Renal and Platelet Eicosanoids in Chronic Glomerular Disease

  • Carlo Patrono
Conference paper
Part of the NATO ASI Series book series (NSSA, volume 177)


Eicosanoid is the generic term which refers to lipoxygenase and cyclooxygenase products of arachidonate metabolism. Prostaglandins (PG) and the other eicosanoids are autacoids which do not have a circulating, endocrine function but rather act in a paracrine or autocrine manner affecting cells close to or at the site of PG synthesis1. Nonsteroidal anti-inflammatory drugs (NSAD) inhibit either irreversibly (aspirin) or reversibly the cyclooxygenase enzyme which converts arachidonate to the PG-endoperoxides. Presently, no similar inhibitory agents are clinically available which inhibit the lipoxygenase enzymes converting arachidonate to leukotrienes and monohydroxy fatty acids. Although glucocorticoids can limit substrate availability through the induction of a recently characterized phospholipase A2-inhibitory protein named lipocortin, their in vivo effects on endogenous PG production are rather inconsistent.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    M.J. Dunn, Renal prostaglandins, in: “Renal endocrinology”, M.J. Dunn ed., Williams and Wilkins, Baltimore (1983).Google Scholar
  2. 2.
    D. Schlondorff, Renal prostaglandin synthesis: sites of production and specific actions of prostaglandins, Am. J. Med. 81:1 (1986).CrossRefGoogle Scholar
  3. 3.
    C. Patrono, and M.J Dunn, The clinical significance of inhibition of renal prostaglandin synthesis, Kidney Int. 32: 1 (1987).PubMedGoogle Scholar
  4. 4.
    C. Patrono, G. Ciabattoni, F. Pugliese, A. Pierucci, I.A. Blair, and G.A. FitzGerald, Estimated rate of thromboxane secretion into the circulation of normal man, J. Clin. Invest. 77:590 (1986).CrossRefGoogle Scholar
  5. 5.
    C. Patrono, G. Ciabattoni, G. Remuzzi, E. Gotti, S. Bombardieri, O. Di Munno, G. Tartarelli, G.A. Cinotti, B.M. Simonetti, and A. Pierucci, Functional significance of renal prostacyclin and thromboxane A2 production in patients with systemic lupus erythematosus. J. Clin. Invest. 76:1011 (1985).CrossRefGoogle Scholar
  6. 6.
    C. Patrono, G. Ciabattoni, E. Pinca, F. Pugliese, G. Castrucci, A. De Salvo, M.A. Satta, and B.A. Peskar, Low-dose aspirin and inhibition of thromboxane B2 production in healthy subjects, Thromb. Res. 17:317 (1980).CrossRefGoogle Scholar
  7. 7.
    M. Lebel, and J.H. Grose, Abnormal renal prostaglandin production during the evolution of chronic nephropathy. Am. J. Nephrol. 6:96 (1986).CrossRefGoogle Scholar
  8. 8.
    R.P. Kimberly, J.R. Gill jr, R.E. Bowden, H.R. Keiser, and P.H. Plotz, Elevated urinary prostaglandins and the effects of aspirin on renal function in lupus erythematosus. Ann. Intern. Med. 89:336 (1978).CrossRefGoogle Scholar
  9. 9.
    C. Patrono, A. Wennmalm, G. Ciabattoni, J. Nowak, F. Pugliese, and G.A. Cinotti, Evidence for an extrarenal origin of urinary prostaglandin E2 in healthy men, Prostaglandins 18: 623 (1979).CrossRefGoogle Scholar
  10. 10.
    G. Ciabattoni, G.A. Cinotti, A. Pierucci, B. M. Simonetti, M. Manzi, F. Pugliese, P. Barsotti, G. Pecci, F. Taggi, and C. Patrono, Effects of sulindac and ibuprofen in patients with chronic glomerular disease. Evidence for the dependence of renal function on prostacyclin, N. Engl. J. Med. 310:279(1984).CrossRefGoogle Scholar
  11. 11.
    I.W. Reimann, E. Golbs, C. Fischer, and J.C. Frolich, Influence of intravenous acetylsalicylic acid and sodium salicylate on human renal function and lithium clearance, Eur. J. Clin. Pharmacol.29:435 (1985).CrossRefGoogle Scholar
  12. 12.
    V.E. Kelley, S. Sneve, and S. Musinski, Increased renal thromboxane production in murine lupus nephritis, J. Clin. Invest. 77:252 (1986).CrossRefGoogle Scholar
  13. 13.
    P. Patrignani, P. Filabozzi, and C. Patrono, Selective cumulative inhibition of platelet thromboxane production by low-dose aspirin in healthy subjects, J. Clin. Invest. 69:1366 (1982).CrossRefGoogle Scholar
  14. 14.
    P. Kincaid-Smith, Anticoagulants are of value in the treatment of renal disese, Am. J. Kidney Dis. 3:299 (1984).CrossRefGoogle Scholar
  15. 15.
    W.A. Border, Anticoagulants are of little value in the treatment of renal disease, Am. J. Kidney Dis. 3:308 (1984).CrossRefGoogle Scholar
  16. 16.
    R. Ross, The pathogenesis of atherosclerosis. An update, N. Engl. J. Med. 314:488 (1986).CrossRefGoogle Scholar
  17. 17.
    J.P. Hayslett, Role of platelets in glomerulonephritis, N. Engl. J. Med. 310:1457 (1984).CrossRefGoogle Scholar
  18. 18.
    J.S. Cameron, Platelets in glomerular disease, Ann. Rev. Med.35:175 (1984).Google Scholar
  19. 19.
    G. Remuzzi, G. Mecca, D. Marchesi, M. Livio, G. De Gaetano, M.B. Donati, and M.J. Silver, Platelet hyperaggregability and the nephrotic syndrome, Thromb. Res. 16:345 (1979).CrossRefGoogle Scholar
  20. 20.
    K.S. Kant, V.E. Pollak, M.A. Weiss, H.I. Glueck, M.A. Miller, and E.V. Hesse, Glomerular thrombosis in systemic lupus erythematosus: prevalence and significance, Medicine, 60: 71 (1981).PubMedGoogle Scholar
  21. 21.
    A. Pierucci, B.M. Simonetti, G. Pecci, G. Mavrikakis, S. Feriozzi, G.A. Cinotti, P. Patrignani, G. Ciabattoni, and C. Patrono,Thromboxane antagonism improves renal function in lupus nephritis, N. Engl. J. Med. (in press).Google Scholar
  22. 22.
    C. Patrono, Aspirin for the prevention of coronary thrombosis: current facts and perspectives, Eur. Heart J. 7:454 (1986).CrossRefGoogle Scholar
  23. 23.
    J.V. Donadio, C.F. Anderson, J.C. Mitchell, K.E. Holley, D.M. Ilstrup, V. Fuster, and J.H. Chesebro, Membranoproliferative glomerulonephritis. A prospective clinical trial of platelet-inhibitor therapy, N. Engl. J. Med. 310:1421 (1984).CrossRefGoogle Scholar
  24. 24.
    D.C. Cattran, C.J. Cardella, J.M. Roscoe, R.C. Charron, P.C. Rance, S.M. Ritchie, and P.N. Corey, Results of a controlled drug trial in membranoproliferative glomerulonephritis, Kidney Int. 27: 436 (1985).PubMedGoogle Scholar
  25. 25.
    M.L. Purkerson, J.H. Joist, J. Yates, A. Valdes, A. Morrison, and S. Klahr, Inhibition of thromboxane synthesis ameliorates the progressive kidney disease of rats with subtotal renal ablation, Proc. Natl. Acad. Sci. USA. 82:193 (1985).CrossRefGoogle Scholar
  26. 26.
    M.L. Purkerson, J.H. Joist, J. Yates, and S. Klahr, Role of hypertension and coagulation in the progressive glomerulopathy of rats with subtotal renal ablation, Mineral Electrolyte Metab. 13: 370 (1987).Google Scholar
  27. 27.
    C. Zoja, A. Benigni, M. Livio, A. Bergamelli, S. Orisio, M. Abbate, T. Bertani, and G. Remuzzi, Selective inhibition of platelet thromboxane generation with low-dose aspirin does not protect rats with reduced renal mass from the development of progressive disease, Submitted for publication.Google Scholar
  28. 28.
    A. Brandis, G. Bianchi, E. Reale, U. Helmechen, and K. Kunn, Age-dependent glomerulosclerosis and proteinuria occurring in rats of the Milan normotensive strain and not in rats of the Milan hypertensive strain, J. Lab. Invest. 55:234 (1986).Google Scholar
  29. 29.
    F. Pugliese, P. Menè, and G.A. Cinotti, Glomerular prostaglandin and thromboxane synthesis in normotensive and hypertensive rats of the Milan strain before and after development of hypertension, J. Hypertension 4(suppl 3):S391 (1984).Google Scholar
  30. 30.
    P. Salvati, C. Ferti, L. Duzzi, R. Ferrario, N. Perico, G. Remuzzi, and G. Bianchi, Effect of thromboxane synthase inhibitor on age-dependent glomerulosclerosis in Milan normotensive rats [Abstract], 10th International Congress of Nephrology, London (1987).Google Scholar
  31. 31.
    P. Salvati, F. Pugliese, C. Ferti, L. Pierucci, R. Ferrario, and C. Patrono, Selective inhibition of glomerular thromboxane-synthase in rat models of progressive glomerulosclerosis, [Abstract], Kidney Int. (in press).Google Scholar
  32. 32.
    P. Patrignani, P. Filabozzi, F. Catella, F. Pugliese, and C. Patrono, Differential effects of dazoxiben, a selective thromboxane-synthase inhibitor, on platelet and renal prostaglandin endoperoxide metabolism, J. Pharmacol. Exp. Ther. 228:472 (1984).Google Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Carlo Patrono
    • 1
  1. 1.Department of PharmacologyCatholic University School of MedicineRomeItaly

Personalised recommendations