Improvement of renal function with a selective thromboxane A2 synthetase inhibitor, DP-1904, in lupus nephritis

Tadashi Yoshida, Hideto Kameda, Yoichi Ichikawa, Takeshi Tojo, Mitsuo Homma

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Objective. To examine abnormalities of prostanoid metabolism in lupus nephritis, which may affect renal function, and the effects of 4 day dosing of a selective thromboxane A2 (TXA2) synthetase inhibitor, DP-1904, on prostanoid metabolism. Methods. Urinary levels of various prostanoids, thromboxane B2 (TXB2), 11-dehydro-TXB2, 6-ketoprostaglandin F(1α), 2,3-dinor-6-keto-PGF(1α), and prostaglandin E2 were determined. In a randomized crossover study, 8 patients with biopsy proven lupus nephritis were given 4 days' oral administration of DP-1904 (400 mg/day bid) or indomethacin (50 mg/day bid). The effects of DP-1904 on prostanoid metabolism were studied. Results. Urinary excretion of TXB2, which reflects the renal production of TXA2, was significantly increased in patients with lupus nephritis compared with non-renal systemic lupus erythematosus (SLE) (p < 0.05); enhanced production of TXA2 was also estimated in patients with lupus nephritis. The urinary TXB2/6-keto-PGF(1α) ratio was also increased in lupus nephritis compared with non-renal SLE (p < 0.01), indicating a prostanoid imbalance that may lead to impaired renal function and subsequent pathology. During administration of DP-1904, the urinary excretion of TXB2 was significantly decreased after 1 to 2 days. An increase in creatinine clearance as a measure of renal function was observed. In contrast, during the administration of indomethacin, urinary excretion of both TXB2 and 6-keto-PGF(1α) decreased and there were no significant changes in the urinary TXB2/6-keto-PGF(1α) ratio or creatinine clearance. Hemodynamic changes were associated with a slight increase in sodium excretion, but with no change in arterial blood pressure. No side effects were elicited during the 4 days of treatments. Conclusion. The abnormal prostanoid metabolism observed in lupus nephritis could aggravate renal function, which was mediated hemodynamically, and the altered metabolism was reversible and at least partially corrected by a TXA2 synthetase inhibitor, DP-1904.

Original languageEnglish
Pages (from-to)1719-1724
Number of pages6
JournalJournal of Rheumatology
Volume23
Issue number10
Publication statusPublished - 1996

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Thromboxane-A Synthase
Thromboxane B2
Lupus Nephritis
Prostaglandins
Prostaglandins F
Kidney
Thromboxane A2
Indomethacin
Systemic Lupus Erythematosus
Creatinine
Dinoprostone
Cross-Over Studies
Oral Administration
nafagrel
Arterial Pressure
Hemodynamics
Sodium
Pathology
Biopsy

Keywords

  • lupus nephritis
  • prostanoid metabolism
  • thromboxane A synthetase inhibitor

ASJC Scopus subject areas

  • Rheumatology
  • Immunology

Cite this

Improvement of renal function with a selective thromboxane A2 synthetase inhibitor, DP-1904, in lupus nephritis. / Yoshida, Tadashi; Kameda, Hideto; Ichikawa, Yoichi; Tojo, Takeshi; Homma, Mitsuo.

In: Journal of Rheumatology, Vol. 23, No. 10, 1996, p. 1719-1724.

Research output: Contribution to journalArticle

Yoshida, Tadashi ; Kameda, Hideto ; Ichikawa, Yoichi ; Tojo, Takeshi ; Homma, Mitsuo. / Improvement of renal function with a selective thromboxane A2 synthetase inhibitor, DP-1904, in lupus nephritis. In: Journal of Rheumatology. 1996 ; Vol. 23, No. 10. pp. 1719-1724.
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abstract = "Objective. To examine abnormalities of prostanoid metabolism in lupus nephritis, which may affect renal function, and the effects of 4 day dosing of a selective thromboxane A2 (TXA2) synthetase inhibitor, DP-1904, on prostanoid metabolism. Methods. Urinary levels of various prostanoids, thromboxane B2 (TXB2), 11-dehydro-TXB2, 6-ketoprostaglandin F(1α), 2,3-dinor-6-keto-PGF(1α), and prostaglandin E2 were determined. In a randomized crossover study, 8 patients with biopsy proven lupus nephritis were given 4 days' oral administration of DP-1904 (400 mg/day bid) or indomethacin (50 mg/day bid). The effects of DP-1904 on prostanoid metabolism were studied. Results. Urinary excretion of TXB2, which reflects the renal production of TXA2, was significantly increased in patients with lupus nephritis compared with non-renal systemic lupus erythematosus (SLE) (p < 0.05); enhanced production of TXA2 was also estimated in patients with lupus nephritis. The urinary TXB2/6-keto-PGF(1α) ratio was also increased in lupus nephritis compared with non-renal SLE (p < 0.01), indicating a prostanoid imbalance that may lead to impaired renal function and subsequent pathology. During administration of DP-1904, the urinary excretion of TXB2 was significantly decreased after 1 to 2 days. An increase in creatinine clearance as a measure of renal function was observed. In contrast, during the administration of indomethacin, urinary excretion of both TXB2 and 6-keto-PGF(1α) decreased and there were no significant changes in the urinary TXB2/6-keto-PGF(1α) ratio or creatinine clearance. Hemodynamic changes were associated with a slight increase in sodium excretion, but with no change in arterial blood pressure. No side effects were elicited during the 4 days of treatments. Conclusion. The abnormal prostanoid metabolism observed in lupus nephritis could aggravate renal function, which was mediated hemodynamically, and the altered metabolism was reversible and at least partially corrected by a TXA2 synthetase inhibitor, DP-1904.",
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AU - Tojo, Takeshi

