Effects of Theophylline on Renal Function in Premature Infants

Mazkereth, Ram; Laufer, J; Jordan, Stanley C.; Pomerance, Jeffrey J.; Boichis, H; Reichman, Brian

doi:10.1055/s-2007-994095

Cited by 28 publications

(21 citation statements)

References 20 publications

(24 reference statements)

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“…Infants who received frusemide [16,17] and theophylline [18,19] had significantly higher UCa/Cr as previously reported. Infants on dexamethasone also had higher UCa/Cr, but this did not achieve statistical significance, in contrast to the data of Kamitsuka et al [20], perhaps because of the relatively small numbers in this study.…”

Section: Discussionsupporting

confidence: 77%

“…A recent retrospective study of babies born at <37 weeks gestation reported that the incidence of NC was 0.73% (1.7% for VLBW infants) [15]. Factors known to influence UCa excretion in the preterm infant include frusemide [16,17], theophylline [18,19], and dexamethasone [20]. Furosemide has also been shown to increase UPO 4 excretion in VLBW infants [17].…”

Section: Introductionmentioning

confidence: 99%

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Urinary excretion of calcium and phosphate in preterm infants

et al. 2004

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The aims of this study were to determine reference ranges for the urinary calcium (UCa/Cr) and phosphate (UPO(4)/Cr) creatinine ratios and to study factors influencing these ratios in a representative population of preterm infants managed according to current nutritional guidelines. Spot urine samples were obtained from 186 preterm infants (gestation 24-34 weeks) for measurement of UCa/Cr and UPO(4)/Cr ratios as part of a routine metabolic bone screening program, once every 2-4 weeks from the 3rd to the 18th week of life. Data were also collected on gender, appropriate or small for gestational age (SGA), nutrition [total parenteral nutrition (TPN), preterm or term formula, and breast milk], plasma Ca, P0(4), urea, and electrolytes and on the use of drugs (frusemide, dexamethasone, and theophylline). Data from infants treated with any of these three drugs were analyzed separately and not included in establishing the reference ranges for UCa/Cr and UPO(4)/Cr. The mean gestational age of the study population was 28 weeks (range 24-34 weeks). The 95th percentile for UCa/Cr at 3 weeks of age was 3.8 mmol/mmol and decreased significantly with increasing postnatal age (P<0.001). The 95th per-centile for UPO(4)/Cr was 26.69 mmol/mmol at 3 weeks of age, but this did not change significantly with increasing postnatal age (P=0.296). On univariate analysis there was no significant association of UCa/Cr and UPO(4)/Cr with gender and type of enteral nutrition. The UCa/Cr was lower in infants who were SGA (P=0.013) and with low plasma Ca (P=0.008). Infants on TPN had significantly higher UCa/Cr (P =0.019) and lower UPO(4)/Cr ratios(P<0.001). Multivariate analysis confirmed the decrease in UCa/Cr ratio with increasing postnatal age, but the SGA effect was eliminated. The use of furosemide(P<0.001) and theophylline (P=0.003) was associated with a significant increase in the UCa/Cr ratio. The use of dexamethasone was also associated with an increase in UCa/Cr ratio, but this did not achieve statistical significance (P=0.339). The use of furosemide, theophylline,and dexamethasone had no effect on UPO(4)/Cr. We report a reference range for UCa/Cr and UPO(4)/Cr ratios and factors influencing these ratios in a representative population of preterm infants between 24 and 34 weeks gestation, managed according to current nutritional guide-lines.

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Section: Discussionsupporting

confidence: 77%

Section: Introductionmentioning

confidence: 99%

Urinary excretion of calcium and phosphate in preterm infants

et al. 2004

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“…An increase in urine calcium and sodium excretion was previously reported in prema tures treated with theophylline during 4 weeks postnatal age by Rowe et al [9], Furthermore, Mazkereth et al [10] found a similar effect in prematures 24 h after a loading aminophylline dose, which was associated with an in crease in urine FeNa. Our study design showed hypercalciuria with the use of both methylxanthine derivatives theophylline and caf- feine, after a 5-day course.…”

