Renal and systemic prostanoid activity was assessed in various renal tubular disorders, using mass spectrometric determination of urinary excretion rates of primary prostaglandins (PGE2, PGF2α, 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.
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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: 302–307
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: 785–797
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: 77–91
Gill JR (1985) Bartter's syndrome. In: Gonick HC, Buckalew VM (eds) Renal tubular disorders: pathophysiology, diagnosis and management. Dekker, New York, Basel, pp 457–473
Stein JH (1985) The pathogenetic spectrum of Bartter's syndrome. Kidney Int 28: 85–93
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: 694–701
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: 89–92
Catella F, Nowak J, FitzGerald GA (1986) Measurement of renal and non-renal eicosanoid synthesis. Am J Med 81 [suppl 2B]: 23–29
Güllner H, Bartter FC, Cerletti C, Smith JB, Gill JR (1979) Prostacyclin overproduction in Bartter's syndrome. Lancet II: 2: 767–768
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 151–157
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: 368–369
Seyberth HW, Müller H, Soeding K, Wille L, Hackenthal E (1983) Urinary excretion rate of 6-keto-prostaglandin Ftα as an index of circulating prostacyclin. Adv Prostaglandin Thromboxane-Leukotriene Res 11: 533–538
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-F65
Hamberg M, Samuelsson B (1971) On the metabolism of prostaglandins E1 and E2 in man. J Biol Chem 246: 6713–6721
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: 487–492
Schlöndorff D, Ardaillou R (1986) Prostaglandins and other arachidonic acid metabolites in the kidney. Kidney Int 29: 108–119
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: 501–507
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: 116–119
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: 339–344
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: 934–939
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: 176–182
Supported by the Deutsche Forschungsgemeinschaft (Se 263/9-1). H. W. Seyberth is in receipt of a Heisenberg Stipend from the Deutsche Forschungsgemeinschaft
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Seyberth, H.W., Königer, S.J., Rascher, W. et al. Role of prostaglandins in hyperprostaglandin E syndrome and in selected renal tubular disorders. Pediatr Nephrol 1, 491–497 (1987). https://doi.org/10.1007/BF00849259
- Tubular disorders
- Bartter syndrome
- Nephrogenic diabetes inspidus
- Fanconi syndrome
- Hyperprostaglandin E syndrome