Methylxanthines increase renal calcium excretion in preterm infants

Biol Neonate. 1995;68(3):169-74. doi: 10.1159/000244234.


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/12 h) or caffeine (loading dose 10 mg/kg i.v., maintenance dose 2.5 mg/kg/12 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 micrograms/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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Caffeine / pharmacology*
  • Calcium / urine*
  • Humans
  • Infant, Newborn
  • Infant, Premature / urine*
  • Kidney / drug effects
  • Kidney / metabolism*
  • Theophylline / pharmacology*


  • Caffeine
  • Theophylline
  • Calcium