Section: Discussionsupporting

confidence: 58%

Methylxanthines Increase Renal Calcium Excretion in Preterm Infants

Zanardo¹,

Dani²,

Trevisanuto³

et al. 1995

Neonatology

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To determine the effect of a short course of methylxanthines on renal function and on urinary calcium excretion, 20 premature neonates affected by apnea or moderate respiratory distress syndrome were randomly assigned to either a theophylline treatment or to a caffeine treatment group. The protocol included a 24-hour pretreatment study period (I) and a subsequent 24-hour period (II) following 5 days of theophylline (loading dose 5 mg/kg i.v., maintenance dose 2.5 mg/kg/l2 h) or caffeine (loading dose 10 mg/kg i.v., maintenance dose 2.5 mg/kg/l2 h) administration. Pre- and postxanthine treatment serum sodium, potassium, calcium and phosphorus remained stable, while serum creatinine decreased significantly (p < 0.05). Furthermore, from period I to period II, sodium urine excretion, fractional Na excretion and creatinine clearance remained statistically comparable in both study groups, along with a significant increase (p < 0.05) in calciuria, urinary Ca/creatinine and urinary Ca/Na. Predose caffeine and theophylline serum levels, assessed on the 5th day of treatment, were 12.8 ± 1.8 and 7.9 ± 1.7 μg/ml, respectively. Compared to control healthy untreated prematures, the studied premature infants showed a statistically significant increase in urine calcium excretion (10- to 15-fold), which was more evident in the theophylline group. Our data suggest further investigation to determine the long-term renal effects of methylxanthines in premature neonates, to improve assessment of the risk of nephrocalcinosis and osteopenia, in particular in association with various diuretic therapies.

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“…As a result, the renal blood flow and glomerular filtration rate decrease, leading to the occurrence of NC. 32,33 In this study, the duration of theophylline treatment was significantly longer in the NC group in the univariate analysis, but not in the multivariate analysis.…”

Section: Discussioncontrasting

confidence: 52%

Risk Factors and Outcome of Nephrocalcinosis in Very Low Birth Weight Infants

et al. 2015

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� Original Article � furosemide therapy in 1982. Among different studies, the prevalence of NC ranged from 7 to 41% in very low birth weight (VLBW) infants with a gestational age less than 32 weeks. [3][4][5][6][7][8][9] The etiology of NC is multifactorial including low gestational age and birth weight. Male sex, family history, white race, mechanical ventilation, oxygen therapy, bronchopulmonary dysplasia (BPD), the use of furosemide, methylxanthine, dexamethasone, gentamicin, total parenteral nutrition (TPN), acidosis, hypercalcemia, hypophosphatemia, hypercalciuria, hyperoxaluria, hyperuricuria, and hypocitruria are associated with development of NC. Purpose: The aim of this study was to determine the incidence, risk factors, and long-term outcome of nephrocalcinosis in very low birth weight (VLBW) infants. Methods: A retrospective chart review was performed in VLBW infants between 2006 and 2012 in the neonatal intensive care unit. Results:The incidence of nephrocalcinosis in VLBW infants was 10.2%. By univariate analysis, oligohydramnios and use of antenatal steroids were more frequent in the nephrocalcinosis group. In the nephrocalcinosis group, the gestational age and birth weight were lower and there were more number of female infants. Also, the initial blood pH, the lowest systolic blood pressure, and urine output on the first day of life were lower and bronchopulmonary dysplasia, sepsis, and urinary tract infection were more prevalent in the nephrocalcinosis group. The use of dexamethasone or ibuprofen and the lowest levels of phosphorus, protein and albumin were significantly lower in the nephrocalcinosis group. By binary logistic regression analysis, the use of antenatal steroids, female sex, 5-minute Apgar score, duration of oxygen therapy and total parenteral nutrition, and the lowest albumin level were found to be significant risk factors for nephrocalcinosis. Overall, the resolution rate was 64.1% and 88.6% within 12 months and 18 months, respectively. Conclusions:The incidence of nephrocalcinosis in VLBW infants showed increasing trend. The risk factors of nephrocalcinosis were parameters for sick VLBW infants. Although the prognosis of nephrocalcinosis was relatively good, we should pay close attention to the development of complication.

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Effects of Theophylline on Renal Function in Premature Infants

Cited by 28 publications

References 20 publications

Urinary excretion of calcium and phosphate in preterm infants

Urinary excretion of calcium and phosphate in preterm infants

Methylxanthines Increase Renal Calcium Excretion in Preterm Infants

Risk Factors and Outcome of Nephrocalcinosis in Very Low Birth Weight Infants

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