Renal prostacyclin biosynthesis is reduced in children with hemolytic-uremic syndrome in the context of systemic platelet activation.

Abstract

Previous studies have reported various abnormalities in prostacyclin (PGI2) synthesis and metabolism in hemolytic-uremic syndrome (HUS). However, the conclusions of most of these studies are based on in vitro or ex vivo experiments that only give an indirect estimate of the actual biosynthesis in vivo. We studied the urinary excretion of PGI2 metabolites, taken as a marker of the actual biosynthesis, in six children with HUS during the acute phase of the disease and again when remission was achieved. Eight age- and sex-matched healthy children were studied as controls. Since HUS is also associated with platelet activation and consumption, we also studied the urinary excretion of thromboxane A2 (TxA2) metabolites. Urinary PGI2 and TxA2 metabolites were assessed by radioimmunoassay after high-performance liquid chromatography (HPLC) purification. Urinary excretion of the PGI2 hydrolysis product, 6-keto-PGF1 alpha, was significantly reduced in children with acute HUS as compared with controls, indicating a defective renal synthesis of PGI2. A significant inverse correlation was found between urinary 6-keto-PGF1 alpha and blood urea nitrogen (BUN), as well as plasma creatinine. At remission, urinary 6-keto-PGF1 alpha levels increased to values higher than those of controls. By contrast, the urinary excretion of the major PGI2 beta-oxidation product, 2,3-dinor-6-keto-PGF1 alpha, was comparable to controls, indicating normal systemic PGI2 biosynthesis. The urinary excretion of both TxA2 hydrolysis product, TxB2, and the major beta-oxidation metabolite, 2,3-dinor-TxB2, were lower than normal in the acute phase of HUS if expressed as absolute values.(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: M Noris, A Benigni, R Siegler, F Gaspari, F Casiraghi, M L Mancini, G Remuzzi
• Journal: American journal of kidney diseases : the official journal of the National Kidney Foundation (Am J Kidney Dis) Vol. 20 Issue 2 Pg. 144-9 (Aug 1992) ISSN: 0272-6386 [Print] United States
• PMID: 1496967 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Prostaglandins
• Thromboxane B2
• Thromboxane A2
• Epoprostenol

Topics

• Child
• Child, Preschool
• Epoprostenol (biosynthesis)
• Female
• Hemolytic-Uremic Syndrome (blood, metabolism, urine)
• Humans
• Kidney (metabolism)
• Linear Models
• Male
• Platelet Activation
• Prostaglandins (urine)
• Thromboxane A2 (metabolism)
• Thromboxane B2 (urine)