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Changes in urinary PGE2 after ibuprofen treatment in preterm infants with patent ductus arteriosus

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Abstract

Purpose

To investigate changes in urinary PGE2 after ibuprofen treatment in preterm infants with patent ductus arteriosus (PDA).

Methods

Twenty preterm infants with a hemodynamically significant PDA (gestational age, 28.6 ± 2.3 weeks) and 20 controls (gestational age, 30.4 ± 1.5 weeks) were prospectively enrolled at 48–72 h of life. After enrollment, the former underwent conventional ibuprofen-lysine treatment. At 48–72 h (T0) and 108–144 h of life (T1), urine samples were noninvasively collected in both groups to measure urinary PGE2 concentrations (enzyme immunoassay method), and renal function was investigated.

Results

Urinary PGE2 decreased significantly both in ibuprofen-treated patients (66.95 ± 16.78 vs. 27.15 ± 17.92 pg/mL, P < 0.001) and in controls (71.7 ± 16.2 vs. 53.2 ± 18.4 pg/mL, P < 0.001) from T0 to T1. However, urinary PGE2 at T1 was significantly lower (P < 0.001) in the ibuprofen group compared to the control group. Acute renal failure occurred in three ibuprofen-treated patients (15%).

Conclusions

Ibuprofen markedly reduces (59.4%) urinary PGE2 and may alter renal function in the newborn.

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References

  1. Danilowicz D, Rudolph AM, Hoffman JI (1966) Delayed closure of the ductus arteriosus in premature infants. Pediatrics 37:74–78

    PubMed  CAS  Google Scholar 

  2. Kitterman JA, Edmunds LH Jr, Gregory GA et al (1972) Patent ducts arteriosus in premature infants. Incidence, relation to pulmonary disease and management. N Engl J Med 287:473–477

    PubMed  CAS  Google Scholar 

  3. Clyman RI (2000) Ibuprofen and patent ductus arteriosus. N Engl J Med 343:728–730

    Article  PubMed  CAS  Google Scholar 

  4. Schlondorff D (1993) Renal complications of nonsteroidal anti-inflammatory drugs. Kidney Int 44:643–653

    Article  PubMed  CAS  Google Scholar 

  5. FitzGerald GA, Patrono C (2001) The coxibs, selective inhibitors of cyclooxygenase-2. N Engl J Med 345:433–442

    Article  PubMed  CAS  Google Scholar 

  6. Van Overmeire B, Follens I, Hartmann S et al (1997) Treatment of patent ductus arteriosus with ibuprofen. Arch Dis Child 76:179–184

    Google Scholar 

  7. SoRelle R (2000) Ibuprofen as effective as indomethacin for patent ductus arteriosus. Circulation 102:9007–9008

    Google Scholar 

  8. Lago P, Bettiol T, Salvatori S et al (2002) Safety and efficacy of ibuprofen versus indomethacin in preterm infants treated for patent ductus arteriosus: a randomised controlled trial. Eur J Pediatr 161:202–207

    Article  PubMed  CAS  Google Scholar 

  9. Pezzati M, Vangi V, Biagiotti R et al (1999) Effect of indomethacin and ibuprofen on mesenteric and renal blood flow in preterm infants with patent ductus arteriosus. J Pediatr 135:733–738

    Article  PubMed  CAS  Google Scholar 

  10. Van Overmeire B, Smets K, Lecoutere D et al (2000) A comparison of ibuprofen and indomethacin for closure of patent ductus arteriosus. N Engl J Med 343:674–681

    Article  PubMed  Google Scholar 

  11. Gimeno Navarro A, Modesto Alapont V, Morcillo Sopena F et al (2007) Ibuprofen versus indomethacin in the preterm persistent patent ductus arteriosus therapy: review and meta-analysis (in Spanish). An Pediatr (Barc) 67:309–318

    Article  CAS  Google Scholar 

  12. Heyman E, Morag I, Batash D et al (2003) Closure of patent ductus arteriosus with oral ibuprofen suspension in premature newborns: a pilot study. Pediatrics 112:354

    Article  Google Scholar 

  13. Guignard JP (2002) The adverse renal effects of prostaglandin-synthesis inhibitors in the newborn rabbit. Semin Perinatol 26:398–405

    Article  PubMed  Google Scholar 

  14. Cuzzolin L, Fanos V, Pinna B et al (2006) Postnatal renal function in preterm newborns: a role of diseases, drugs and therapeutic interventions. Pediatr Nephrol 21:931–938

    Article  PubMed  Google Scholar 

  15. Erdeve O, Sarici SU, Sari E et al (2008) Oral-ibuprofen-induced acute renal failure in a preterm infant. Pediatr Nephrol 23:1565–1567

    Article  PubMed  Google Scholar 

  16. Bennett A, Villa G (2000) Nimesulide: a nonsteroidal anti-inflammatory drug that preferentially inhibits cyclooxygenase-2, and has various unique pharmacological activities. Expert Opin Pharmacoth 1:277–286

    Article  CAS  Google Scholar 

  17. Breyer MD, Zhang Y, Guan Y et al (1998) Regulation of renal function by prostaglandin E receptors. Kidney Int 54:S88–S94

    Article  Google Scholar 

  18. Currie MG, Needleman P (1984) Renal arachidonic acid metabolism. Annu Rev Physiol 46:327–341

    Article  PubMed  CAS  Google Scholar 

  19. Breyer MD, Breyer RM (2000) Prostaglandin receptors: their role in regulating renal function. Curr Opin Nephrol Hypertens 9:23–29