AU - Homma, Mitsuo

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N2 - Objective. To examine abnormalities of prostanoid metabolism in lupus nephritis, which may affect renal function, and the effects of 4 day dosing of a selective thromboxane A2 (TXA2) synthetase inhibitor, DP-1904, on prostanoid metabolism. Methods. Urinary levels of various prostanoids, thromboxane B2 (TXB2), 11-dehydro-TXB2, 6-ketoprostaglandin F(1α), 2,3-dinor-6-keto-PGF(1α), and prostaglandin E2 were determined. In a randomized crossover study, 8 patients with biopsy proven lupus nephritis were given 4 days' oral administration of DP-1904 (400 mg/day bid) or indomethacin (50 mg/day bid). The effects of DP-1904 on prostanoid metabolism were studied. Results. Urinary excretion of TXB2, which reflects the renal production of TXA2, was significantly increased in patients with lupus nephritis compared with non-renal systemic lupus erythematosus (SLE) (p < 0.05); enhanced production of TXA2 was also estimated in patients with lupus nephritis. The urinary TXB2/6-keto-PGF(1α) ratio was also increased in lupus nephritis compared with non-renal SLE (p < 0.01), indicating a prostanoid imbalance that may lead to impaired renal function and subsequent pathology. During administration of DP-1904, the urinary excretion of TXB2 was significantly decreased after 1 to 2 days. An increase in creatinine clearance as a measure of renal function was observed. In contrast, during the administration of indomethacin, urinary excretion of both TXB2 and 6-keto-PGF(1α) decreased and there were no significant changes in the urinary TXB2/6-keto-PGF(1α) ratio or creatinine clearance. Hemodynamic changes were associated with a slight increase in sodium excretion, but with no change in arterial blood pressure. No side effects were elicited during the 4 days of treatments. Conclusion. The abnormal prostanoid metabolism observed in lupus nephritis could aggravate renal function, which was mediated hemodynamically, and the altered metabolism was reversible and at least partially corrected by a TXA2 synthetase inhibitor, DP-1904.

AB - Objective. To examine abnormalities of prostanoid metabolism in lupus nephritis, which may affect renal function, and the effects of 4 day dosing of a selective thromboxane A2 (TXA2) synthetase inhibitor, DP-1904, on prostanoid metabolism. Methods. Urinary levels of various prostanoids, thromboxane B2 (TXB2), 11-dehydro-TXB2, 6-ketoprostaglandin F(1α), 2,3-dinor-6-keto-PGF(1α), and prostaglandin E2 were determined. In a randomized crossover study, 8 patients with biopsy proven lupus nephritis were given 4 days' oral administration of DP-1904 (400 mg/day bid) or indomethacin (50 mg/day bid). The effects of DP-1904 on prostanoid metabolism were studied. Results. Urinary excretion of TXB2, which reflects the renal production of TXA2, was significantly increased in patients with lupus nephritis compared with non-renal systemic lupus erythematosus (SLE) (p < 0.05); enhanced production of TXA2 was also estimated in patients with lupus nephritis. The urinary TXB2/6-keto-PGF(1α) ratio was also increased in lupus nephritis compared with non-renal SLE (p < 0.01), indicating a prostanoid imbalance that may lead to impaired renal function and subsequent pathology. During administration of DP-1904, the urinary excretion of TXB2 was significantly decreased after 1 to 2 days. An increase in creatinine clearance as a measure of renal function was observed. In contrast, during the administration of indomethacin, urinary excretion of both TXB2 and 6-keto-PGF(1α) decreased and there were no significant changes in the urinary TXB2/6-keto-PGF(1α) ratio or creatinine clearance. Hemodynamic changes were associated with a slight increase in sodium excretion, but with no change in arterial blood pressure. No side effects were elicited during the 4 days of treatments. Conclusion. The abnormal prostanoid metabolism observed in lupus nephritis could aggravate renal function, which was mediated hemodynamically, and the altered metabolism was reversible and at least partially corrected by a TXA2 synthetase inhibitor, DP-1904.

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