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

Renal and systemic prostanoid activity was assessed in various renal tubular disorders, using mass spectrometric determination of urinary excretion rates of primary prostaglandins (PGE2, PGF2 alpha, 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.