    Article  PubMed  CAS  Google Scholar 

  20. Klahr S, Purkerson ML (1994) The pathophysiology of obstructive nephropathy: the role of vasoactive compounds in the hemodynamic and structural abnormalities of the obstructed kidney. Am J Kidney Dis 23:219–223

    PubMed  CAS  Google Scholar 

  21. Cuzzolin L, Dal Cerè M, Fanos V (2001) NSAID-induced nephrotoxicity from the fetus to the child. Drug Safety 24:9–18

    Article  PubMed  CAS  Google Scholar 

  22. Giniger RP, Buffat C, Millet V et al (2007) Renal effects of ibuprofen for the treatment of patent ductus arteriosus in premature infants. J Matern Fetal Neonatal Med 20:275–283

    Article  PubMed  CAS  Google Scholar 

  23. Catella F, Nowak J, Fitzgerald GA (1986) Measurements of renal and non-renal eicosanoid synthesis. Am J Med 81:23–29

    Article  PubMed  CAS  Google Scholar 

  24. Walker RD, Garin EH (1990) Urinary prostaglandin E2 in patients with vesicoureteral reflux. Child Nephrol Urol 10:18–21

    PubMed  CAS  Google Scholar 

  25. Antonucci R, Cuzzolin L, Arceri A et al (2005) Renal PGE2 in preterm infants: a possible role in the adaptation to extrauterine life. Pediatr Res 58:356

    Google Scholar 

  26. Antonucci R, Cuzzolin L, Arceri A et al (2007) Urinary prostaglandin E2 in the newborn and infant. Prostaglandins Other Lipid Mediat 84:1–13

    Article  PubMed  CAS  Google Scholar 

  27. Skelton R, Evans N, Smythe J (1994) A blinded comparison of clinical and echocardiographic evaluation of the preterm infant for ductus arteriosus. J Paediatr Child Health 30:406–411

    Article  PubMed  CAS  Google Scholar 

  28. Fell JM, Thakkar H, Newman DJ et al (1997) Measurement of albumin and low molecular weight proteins in the urine of newborn infants using a cotton wool ball collection method. Acta Paediatr 86:518–522

    Article  PubMed  CAS  Google Scholar 

  29. Bose CL, Laughon MM (2007) Patent ductus arteriosus: lack of evidence for common treatments. Arch Dis Child Fetal Neonatal Ed 92:F498–F502

    Article  PubMed  Google Scholar 

  30. Ohlsson A, Walia R, Shah S (2008) Ibuprofen for the treatment of patent ductus arteriosus in preterm and/or low birth weight infants. Cochrane Database Syst Rev (1):CD00348

  31. Thomas RL, Parker GC, Van Overmeire B et al (2005) A meta-analysis of ibuprofen versus indomethacin for closure of patent ductus arteriosus. Eur J Pediatr 164:135–140

    Article  PubMed  CAS  Google Scholar 

  32. Allegaert K, Rayyan M, Anderson BJ (2006) Impact of ibuprofen administration on renal drug clearance in the first weeks of life. Methods Find Exp Clin Pharmacol 28:519–522

    Article  PubMed  CAS  Google Scholar 

  33. Fanos V, Benini D, Verlato G et al (2005) Efficacy and renal tolerability of ibuprofen vs. indomethacin in preterm infants with patent ductus arteriosus. Fundam Clin Pharmacol 19:187–193

    Article  PubMed  CAS  Google Scholar 

  34. Lin YJ, Tsai YJ, Chen JS et al (1995) Renal effects and urinary excretion of prostaglandin following indomethacin therapy in premature infants with patent ductus arteriosus. Acta Pediatr Sin 36:104–107

    CAS  Google Scholar 

  35. Agostiniani R, Mariotti P, Cataldi L et al (2002) Role of renal PGE2 in the adaption from foetal to extrauterine life in term and preterm infants. Prostaglandins Leukot Essent Fatty Acids 67:373–377

    Article  PubMed  CAS  Google Scholar 

  36. Ojala R, Ala-Houhala M, Ahonen S et al (2001) Renal follow up of premature infants with and without perinatal indomethacin exposure. Arch Dis Child Fetal Neonatal Ed 84:F28–F33

    Article  PubMed  CAS  Google Scholar 

  37. Rodriguez MM, Gomez AH, Abitbol CL et al (2004) Histomorphometric analysis of postnatal glomerulogenesis in extremely preterm infants. Pediatr Dev Pathol 7:17–25

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pediatrics and Clinical Medicine-Section of Neonatal Intensive Care Unit, University of Cagliari, Via Ospedale 119, 09124, Cagliari, Italy

    R. Antonucci, A. Arceri, A. Dessì & V. Fanos

  2. Department of Medicine and Public Health-Section of Pharmacology, University of Verona, Policlinico G.B. Rossi, Verona, Italy

    L. Cuzzolin

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  1. R. Antonucci
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  2. L. Cuzzolin
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  3. A. Arceri
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  4. A. Dessì
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  5. V. Fanos
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Correspondence to R. Antonucci.

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Antonucci, R., Cuzzolin, L., Arceri, A. et al. Changes in urinary PGE2 after ibuprofen treatment in preterm infants with patent ductus arteriosus. Eur J Clin Pharmacol 65, 223–230 (2009). https://doi.org/10.1007/s00228-008-0586-3

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  • DOI: https://doi.org/10.1007/s00228-008-0586-3

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