Pediatric Nephrology

, Volume 1, Issue 3, pp 491–497 | Cite as

Role of prostaglandins in hyperprostaglandin E syndrome and in selected renal tubular disorders

  • Hannsjörg W. Seyberth
  • Siegfried J. Königer
  • Wolfgang Rascher
  • P. Gonne Kühl
  • Horst Schweer
International Symposium on Hereditary Nephropathies Heidelberg, 6–8 October, 1986


Renal and systemic prostanoid activity was assessed in various renal tubular disorders, using mass spectrometric determination of urinary excretion rates of primary prostaglandins (PGE2, PGF, PGI2, and TXA2) and their systemically produced index metabolites. Only PGE2 levels (normal range: 2.0–16.4 ng/h per 1.73 m2) are elevated in Bartter syndrome (median: 43.4, range: 6.7–166.3), nephrogenic diabetes insipidus (46.2, 12.1–1290), Fanconi syndrome (96.6, 19.3–135.5), and in a complex tubular disorder in premature infants (40.7, 22.3–132.1), for which the term hyperprostaglandin E syndrome has been introduced. In this disorder with a Bartter-syndrome-like tubulopathy, the systemic features of the disease such as fever, diarrhoea and osteopenia with hypercalciuria were associated with increased systemic PGE2 activity. In most patients the urinary excretion rate of the systemic index metabolite of PGE2 (PGE-M) was markedly elevated (1028, 285–4709; normal range: 104–664 ng/h per 1.73 m2). Hypercalciuria per se was associated neither with increased renal nor with systemic PGE2 hyperactivity. Most problems in infants with hyperprostaglandin E syndrome could be controlled by long-term indomethacin treatment in contrast to the moderate and partial effect of this treatment in patients with Fanconi syndrome. Thus increased PGE2 synthesis plays a major role in the pathogenesis of hyperprostaglandin E syndrome, while in Fanconi syndrome PGE2 hyperactivity in the kidney is a secondary event and only aggravates the water and electrolyte wastage.

Key words

Prostaglandins Tubular disorders Bartter syndrome Nephrogenic diabetes inspidus Hypercalciuria Fanconi syndrome Hyperprostaglandin E syndrome 


