Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1985 Sep;76(3):1011–1018. doi: 10.1172/JCI112053

Functional significance of renal prostacyclin and thromboxane A2 production in patients with systemic lupus erythematosus.

C Patrono, G Ciabattoni, G Remuzzi, E Gotti, S Bombardieri, O Di Munno, G Tartarelli, G A Cinotti, B M Simonetti, A Pierucci
PMCID: PMC423972  PMID: 3900132

Abstract

We have examined the urinary excretion of stable immunoreactive eicosanoids in 23 female patients with systemic lupus erythematosus (SLE), 16 patients with chronic glomerular disease (CGD), and 20 healthy women. SLE patients had significantly higher urinary thromboxane B2 (TXB2) and prostaglandin (PG) E2 excretion and significantly lower 6-keto-PGF1 alpha than did healthy women. In contrast, CGD patients only differed from controls for having reduced 6-keto-PGF1 alpha excretion. The group of SLE patients with active renal lesions differed significantly from the group with inactive lesions for having a lower creatinine clearance and urinary 6-keto-PGF1 alpha and higher urinary TXB2. Higher urinary TXB2 excretion was associated with comparable platelet TXB2 production in whole blood, undetectable TXB2 in peripheral venous blood, and unchanged urinary excretion of 2,3-dinor-TXB2. A significant inverse correlation was found between urinary TXB2 and creatinine clearance rate (CCr). In contrast, the urinary excretion of 6-keto-PGF1 alpha showed a significant linear correlation with both CCr and para-aminohippurate clearance rate (CPAH). In four SLE and seven CGD patients, inhibition of renal cyclooxygenase activity by ibuprofen was associated with a significant reduction in urinary 6-keto-PGF1 alpha and TXB2 and in both CCr and CPAH. However, the average decrease in both clearances was 50% lower in SLE patients than in CGD patients, when fractionated by the reduction in urinary 6-keto-PGF1 alpha or PGE2 excretion. We conclude that the intrarenal synthesis of PGI2 and TXA2 is specifically altered in SLE. Such biochemical alterations are associated with changes in glomerular hemodynamics and may play a role in the progression of SLE nephropathy.

