Pediatric Nephrology

, Volume 20, Issue 9, pp 1249–1252 | Cite as

Prophylactic theophylline to prevent renal dysfunction in newborns exposed to perinatal asphyxia—a study in a developing country

  • Ahmad Fayez Bakr
Original Article


Renal damage frequently complicates perinatal asphyxia. Renal vasoconstriction due to adenosine metabolite leads to a fall in glomerular filtration rate (GFR) and filtration fraction. This might be inhibited by the nonspecific adenosine receptor antagonist, theophylline. This study was designed to determine whether theophylline could prevent and/or ameliorate renal dysfunction in term neonates with perinatal asphyxia. We randomized 40 severely asphyxiated term infants to receive intravenously a single dose of either theophylline (5 mg/kg; study group: n=20) or placebo (control group: n=20) during the first hour of life. Fluid intake, urine output, serum creatinine, creatinine clearance, GFR, urinary β2 microglobulin (β2 M) and sodium excretion were recorded during the first 5 days of life. The two groups were comparable. No significant difference was reported regarding mechanical ventilatory support, respiratory complications and seizures. Severe renal dysfunction was significantly higher in the control group. Serum creatinine values were less, and creatinine clearance and GFR were significantly higher in the theophylline group from the second day onwards. β2 M excretion was significantly less in the theophylline group, while sodium excretion and hematuria showed no significant difference. Prophylactic theophylline treatment, given early after birth, has beneficial effects in reducing the renal involvement in asphyxiated full-term infants, with no significant changes in central nervous system involvement.


Perinatal asphyxia Theophylline Renal function Neonates Nonspecific adenosine receptor antagonist 


