on the pharmacology, pharmacokinetics, pharmacodynamics, and clinical application of the most commonly used diuretics in children. Diuretics are frequently prescribed drugs in children. Their main indication is to reduce fluid overload in acute and chronic disease states such as congestive heart failure and renal failure. As with most drugs used in children, optimal dosing schedules are largely unknown and empirical. This is undesirable as it can potentially result in either under- or over-treatment with the possibility of unwanted effects. The pharmacokinetics of diuretics vary in the different pediatric age groups as well as in different disease states. To exert their action, all diuretics, except spironolactone, have to reach the tubular lumen by glomerular filtration and/or proximal tubular secretion. Therefore, renal maturation and function influence drug delivery and consequently pharmacodynamics. Currently advised doses for diuretics are largely based on adult pharmacokinetic and pharmacodynamic studies. Therefore, additional pharmacokinetic and pharmacodynamic studies for the different pediatric age groups are necessary to develop dosing regimens based on pharmacokinetic and pharmacodynamic models for all routes of administration

Ceftazidime pharmacokinetics in preterm infants: Effects of renal function and gestational age

Objective: The objectives of this study were (1) to determine the effects of gestational age on ceftazidime pharmacokinetics in the preterm infant, (2) to relate these effects to changes in glomerular filtration rate (GFR), and (3) to establish appropriate dosage recommendations for preterm infants on day 3 of life. Methods: Multiple-dose pharmacokinetics of ceftazidime (administered twice daily in a 25 or 50 mg/kg body weight intravenous dose) were evaluated in 136 preterm infants on day 3 of life. Blood samples were collected from an arterial catheter 0, 1/2 , 1, 2, 4, 8, and 12 hours after the intravenous dose. An HPLC method was used to determine ceftazidime concentrations in serum. The GPR was studied simultaneously by means of the 24-hour continuous inulin infusion technique. Results: The total body clearance, volume of distribution, and elimination serum half-life of ceftazidime (mean ± SD) were 55,7 ± 34.4 ml/hr (37.3 ± 11.9 ml/hr/kg), 496 ± 228 ml (350 ± 96 ml/kg), and 6.95 ± 2.32 hours, respectively. The mean ± SD peak and trough levels were 114.9 ± 39.4 and 33.9 ± 17.8 mg/L. All infants had a serum trough level above 5 mg/L, Clearance and volume of distribution of ceftazidime and GFR increased significantly with increasing gestational age, whereas serum trough levels and serum half-life of ceftazidime decreased significantly with increasing gestational age. Ceftazidime clearance increased significantly with increasing GFR. Prenatal exposure to indomethacin resulted in significantly lower GFR values and ceftazidime clearances. Conclusions: Dosage recommendations for ceftazidime administration in preterm infants during the first week of life should be based

Childhood kidney outcomes in relation to fetal blood flow and kidney size

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Fetal and infant growth patterns and kidney function at school age

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Genome-wide profiling of blood pressure in adults and children

Hypertension is an important determinant of cardiovascular morbidity and mortality and has a substantial heritability, which is likely of polygenic origin. The aim of this study was to assess to what extent multiple common genetic variants contribute to blood pressure regulation in both adults and children and to assess overlap in variants between differe