Urinary aquaporin-2 excretion during ibuprofen or indomethacin treatment in preterm infants with patent ductus arteriosus

Acta Paediatr. 2011 Jan;100(1):59-66. doi: 10.1111/j.1651-2227.2010.01943.x.


Aim: Water channel AQP2 is the target for vasopressin (AVP) and a major determinant of urinary concentrating capacity. In mature kidneys, prostaglandins counteract the effect of AVP on AQP2 expression at functional sites. We investigated whether disturbances in water homeostasis in infants with patent ductus arteriosus (PDA) treated with prostaglandin inhibitors can be attributed to activation of AQP2.

Methods: In 53 infants with symptomatic PDA (gestational age 24-33 weeks), 30 receiving ibuprofen and 23 indomethacin starting at 2-15 days of life, clinical and biochemical data were collected before treatment and after each dose of the drugs. Urinary AQP2 was determined by dot immunoblotting.

Results: Urinary AQP2 level and osmolality were decreased in both groups. Urinary osmolality was overall low and correlated inversely with fluid uptake. In ibuprofen group, there was no correlation of AQP2 level with urinary osmolality.

Conclusion: There was no AQP2 upregulation in the infants. The low urinary osmolality and dissociation between urinary osmolality and urinary AQP2 level indicate that the fluid retention sometimes observed in PDA infants treated with prostaglandin inhibitors is not caused by increased levels of functional AQP2. Thus, knowledge about the renal physiology of the adult cannot always be transferred to the infant kidney.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aquaporin 2 / urine*
  • Cardiovascular Agents / therapeutic use*
  • Ductus Arteriosus, Patent / drug therapy*
  • Ductus Arteriosus, Patent / urine
  • Female
  • Gestational Age
  • Humans
  • Ibuprofen / therapeutic use*
  • Indomethacin / therapeutic use*
  • Infant, Newborn
  • Infant, Premature
  • Infant, Premature, Diseases / drug therapy*
  • Infant, Premature, Diseases / urine
  • Male
  • Osmolar Concentration


  • Aquaporin 2
  • Cardiovascular Agents
  • Ibuprofen
  • Indomethacin