Abnormal prostanoid metabolism in lupus nephritis and the effects of a thromboxane A 2 synthetase inhibitor, DP-1904

Tadashi Yoshida, Y. Ichikawa, T. Tojo, M. Homma

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Abstract

Abnormalities of prostanoid metabolism, which may affect renal function, were studied in lupus nephritis. The subjects were 31 patients with lupus nephritis, ten with non-renal SLE, and four with renal, non-SLE collagen disease. Urinary levels of various prostanoids, thromboxane B 2 (TXB 2), 11-dehydro-TXB 2, 6-keto-PGF1α,2,3-dinor-6-keto-PGF1α and PGE 2, and plasma level of 11-dehydro-TXB 2 were determined. The effects of four days' dosing of a selective thromboxane A 2 (TXA 2) synthetase inhibitor, DP-1904 (DP), on prostanoid metabolism, were also studied. Urinary excretion of TXB 2, which reflects the renal production of TXA 2, was significantly increased in the patients with lupus nephritis as compared with non-renal SLE (p < 0.05). The urinary TXB 2/6-keto-PGF1α ratio was also increased in lupus nephritis as compared with non-renal SLE or healthy controls (p < 0.01), indicating a prostanoid imbalance, which may lead to impaired renal function and subsequent pathology. The urinary TXB 2/6-keto-PGF(1α) ratio in these lupus nephritis patients showed negative correlations with Ccr and positive correlations with anti-DNA antibody titer (p < 0.001). DP was administered orally (400 mg/day, given in two divided doses) for four days to eight lupus nephritis patients. The urinary excretion of TXB 2 and urinary TXB 2/6-keto-PGF1α ratio were decreased after one to two days of treatment in all patients. An increase in creatinine clearance used as a measure of renal function was observed in four of eight patients. Furthermore, no side effects were elicited during the four days of treatment. The conclusions reached were that the abnormal prostanoid metabolism observed in lupus nephritis could aggravate renal function through hemodynamic mediation, and that the deviated metabolism was reversible and, at least partially, corrected by a TXA 2 synthetase inhibitor.

Original languageEnglish
Pages (from-to)129-138
Number of pages10
JournalLupus
Volume5
Issue number2
Publication statusPublished - 1996

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Keywords

  • Lupus nephritis
  • Prostacyclin
  • Prostanoids
  • Thromboxane A
  • Thromboxane A synthetase inhibitor

ASJC Scopus subject areas

  • Rheumatology
  • Immunology

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