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  1. 1.
    Verberckmoes R, van Damme B, Clement J, Amery A, Michielsen P (1976) Bartter's syndrome with hyperplasia of renomedullary cells: successful treatment with indomethacin. Kidney Int 9: 302–307PubMedGoogle Scholar
  2. 2.
    Fichman MP, Telfer N, Zia P, Speckart P, Golub M, Rude R (1976) Role of prostaglandins in the pathogenesis of Bartter's syndrome. Am J Med 60: 785–797PubMedGoogle Scholar
  3. 3.
    Bartter FC, Gill JR, Frölich JC, Bowden RE, Hollifield JW, Radfar N, Keiser HR, Oates JA, Seyberth HW, Taylor AA (1976) Prostaglandins are overproduced by the kidneys and mediate hyperreninemia in Bartter's syndrome. Trans Assoc Am Physicians 89: 77–91PubMedGoogle Scholar
  4. 4.
    Gill JR (1985) Bartter's syndrome. In: Gonick HC, Buckalew VM (eds) Renal tubular disorders: pathophysiology, diagnosis and management. Dekker, New York, Basel, pp 457–473Google Scholar
  5. 5.
    Stein JH (1985) The pathogenetic spectrum of Bartter's syndrome. Kidney Int 28: 85–93PubMedGoogle Scholar
  6. 6.
    Seyberth HW, Rascher W, Schweer H, Kühl PG, Mehls O, Schärer K (1985) Congenital hypokalemia with hypercalciuria in pretern ibfants: a hyperprostaglandinuric tubular syndrome different from Bartter syndrome. J Pediatr 107: 694–701PubMedGoogle Scholar
  7. 7.
    Seyberth HW, Müller H, Erlenmaier T, Mrongovius R (1980) Mass spectrometric determination of urinary prostaglandins in preterm infants: the basis for an effective and safe regimen for the pharmacological closure of the ductus arteriousus. Eur J Clin Pharmacol 18: 89–92PubMedGoogle Scholar
  8. 8.
    Catella F, Nowak J, FitzGerald GA (1986) Measurement of renal and non-renal eicosanoid synthesis. Am J Med 81 [suppl 2B]: 23–29Google Scholar
  9. 9.
    Güllner H, Bartter FC, Cerletti C, Smith JB, Gill JR (1979) Prostacyclin overproduction in Bartter's syndrome. Lancet II: 2: 767–768Google Scholar
  10. 10.
    Patrono C, Cinotti GA, Ciabattoni G, Pugliese F (1980) Prostaglandins, thromboxanes, and renal physiology: introduction. In: Remuzzi G, Mecca G, de Gaetano G (eds) Hemostasis, prostaglandins, and renal disease. Raven Press, New York, pp 151–157Google Scholar
  11. 11.
    Watson ML, Branch RA, Gill JR, Pates JA, Brash AR (1983) Systemic prostaglandin I2 synthesis is normal in patients with Bartter's syndrome. Lancet II: 1: 368–369Google Scholar
  12. 12.
    Seyberth HW, Müller H, Soeding K, Wille L, Hackenthal E (1983) Urinary excretion rate of 6-keto-prostaglandin F as an index of circulating prostacyclin. Adv Prostaglandin Thromboxane-Leukotriene Res 11: 533–538Google Scholar
  13. 13.
    Boyd RM, Nasjletti A, Heerdt PM, Baer PG (1986) PGI2 synthesis and excretion in dog kidney: evidence for renal PG compartmentalization. Am J Physiol 250: F58-F65PubMedGoogle Scholar
  14. 14.
    Hamberg M, Samuelsson B (1971) On the metabolism of prostaglandins E1 and E2 in man. J Biol Chem 246: 6713–6721PubMedGoogle Scholar
  15. 15.
    Rascher W, Rosendahl W, Henrichs IA, Maier R, Seyberth HW (1987) Congenital nephrogenic diabetes insipidus: vasopressin and prostaglandins in response to treatment with hydrochlorothiazide and indomethacin. Pediatr Nephrol 1: 487–492Google Scholar
  16. 16.
    Schlöndorff D, Ardaillou R (1986) Prostaglandins and other arachidonic acid metabolites in the kidney. Kidney Int 29: 108–119PubMedGoogle Scholar
  17. 17.
    Usberti M, Pecoraro C, Federico S, Cianciaruso B, Guida B, Romano A, Grumetto L, Carbonaro L (1985) Mechanism of action of indomethacin in tubular defects. Pediatr 75: 501–507PubMedGoogle Scholar
  18. 18.
    Chan JCM, Gill JR, Bartter FC (1983) Lack of evidence for a role for prostaglandins in the mediation of impaired urinary concentrating ability in Bartter's syndrome. Nephron 35: 116–119PubMedGoogle Scholar
  19. 19.
    Bétend B, David L, Vincent M, Hermier M, Francois R (1979) Successful indomethacin treatment of two paediatric patients with severe tubulopathies. Helv Paediatr Acta 34: 339–344PubMedGoogle Scholar
  20. 20.
    Haycock GB, Al Dahhan J, Mak RHK, Chantler C (1982) Effect of indomethacin on clinical progress and renal function in cystinosis. Arch Dis Child 57: 934–939PubMedGoogle Scholar
  21. 21.
    Houser M, Zimmerman B, Davidman M, Smith C, Sinaiko A, Fish A (1984) Idiopathic hypercalciuria associated with hyperreninemia and high urinary prostaglandin E. Kidney Int 26: 176–182PubMedGoogle Scholar

Copyright information

© IPNA 1987

Authors and Affiliations

  • Hannsjörg W. Seyberth
    • 1
  • Siegfried J. Königer
    • 1
  • Wolfgang Rascher
    • 1
  • P. Gonne Kühl
    • 1
  • Horst Schweer
    • 1
  1. 1.Kinderklinik der Universität HeidelbergHeidelbergGermany

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