title: The renal adverse effects of ibuprofen are not mediated  by AQP2 water channels.
abstract: The aim of this study was to determine (1) whether ibuprofen treatment in very preterm infants causes an increase in the renal water channel aquaporin-2 (AQP2) activity in the collecting duct via prostaglandin synthesis inhibition and (2) whether AQP2 activity remains disturbed long after ibuprofen treatment has ended. This was a prospective study involving premature infants with a gestation age of 27-31 weeks who received treatment between December 2005 and August 2006 in a tertiary Neonatal Intensive Care Unit. Each ibuprofen-treated infant was matched to two controls. Renal glomerular and tubular function were evaluated weekly for 1 month, and urinary AQP2 was measured by immuno-dotting. In total, 166 longitudinal samples were analyzed in 36 infants. Median [interquartile range] gestational age and birthweight were 28 [27.0-29.5] weeks and 1160 [1041-1242] g, respectively. Perinatal factors were similar in both groups. Urine output was significantly decreased in the ibuprofen-treated infants during the treatment. The urinary AQP2 level decreased significantly from day 2 to day 7 in both groups and was similar thereafter for the first month of life in ibuprofen-treated and control groups. Based on our results, we conclude that ibuprofen-induced oligo-anuria is not associated with a change in AQP2 activity and that ibuprofen does not affect AQP2 activity during the first month of life in very preterm neonates.
authors.affiliation: Neonatal Department, Maternite Regionale Universitaire, 54042 Nancy, France.
authors.forename: Rachel
authors.initials: R
authors.lastname: Vieux
authors.forename: Marina
authors.initials: M
authors.lastname: Zelenina
authors.forename: Anita
authors.initials: A
authors.lastname: Aperia
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Hascoët
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000009:adverse effects*; D051399:Aquaporin 2 / Q000378:metabolism* / Q000652:urine; D001724:Birth Weight; D005260:Female; D005865:Gestational Age; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007052:Ibuprofen / Q000009:adverse effects*; D007231:Infant, Newborn; D007234:Infant, Premature / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D007677:Kidney Function Tests; D008297:Male; D011446:Prospective Studies; D014555:Urination Disorders / Q000139:chemically induced* / Q000378:metabolism
chemical_list: D018712:Analgesics, Non-Narcotic; D051399:Aquaporin 2; D007052:Ibuprofen
references.citation: J Am Soc Nephrol. 2004 Dec;15(12):2998-3005
references.pmid: 15579502
references.citation: Proc Natl Acad Sci U S A. 1995 Feb 14;92(4):1013-7
references.pmid: 7532304
references.citation: Pediatr Res. 2000 Nov;48(5):600-5
references.pmid: 11044478
references.citation: Pediatr Nephrol. 2000 Mar;14(3):227-39
references.pmid: 10752764
references.citation: Pediatr Nephrol. 2006 Jul;21(7):947-52
references.pmid: 16773405
references.citation: Pediatr Res. 1994 Nov;36(5):572-7
references.pmid: 7877873
references.citation: Early Hum Dev. 1998 Apr 17;51(1):31-7
references.pmid: 9570029
references.citation: Pediatr Nephrol. 2006 Oct;21(10):1389-92
references.pmid: 16897006
references.citation: Cochrane Database Syst Rev. 2008 Jan 23;(1):CD003481
references.pmid: 18254020
references.citation: Biol Neonate. 2002;82(1):17-21
references.pmid: 12119536
references.citation: Am J Physiol. 1996 Aug;271(2 Pt 2):F414-22
references.pmid: 8770174
references.citation: Am J Physiol. 1996 Aug;271(2 Pt 2):F461-8
references.pmid: 8770180
references.citation: Am J Physiol Renal Physiol. 2000 Mar;278(3):F388-94
references.pmid: 10710543
references.citation: Arch Dis Child Fetal Neonatal Ed. 1997 Jul;77(1):F36-40
references.pmid: 9279181
references.citation: Acta Paediatr Scand Suppl. 1983;305:70-6
references.pmid: 6351537
references.citation: J Pediatr. 1995 Nov;127(5):774-9
references.pmid: 7472835
references.citation: Am J Physiol. 1995 Jun;268(6 Pt 1):C1546-51
references.pmid: 7541941
references.citation: Clin Perinatol. 1986 Jun;13(2):377-401
references.pmid: 3720168
references.citation: Pediatr Nephrol. 2010 Feb;25(2):267-74
references.pmid: 19902266
references.citation: Physiol Rev. 2002 Jan;82(1):205-44
references.pmid: 11773613
references.citation: Am J Physiol. 1977 May;232(5):F416-23
references.pmid: 860762
references.citation: Curr Opin Pediatr. 1994 Apr;6(2):154-7
references.pmid: 8032394
references.citation: Semin Perinatol. 2002 Dec;26(6):398-405
references.pmid: 12537310
references.citation: J Am Soc Nephrol. 1997 Oct;8(10):1502-9
references.pmid: 9335377
references.citation: J Clin Pharm Ther. 2005 Apr;30(2):121-32
references.pmid: 15811164
references.citation: Am J Physiol. 1981 Jun;240(6):F471-80
references.pmid: 7018256
references.citation: J Physiol. 1980 Jan;298:371-81
references.pmid: 7359417
references.citation: Nephron Physiol. 2006;104(4):121-5
references.pmid: 16902321
references.citation: Acta Paediatr Scand. 1981 Mar;70(2):183-7
references.pmid: 7015783
references.citation: Arch Dis Child Fetal Neonatal Ed. 2005 Sep;90(5):F419-22
references.pmid: 16113155
references.citation: J Pediatr. 1994 Oct;125(4):625-7
references.pmid: 7931888
references.citation: Scand J Clin Lab Invest. 2001;61(8):631-40
references.pmid: 11768323
references.citation: Pediatr Clin North Am. 1987 Jun;34(3):571-90
references.pmid: 3588043
references.citation: Acta Paediatr Scand. 1984 Nov;73(6):717-21
references.pmid: 6524361
references.citation: Br J Clin Pharmacol. 2007 Jan;63(1):75-84
references.pmid: 16869817