The renal adverse effects of ibuprofen are not mediated  by AQP2 water channels.
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.
Vieux
Rachel
R
Neonatal Department, Maternite Regionale Universitaire, 54042 Nancy, France.
Zelenina
Marina
M
Aperia
Anita
A
Hascoët
Jean-Michel
JM
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
D018712:Analgesics, Non-Narcotic; D051399:Aquaporin 2; D007052:Ibuprofen
J Am Soc Nephrol. 2004 Dec;15(12):2998-3005
15579502
Proc Natl Acad Sci U S A. 1995 Feb 14;92(4):1013-7
7532304
Pediatr Res. 2000 Nov;48(5):600-5
11044478
Pediatr Nephrol. 2000 Mar;14(3):227-39
10752764
Pediatr Nephrol. 2006 Jul;21(7):947-52
16773405
Pediatr Res. 1994 Nov;36(5):572-7
7877873
Early Hum Dev. 1998 Apr 17;51(1):31-7
9570029
Pediatr Nephrol. 2006 Oct;21(10):1389-92
16897006
Cochrane Database Syst Rev. 2008 Jan 23;(1):CD003481
18254020
Biol Neonate. 2002;82(1):17-21
12119536
Am J Physiol. 1996 Aug;271(2 Pt 2):F414-22
8770174
Am J Physiol. 1996 Aug;271(2 Pt 2):F461-8
8770180
Am J Physiol Renal Physiol. 2000 Mar;278(3):F388-94
10710543
Arch Dis Child Fetal Neonatal Ed. 1997 Jul;77(1):F36-40
9279181
Acta Paediatr Scand Suppl. 1983;305:70-6
6351537
J Pediatr. 1995 Nov;127(5):774-9
7472835
Am J Physiol. 1995 Jun;268(6 Pt 1):C1546-51
7541941
Clin Perinatol. 1986 Jun;13(2):377-401
3720168
Pediatr Nephrol. 2010 Feb;25(2):267-74
19902266
Physiol Rev. 2002 Jan;82(1):205-44
11773613
Am J Physiol. 1977 May;232(5):F416-23
860762
Curr Opin Pediatr. 1994 Apr;6(2):154-7
8032394
Semin Perinatol. 2002 Dec;26(6):398-405
12537310
J Am Soc Nephrol. 1997 Oct;8(10):1502-9
9335377
J Clin Pharm Ther. 2005 Apr;30(2):121-32
15811164
Am J Physiol. 1981 Jun;240(6):F471-80
7018256
J Physiol. 1980 Jan;298:371-81
7359417
Nephron Physiol. 2006;104(4):121-5
16902321
Acta Paediatr Scand. 1981 Mar;70(2):183-7
7015783
Arch Dis Child Fetal Neonatal Ed. 2005 Sep;90(5):F419-22
16113155
J Pediatr. 1994 Oct;125(4):625-7
7931888
Scand J Clin Lab Invest. 2001;61(8):631-40
11768323
Pediatr Clin North Am. 1987 Jun;34(3):571-90
3588043
Acta Paediatr Scand. 1984 Nov;73(6):717-21
6524361
Br J Clin Pharmacol. 2007 Jan;63(1):75-84
16869817