  1. 1.
    Saugstad OD (1998) Practical aspects of resuscitating asphyxiated newborn infants. Eur J Pediatr 157:S11–S15PubMedGoogle Scholar
  2. 2.
    Willis F, Summers J, Minutillo C, Hewitt I (1997) Indices of renal tubular function in perinatal asphyxia. Arch Dis Child Fetal Neonatal Ed 77:F57–F60PubMedGoogle Scholar
  3. 3.
    Behrman RE, Lees MH, Peterson EN (1970) Distribution of the circulation in the normal and asphyxiated fetal primate. Am J Obstet Gynecol 108:956–969PubMedGoogle Scholar
  4. 4.
    Rudolph AM (1984) The fetal circulation and its response to stress. J Dev Physiol 6:11–19PubMedGoogle Scholar
  5. 5.
    Gunn AJ, Gluckman PD, Gunn TR (1998) Selective head cooling in newborn infants after perinatal asphyxia: a safety study. Pediatrics 102:885–892CrossRefPubMedGoogle Scholar
  6. 6.
    Di Pietro A, Proverbio MR, Pescatore L (1989) English translation: evaluation of kidney damage in neonatal anoxia syndrome: a 1-year follow-up. Pediatr Med Chir 11:637–638PubMedGoogle Scholar
  7. 7.
    Churchill PC, Bidani AK (1982) Hypothesis: adenosine mediates hemodynamic changes in renal failure. Med Hypotheses 8:275–285CrossRefPubMedGoogle Scholar
  8. 8.
    Gouyon JB, Guignard JP (1988) Theophylline prevents the hypoxemia-induced renal hemodynamic changes in rabbits. Kidney Int 33:1078–1083PubMedGoogle Scholar
  9. 9.
    Burke TJ, Arnold PE, Gordon JA, Bulger RE (1984) Protective effect of intrarenal calcium membrane blockers before or after renal ischemia: functional, morphological, and mitochondrial studies. J Clin Invest 74:1830–1841PubMedGoogle Scholar
  10. 10.
    Wiesel PH, Semmekrot BA, Grigoras O (1990) Pharmacological doses of atrial natriuretic peptide ameliorate the acute renal dysfunction induced by systemic hypoxemia. J Pharmacol Exp Ther 254:971–975PubMedGoogle Scholar
  11. 11.
    Osswald H (1975) Renal effects of adenosine and their inhibition by theophylline in dogs. Naunyn Schmiedebergs Arch Pharamcol 288:79–86Google Scholar
  12. 12.
    Jenik AG, Ceriani Cernadas JM, Gorensterin A, Ramirez JA et al. (2000) A randomized, double-blind, placebo-controlled trial of the effects of prophylactic theophylline on renal function in term neonates with perinatal asphyxia. Pediatrics 105:e45CrossRefPubMedGoogle Scholar
  13. 13.
    Hall JE, Granger JP, Hester RL (1985) Interactions between adenosine and angiotensin II in controlling glomerular filtration. Am J Physiol 248:F340–F346Google Scholar
  14. 14.
    Gouyon JB, Guignard JP (1988) Functional renal insufficiency: role of adenosine. Biol Neonate 53:237–242PubMedGoogle Scholar
  15. 15.
    Edlund A, Ohlsen H, Sollevi A (1994) Renal effects of local infusion of adenosine in man. Clin Sci 87:143–149PubMedGoogle Scholar
  16. 16.
    Prada J, Churchill P, Bidani A (1986) Protective effect of theophylline in endotoxin-mediated acute renal failure (ARF) in rats. Kidney Int 29:308Google Scholar
  17. 17.
    Deray G, Martinez F, Cacoub P, Baumelou B, Baumelou A, Jacobs C (1990) A role for adenosine calcium and ischemia in radiocontrast-induced intrarenal vasoconstriction. Am J Nephrol 10:316–322PubMedGoogle Scholar
  18. 18.
    Erley CM, Duda SH, Schlepckow S (1994) Adenosine antagonist theophylline prevents the reduction of glomerular filtration rate after contrast media application. Kidney Int 45:1425–1431PubMedGoogle Scholar
  19. 19.
    Huet F, Semama D, Grimaldi M, Guignard JP, Gouyon JB (1995) Effects of theophylline on renal insufficiency in neonates with respiratory distress syndrome. Intensive Care Med 21:511–514PubMedGoogle Scholar
  20. 20.
    Huber W, Ilgmann K, Page M, Hennig M (2002) Effect of theophylline on contrast material-nephropathy in patients with chronic renal insufficiency: controlled, randomized, double-blinded study. Radiology 223:772–779Google Scholar
  21. 21.
    Kramer BK, Preuner J, Ebenburger A (2002) Lack of renoprotective effect of theophylline during aortocoronary bypass surgery. Nephrol Dial Transplant 17:910–915Google Scholar
  22. 22.
    Kelly DH, Shannon DC (1981) Treatment of apnea and excessive periodic breathing in the full-term infant. Pediatrics 68:183–186PubMedGoogle Scholar
  23. 23.
    Gouyon JB, Guignard JP (1987) Renal effects of theophylline and caffeine in newborn rabbits. Pediatr Res 21:615–618PubMedGoogle Scholar
  24. 24.
    Laudignon N, Farri E, Beharry K, Rex J, Aranda JV (1990) Influence of adenosine on cerebral blood flow during hypoxic hypoxia in the newborn piglet. J Appl Physiol 68:1534–1541PubMedGoogle Scholar
  25. 25.
    Scheinberg P (1976) Correlation of brain monoamines and energy metabolism changes. In: American Neurological Association, American Heart Association: Stroke Council, Princeton Conference (1976). Cerebrovascular diseases. Raven Press, New York, pp 167–171Google Scholar
  26. 26.
    Bona E, Ådén U, Fredholm BB, Hagberg H (1995) Reduction of neonatal hypoxic-ischemic brain damage after acute adenosine antagonist treatment. Pediatr Res 37:376AGoogle Scholar
  27. 27.
    Gidday JM, Fitzgibbons JC, Shah AR, Kraujalis MJ, Park TS (1995) Reduction in cerebral ischemic injury in the newborn rat by potentiation of endogenous denosine. Pediatr Res 38:306–311PubMedGoogle Scholar
  28. 28.
    Dux E, Fastbom J, Ungerstedt U, Rudolphi K, Fredholm BB (1990) Protective effect of adenosine and a novel xanthine derivative propentofylline on the cell damage after bilateral carotid occlusion in the gerbil hippocampus. Brain Res 516:248–256CrossRefPubMedGoogle Scholar

Copyright information

© IPNA 2005

Authors and Affiliations

  • Ahmad Fayez Bakr
    • 1
  1. 1.Department of Pediatrics, Newborn UnitFaculty of Medicine, University of AlexandriaEgypt

Personalised recommendations