Full text

PDF
1011

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Benabe J. E., Klahr S., Hoffman M. K., Morrison A. R. Production of thromboxane A2 by the kidney in glycerol-induced acute renal failure in the rabbit. Prostaglandins. 1980 Mar;19(3):333–347. doi: 10.1016/0090-6980(80)90069-6. [DOI] [PubMed] [Google Scholar]
  2. Bombardieri S., Cattani P., Ciabattoni G., Di Munno O., Pasero G., Patrono C., Pinca E., Pugliese F. The synovial prostaglandin system in chronic inflammatory arthritis: differential effects of steroidal and nonsteroidal anti-inflammatory drugs. Br J Pharmacol. 1981 Aug;73(4):893–901. doi: 10.1111/j.1476-5381.1981.tb08743.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brenner B. M., Meyer T. W., Hostetter T. H. Dietary protein intake and the progressive nature of kidney disease: the role of hemodynamically mediated glomerular injury in the pathogenesis of progressive glomerular sclerosis in aging, renal ablation, and intrinsic renal disease. N Engl J Med. 1982 Sep 9;307(11):652–659. doi: 10.1056/NEJM198209093071104. [DOI] [PubMed] [Google Scholar]
  4. Ciabattoni G., Cinotti G. A., Pierucci A., Simonetti B. M., Manzi M., Pugliese F., Barsotti P., Pecci G., Taggi F., Patrono C. Effects of sulindac and ibuprofen in patients with chronic glomerular disease. Evidence for the dependence of renal function on prostacyclin. N Engl J Med. 1984 Feb 2;310(5):279–283. doi: 10.1056/NEJM198402023100502. [DOI] [PubMed] [Google Scholar]
  5. Ciabattoni G., Pugliese F., Cinotti G. A., Stirati G., Ronci R., Castrucci G., Pierucci A., Patrono C. Characterization of furosemide-induced activation of the renal prostaglandin system. Eur J Pharmacol. 1979 Dec 7;60(2-3):181–187. doi: 10.1016/0014-2999(79)90217-6. [DOI] [PubMed] [Google Scholar]
  6. Ciabattoni G., Pugliese F., Spaldi M., Cinotti G. A., Patrono C. Radioimmunoassay measurement of prostaglandins E2 and F2alpha in human urine. J Endocrinol Invest. 1979 Apr-Jun;2(2):173–182. doi: 10.1007/BF03349310. [DOI] [PubMed] [Google Scholar]
  7. FitzGerald G. A., Oates J. A., Hawiger J., Maas R. L., Roberts L. J., 2nd, Lawson J. A., Brash A. R. Endogenous biosynthesis of prostacyclin and thromboxane and platelet function during chronic administration of aspirin in man. J Clin Invest. 1983 Mar;71(3):676–688. doi: 10.1172/JCI110814. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. FitzGerald G. A., Pedersen A. K., Patrono C. Analysis of prostacyclin and thromboxane biosynthesis in cardiovascular disease. Circulation. 1983 Jun;67(6):1174–1177. doi: 10.1161/01.cir.67.6.1174. [DOI] [PubMed] [Google Scholar]
  9. Frölich J. C., Wilson T. W., Sweetman B. J., Smigel M., Nies A. S., Carr K., Watson J. T., Oates J. A. Urinary prostaglandins. Identification and origin. J Clin Invest. 1975 Apr;55(4):763–770. doi: 10.1172/JCI107987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gryglewski R. J., Bunting S., Moncada S., Flower R. J., Vane J. R. Arterial walls are protected against deposition of platelet thrombi by a substance (prostaglandin X) which they make from prostaglandin endoperoxides. Prostaglandins. 1976 Nov;12(5):685–713. doi: 10.1016/0090-6980(76)90047-2. [DOI] [PubMed] [Google Scholar]
  11. Hassid A., Dunn M. J. Microsomal prostaglandin biosynthesis of human kidney. J Biol Chem. 1980 Mar 25;255(6):2472–2475. [PubMed] [Google Scholar]
  12. Hirata F., del Carmine R., Nelson C. A., Axelrod J., Schiffmann E., Warabi A., De Blas A. L., Nirenberg M., Manganiello V., Vaughan M. Presence of autoantibody for phospholipase inhibitory protein, lipomodulin, in patients with rheumatic diseases. Proc Natl Acad Sci U S A. 1981 May;78(5):3190–3194. doi: 10.1073/pnas.78.5.3190. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kimberly R. P., Gill J. R., Jr, Bowden R. E., Keiser H. R., Plotz P. H. Elevated urinary prostaglandins and the effects of aspirin on renal function in lupus erythematosus. Ann Intern Med. 1978 Sep;89(3):336–341. doi: 10.7326/0003-4819-89-3-336. [DOI] [PubMed] [Google Scholar]
  14. Lianos E. A., Andres G. A., Dunn M. J. Glomerular prostaglandin and thromboxane synthesis in rat nephrotoxic serum nephritis. Effects on renal hemodynamics. J Clin Invest. 1983 Oct;72(4):1439–1448. doi: 10.1172/JCI111100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Majerus P. W. Arachidonate metabolism in vascular disorders. J Clin Invest. 1983 Nov;72(5):1521–1525. doi: 10.1172/JCI111110. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Marchesi D., Parbtani A., Frampton G., Livio M., Remuzzi G., Cameron J. S. Thrombotic tendency in systemic lupus erythematosus. Lancet. 1981 Mar 28;1(8222):719–719. doi: 10.1016/s0140-6736(81)91992-9. [DOI] [PubMed] [Google Scholar]
  17. Morrison A. R., Nishikawa K., Needleman P. Unmasking of thromboxane A2 synthesis by ureteral obstruction in the rabbit kidney. Nature. 1977 May 19;267(5608):259–260. doi: 10.1038/267259a0. [DOI] [PubMed] [Google Scholar]
  18. Okegawa T., Jonas P. E., DeSchryver K., Kawasaki A., Needleman P. Metabolic and cellular alterations underlying the exaggerated renal prostaglandin and thromboxane synthesis in ureter obstruction in rabbits. Inflammatory response involving fibroblasts and mononuclear cells. J Clin Invest. 1983 Jan;71(1):81–90. doi: 10.1172/JCI110754. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Patrignani P., Filabozzi P., Catella F., Pugliese F., Patrono C. Differential effects of dazoxiben, a selective thromboxane-synthase inhibitor, on platelet and renal prostaglandin-endoperoxide metabolism. J Pharmacol Exp Ther. 1984 Feb;228(2):472–477. [PubMed] [Google Scholar]
  20. Patrignani P., Filabozzi P., Patrono C. Selective cumulative inhibition of platelet thromboxane production by low-dose aspirin in healthy subjects. J Clin Invest. 1982 Jun;69(6):1366–1372. doi: 10.1172/JCI110576. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Patrono C., Ciabattoni G., Patrignani P., Filabozzi P., Pinca E., Satta M. A., van Dorne D., Cinotti G. A., Pugliese F., Pierucci A. Evidence for a renal origin of urinary thromboxane B2 in health and disease. Adv Prostaglandin Thromboxane Leukot Res. 1983;11:493–498. [PubMed] [Google Scholar]
  22. Patrono C., Ciabattoni G., Pinca E., Pugliese F., Castrucci G., De Salvo A., Satta M. A., Peskar B. A. Low dose aspirin and inhibition of thromboxane B2 production in healthy subjects. Thromb Res. 1980 Feb 1;17(3-4):317–327. doi: 10.1016/0049-3848(80)90066-3. [DOI] [PubMed] [Google Scholar]
  23. Patrono C., Pugliese F., Ciabattoni G., Patrignani P., Maseri A., Chierchia S., Peskar B. A., Cinotti G. A., Simonetti B. M., Pierucci A. Evidence for a direct stimulatory effect of prostacyclin on renin release in man. J Clin Invest. 1982 Jan;69(1):231–239. doi: 10.1172/JCI110435. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Roberts L. J., 2nd, Sweetman B. J., Oates J. A. Metabolism of thromboxane B2 in man. Identification of twenty urinary metabolites. J Biol Chem. 1981 Aug 25;256(16):8384–8393. [PubMed] [Google Scholar]
  25. Scharschmidt L. A., Lianos E., Dunn M. J. Arachidonate metabolites and the control of glomerular function. Fed Proc. 1983 Nov;42(14):3058–3063. [PubMed] [Google Scholar]
  26. Sraer J., Ardaillou N., Sraer J. D., Ardaillou R. In vitro prostaglandin synthesis by human glomeruli and papillae. Prostaglandins. 1982 Jun;23(6):855–864. doi: 10.1016/0090-6980(82)90129-0. [DOI] [PubMed] [Google Scholar]
  27. Tan E. M., Cohen A. S., Fries J. F., Masi A. T., McShane D. J., Rothfield N. F., Schaller J. G., Talal N., Winchester R. J. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982 Nov;25(11):1271–1277. doi: 10.1002/art.1780251101. [DOI] [PubMed] [Google Scholar]
  28. Zipser R., Myers S., Needleman P. Exaggerated prostaglandin and thromboxane synthesis in the rabbit with renal vein constriction. Circ Res. 1980 Aug;47(2):231–237. doi: 10.1161/01.res.47.2.231. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES