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DOI: 10.1055/s-2004-835678
Platelet Dysfunction in Renal Failure
Publication History
Publication Date:
21 October 2004 (online)
Patients with end-stage renal disease suffer from complex hemostatic disorders. Uremic patients show a bleeding diathesis that is mainly due to abnormalities of primary hemostasis; in particular, platelet dysfunction and impaired platelet-vessel wall interaction. However, despite decreased platelet function, these patients have a high prevalence of cardiovascular and thrombotic complications. Platelet dysfunction in uremic patients is partially due to uremic toxins present in circulating blood. Dialysis improves platelet abnormalities and reduces, but does not eliminate, the risk of hemorrhage. Hemodialysis can even contribute to the bleeding through the continuous platelet activation induced by the interaction between blood and artificial surfaces. Thrombocytopenia, glomerular thrombosis, and thrombi in small arteries and glomerular capillaries are common pathological features in many renal diseases. Platelets are also involved directly in the pathogenesis of glomerular diseases through a variety of mechanisms, including release of active molecules, by enhancing immune complex deposition, and by altering glomerular permeability.
KEYWORDS
Platelet - renal diseases - uremia - bleeding - thrombosis
REFERENCES
- 1 Morgagni G B. Opera Omnia. Ex Typographia Remondiniana. Venezia, Italy; 1764
- 2 Lewis J H, Zucker M B, Ferguson J H. Bleeding tendency in uremia. Blood. 1956; 11 1073-1076
- 3 Rath C E, Mailliard J A, Schreiner G E. Bleeding tendency in uremia. N Engl J Med. 1957; 257 808-811
- 4 Rosenblatt S G, Drake S, Fadem S, Welch R, Lifschitz M D. Gastrointestinal blood loss in patients with chronic renal failure. Am J Kidney Dis. 1982; 1 232-236
- 5 Moia M, Mannucci P M, Vizzotto L et al.. Improvement in the haemostatic defect of uraemia after treatment with recombinant human erythropoietin. Lancet. 1987; 2 1227-1229
- 6 Larsson S O. On coagulation and fibrinolysis in renal failure. Scand J Haematol. 1971; 15(Suppl) 1-59
- 7 Stewart J H. Platelet numbers and life span in acute and chronic renal failure. Thromb Diath Haemorrh. 1967; 17 532-542
- 8 Joist J H, Remuzzi G, Mannucci P M. Abnormal bleeding and thrombosis in renal disease. In: Colman RW, Hirsh J, Marder VJ, Salzman EW Hemostasis and Thrombosis: Basic Principles and Clinical Practice Philadelphia; J.B. Lippincott 1994: 921-935
- 9 Panicucci F, Sagripanti A, Pinori E et al.. Comprehensive study of haemostasis in chronic uremia. Nephron. 1983; 33 5-8
- 10 Willoughby M LN, Crouch S J. An investigation of the haemorrhagic tendency in renal failure. Br J Haematol. 1961; 7 315
- 11 Castaldi P A, Rozenberg M C, Stewart J H. The bleeding disorder of uremia: a qualitative platelet defect. Lancet. 1966; 2 66-69
- 12 Hakim R M, Schafer A I. Hemodialysis-associated platelet activation and thrombocytopenia. Am J Med. 1985; 78 575-580
- 13 Knudsen F, Nielsen A H, Kristensen S D. The effect of dialyzer membrane material on intradialytic changes in platelet count, platelet aggregation, circulating platelet aggregates and antithrombin III. Scand J Urol Nephrol. 1985; 19 227-232
- 14 Matsuo T, Yamada T, Yamanaehi T, Ryo R. Anticoagulant therapy with MD 805 of a hemodialysis patient with heparin-induced thrombocytopenia. Thromb Res. 1990; 58 663-666
- 15 Hall A V, Clark W F, Parbtani A. Heparin-induced thrombocytopenia in renal failure. Clin Nephrol. 1992; 38 86-89
- 16 Michalak E, Walkowiak B, Paradowski M, Cieriewski C S. The decreased circulating platelet mass and its relation to bleeding time in chronic renal failure. Thromb Haemost. 1991; 65 11-14
- 17 DiMinno G, Martinez J, McKean M L et al.. Platelet dysfunction in uremia. Multifaceted defect partially corrected by dialysis. Am J Med. 1985; 79 552-559
- 18 Eknoyan G, Brown III C H. Biochemical abnormalities of platelets in renal failure. Evidence for decreased platelet serotonin, adenosine diphosphate and Mg-dependent adenosine triphosphatase. Am J Nephrol. 1981; 1 17-23
- 19 Vlachoyannis J, Schoeppe W. Adenylate cyclase activity and cAMP content of human platelets in uremia. Eur J Clin Invest. 1982; 12 379-381
- 20 Gura V, Creter D, Levi J. Elevated thrombocyte calcium content in uremia and its correction by alpha (OH) vitamin D treatment. Nephron. 1982; 30 237-239
- 21 Ware J A, Clark B A, Smith M, Salzman E W. Abnormalities of cytoplasmic Ca2+ in platelets from patients with uremia. Blood. 1989; 73 172-176
- 22 Remuzzi G, Benigni A, Dodesini P et al.. Parathyroid hormone inhibits human platelet function. Lancet. 1981; 2 1321-1323
- 23 Benigni A, Livio M, Dodesini P et al.. Inhibition of human platelet aggregation by parathyroid hormone. Is cyclic AMP implicated?. Am J Nephrol. 1985; 5 243-247
- 24 Viganò G, Gotti E, Comberti E et al.. Hyperparathyroidism does not influence the abnormal primary haemostasis in patients with chronic renal failure. Nephrol Dial Transplant. 1989; 4 971-974
- 25 Remuzzi G, Benigni A, Dodesini P et al.. Reduced platelet thromboxane formation in uremia. Evidence for a functional cyclo-oxygenase defect. J Clin Invest. 1983; 71 762-768
- 26 Winter M, Frampton G, Bennett A, Machin S J, Cameron J S. Synthesis of thromboxane B2 in uraemia and the effects of dialysis. Thromb Res. 1983; 30 265-272
- 27 Smith M C, Dunn M J. Impaired platelet thromboxane production in renal failure. Nephron. 1981; 29 133-137
- 28 Bloom A, Greaves M, Preston F E, Brown C B. Evidence against a platelet cyclooxygenase defect in uremia subjects on chronic haemodialysis. Br J Haematol. 1986; 62 143-149
- 29 Benigni A, Boccardo P, Galbusera M et al.. Reversible activation defect of the platelet glycoprotein IIb-IIIa complex in patients with uremia. Am J Kidney Dis. 1993; 22 668-676
- 30 Mezzano D, Tagle R, Panes O et al.. Hemostatic disorder of uremia: the platelet defect, main determinant of the prolonged bleeding time, is correlated with indices of activation of coagulation and fibrinolysis. Thromb Haemost. 1996; 76 312-321
- 31 Sloand E M, Sloand J A, Prodouz K et al.. Reduction of platelet glycoprotein Ib in uraemia. Br J Haematol. 1991; 77 375-381
- 32 Gawaz M P, Dobos G, Spath M et al.. Impaired function of platelet membrane glycoprotein IIb-IIIa in end-stage renal disease. J Am Soc Nephrol. 1994; 5 36-46
- 33 Sreedhara R, Itagaki I, Hakim R M. Uremic patients have decreased shear-induced platelet aggregation mediated by decreased availability of glycoprotein IIb-IIIa receptors. Am J Kidney Dis. 1996; 27 355-364
- 34 Castillo R, Lozano T, Escolar G et al.. Defective platelet adhesion on vessel subendothelium in uremic patients. Blood. 1986; 68 337-342
- 35 Zwaginga J J, Ijsseldijk M JW, Beeser-Visser N et al.. High von Willebrand factor concentration compensates a relative adhesion defect in uremic blood. Blood. 1990; 75 1498-1508
- 36 Escolar G, Cases A, Bastida E et al.. Uremic platelets have a functional defect affecting the interaction of von Willebrand factor with glycoprotein IIb-IIIa. Blood. 1990; 76 1336-1340
- 37 Deykin D. Uremic bleeding. Kidney Int. 1983; 24 698-705
- 38 Turney J H, Woods H F, Fewell M R, Weston M J. Factor VIII complex in uremia and effects of hemodialysis. BMJ. 1981; 282 1653-1656
- 39 Livio M, Mannucci P M, Vigano G et al.. Conjugated estrogens for the management of bleeding associated with renal failure. N Engl J Med. 1986; 315 731-735
- 40 Janson P A, Jubelirer S J, Weinstein M J, Deykin D. Treatment of the bleeding tendency in uremia with cryoprecipitate. N Engl J Med. 1980; 303 1318-1322
- 41 Mannucci P M, Remuzzi G, Pusineri F et al.. Deamino-8-D-arginine vasopressin shortens the bleeding time in uremia. N Engl J Med. 1983; 308 8-12
- 42 Remuzzi G, Cavenaghi A E, Mecca G, Donati M B, de Gaetano G. Prostacyclin-like activity and bleeding in renal failure. Lancet. 1977; 2 1195-1197
- 43 Kyrle P A, Stockenhuber F, Brenner B et al.. Evidence for an increased generation of prostacyclin in the microvasculature and an impairment of platelet alpha-granule release in chronic renal failure. Thromb Haemost. 1988; 60 205-208
- 44 Silberbauer K, Sinzinger H, Winter M. Increased prostacyclin availability of vascular tissue in experimentally induced acute uremia in rats. Artery. 1978; 4 554-563
- 45 Zoja C, Vigano G, Bergamelli A et al.. Prolonged bleeding time and increased vascular prostacyclin in rats with chronic renal failure: effects of conjugated estrogens. J Lab Clin Med. 1988; 112 380-386
- 46 Defreyn G, Dauden M V, Machin S J, Vermylen J. A plasma factor in uraemia which stimulates prostacyclin release from cultured endothelial cells. Thromb Res. 1980; 19 695
- 47 Radomski M W, Palmer R M, Moncada S. An L-arginine/nitric oxide pathway present in human platelets regulates aggregation. Proc Natl Acad Sci USA. 1990; 87 5193-5197
- 48 Neri I, Marietta M, Piccinini F, Volpe A, Facchinetti F. The L-arginine-nitric oxide system regulates platelet aggregation in pregnancy. J Soc Gynecol Investig. 1998; 5 192-196
- 49 Marietta M, Facchinetti F, Neri I et al.. L-arginine infusion decreases platelet aggregation through an intraplatelet nitric oxide release. Thromb Res. 1997; 88 229-235
- 50 Noris M, Benigni A, Boccardo P et al.. Enhanced nitric oxide synthesis in uremia: implications for platelet dysfunction and dialysis hypotension. Kidney Int. 1993; 44 445-450
- 51 Noris M, Remuzzi G. Uremic bleeding: closing the circle after 30 years of controversies?. Blood. 1999; 94 2569-2574
- 52 Matsumoto A, Hirata Y, Kakoki M et al.. Increased excretion of nitric oxide in exhaled air of patients with chronic renal failure. Clin Sci. 1999; 96 67-74
- 53 Madore F, Prud’homme L, Austin J S et al.. Impact of nitric oxide on blood pressure in hemodialysis patients. Am J Kidney Dis. 1997; 30 665-671
- 54 Yokokawa K, Kohno M, Yoshikawa J. Nitric oxide mediates the cardiovascular instability of haemodialysis patients. Curr Opin Nephrol Hypertens. 1996; 5 359-363
- 55 Martensson L, Hegbrandt J, Thysell H. Generation of nitrate during dialysis as a measure of nitric oxide synthesis. Artif Organs. 1997; 21 163-167
- 56 Thuraisingham R C, Cramp H A, McMahon A C et al.. Increased superoxide and nitric oxide production results in peroxynitrite formation in uremic vasculature. J Am Soc Nephrol. 1997; 8 340A
- 57 Descamps-Latscha B, Herbelin A, Nguyen A T et al.. Balance between IL-1β, TNF-α, and their specific inhibitors in chronic renal failure and maintenance dialysis. Relationships with activation markers of T cells, B cells, and monocytes. J Immunol. 1995; 154 882-892
- 58 Pereira B JG, Dinarello C A. Production of cytokines and cytokine inhibitory proteins in patients on dialysis. Nephrol Dial Transplant. 1994; 9(suppl 2) 60-71
- 59 Rabiner S F, Molinas F. The role of phenol and phenolic acids on the thrombocytopathy and defective platelet aggregation of patients with renal failure. Am J Med. 1970; 49 346-351
- 60 Horowitz H I, Stein I M, Cohen B D, White J G. Further studies on the platelet inhibitory effect of guanidinosuccinic acid and its role in uremic bleeding. Am J Med. 1970; 49 336-345
- 61 Remuzzi G, Livio E, Marchiaro G, Mecca G, de Gaetano G. Bleeding in renal failure: Altered platelet function in chronic uraemia only partially corrected by haemodialysis. Nephron. 1978; 22 347-353
- 62 Stein I M, Cohen B D, Horowitz H I. Guanidinosuccinic acid: the “X” factor in uremic bleeding?. Clin Res. 1968; 16 397A
- 63 Horowitz H I. Uremic toxins and platelet function. Arch Intern Med. 1970; 126 823-826
- 64 Remuzzi G, Marchesi D, Livio M et al.. Altered platelet and vascular prostaglandin-generation in patients with renal failure and prolonged bleeding times. Thromb Res. 1978; 13 1007-1015
- 65 Sloand E M, Bern M M, Kaldany A. Effect on platelet function of hypoalbuminemia in peritoneal dialysis. Thromb Res. 1986; 44 419-425
- 66 Turitto V T, Weiss H J. Red blood cells: their dual role in thrombus formation. Science. 1980; 207 541-543
- 67 Gaarder A, Jonsen J, Lland S et al.. Adenosine diphosphate in red cells as a factor in the adhesiveness of human blood platelets. Nature. 1961; 192 531-532
- 68 Willems C, Stel H V, van Aken W G, Van Novrik J A. Binding and inactivation of prostacyclin (PGI2) by human erythrocytes. Br J Haematol. 1983; 54 43-52
- 69 Fernandez F, Goudable C, Sie P et al.. Low hematocrit and prolonged bleeding time in uraemic patients: effect of red cell transfusions. Br J Haematol. 1985; 59 139-148
- 70 Howard A D, Moore Jr J, Welch P G, Gouge S F. Analysis of the quantitative relationship between anemia and chronic renal failure. Am J Med Sci. 1989; 297 309-313
- 71 Viganò G, Benigni A, Mendogni D et al.. Recombinant human erythropoietin to correct uremic bleeding. Am J Kidney Dis. 1991; 18 44-49
- 72 Van Geet C, Hauglustaine D, Verresen L, Vanrusselt M, Vermylen J. Haemostatic effects of recombinant human erythropoietin in chronic haemodialysis patients. Thromb Haemost. 1989; 61 117-121
- 73 Zwaginga J J, Ijsseldijk M J, de Groot P G et al.. Treatment of uremic anemia with recombinant erythropoietin also reduces the defects in platelet adhesion and aggregation caused by uremic plasma. Thromb Haemost. 1991; 66 638-647
- 74 Minetti L. Erythropoietin treatment in renal anemia: how high should the target hematocrit be?. J Nephrol. 1997; 10 117-119
- 75 Besarab A, Bolton W K, Browne J K et al.. The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin. N Engl J Med. 1998; 339 584-590
- 76 Fass R J, Copelan E A, Brandt J T, Moeschberger M L, Ashton J J. Platelet-mediated bleeding caused by broad-spectrum penicillins. J Infect Dis. 1987; 155 1242-1248
- 77 Shattil S J, Bennett J S, McDonough M, Turnbull J. Carbenicillin and penicillin G inhibit platelet function in vitro by impairing the interaction of agonists with the platelets surface. J Clin Invest. 1980; 65 329-337
- 78 Andrassy K, Ritz E. Uremia as a cause of bleeding. Am J Nephrol. 1985; 5 313-319
- 79 Bang N, Tessler S, Heidenreich R, Marks C. Effects of moxolactan on blood coagulation and platelet function. Rev Infect Dis. 1982; 4 S546-S554
- 80 Bechtold H, Andrassy K, Jahnchen E et al.. Evidence for impaired hepatic vitamin K metabolism in patients treated with N-methyl-thiotetrazole cephalosporin. Thromb Haemost. 1984; 51 358-361
- 81 Harter H R, Burch J W, Majerus P W et al.. Prevention of thrombosis in patients on hemodialysis by low dose of aspirin. N Engl J Med. 1979; 301 577-579
- 82 Lindsay R M, Ferguson D, Prentice C R, Burton J A, McNicol G P. Reduction of thrombus formation on dialyser membranes by aspirin and RA233. Lancet. 1972; 2 1287-1290
- 83 Livio M, Benigni A, Viganò G, Mecca G, Remuzzi G. Moderate doses of aspirin and risk of bleeding in renal failure. Lancet. 1986; 1 414-416
- 84 Gaspari F, Viganò G, Orisio S et al.. Aspirin prolongs bleeding time in uremia by a mechanism distinct from platelet cyclooxygenase inhibition. J Clin Invest. 1987; 79 1788-1797
- 85 Zuckerman G R, Cornette G L, Clouse R E, Harter H R. Upper gastrointestinal bleeding in patients with chronic renal failure. Ann Intern Med. 1985; 102 588-592
- 86 Simon S L, Mills J A. Non-steroidal anti-inflammatory drugs. N Engl J Med. 1980; 302 1237-1343
- 87 Harker L A, Fuster V. Pharmacology of platelet inhibitors. J Am Coll Cardiol. 1986; 8 21B-32B
- 88 Hammel F S, Johnson G C, Collins G M. A critical appraisal of the changing approaches to vascular access for chronic dialysis. Proc Eur Dial Transplant Assoc. 1982; 19 325-330
- 89 Kaegi A, Pineo G F, Shimizu A, Trivedi H, Hirsh J, Gent M. Arteriovenous shunt thrombosis. Prevention by sulfinpyrazone. N Engl J Med. 1974; 290 304-306
- 90 Fiskerstrand C E, Thompson I W, Burnet M E, Williams P, Anderton J L. Double-blind randomized trial of the effect of ticlopidine in arteriovenous fistulas for hemodialysis. Artif Organs. 1985; 9 61-63
- 91 Avram M M. Cholesterol and lipids in renal disease. Am J Med. 1989; 87 1N-2N
- 92 Cameron J S. Coagulation and thromboembolic complications in the nephrotic syndrome. Adv Nephrol Necker Hosp. 1984; 13 75-114
- 93 Llach F. Hypercoagulability, renal vein thrombosis, and other thrombotic complications of nephrotic syndrome. Kidney Int. 1985; 28 429-439
- 94 Barnett H L. Minimal change nephrotic syndrome in children: deaths during the first 5-15 years’ observation. Report of the International Study of Kidney Disease in Children. Pediatrics. 1984; 73 497-501
- 95 Mehls O, Andrassy K, Koderisch J, Herzog U, Ritz E. Hemostasis and thromboembolism in children with nephrotic syndrome: Differences from adults. J Pediatr. 1987; 110 862-867
- 96 Kendall A G, Lohmann R C, Dossetor J B. Nephrotic syndrome. A hypercoagulable state. Arch Intern Med. 1971; 127 1021-1027
- 97 Schieppati A, Dodesini P, Benigni A et al.. The metabolism of arachidonic acid by platelets in nephrotic syndrome. Kidney Int. 1984; 25 671-676
- 98 Robert A, Olmer M, Sampol J, Gugliotta J E, Casanova P. Clinical correlation between hypercoagulability and thromboembolic phenomena. Kidney Int. 1987; 31 830-835
- 99 Andrassy K, Ritz E, Bommer J. Hypercoagulability in the nephrotic syndrome. Klin Wochenschr. 1980; 58 1029-1036
- 100 Walter E, Deppermann D, Andrassy K, Koderisch J. Platelet hyperaggregability as a consequence of the nephrotic syndrome. Thromb Res. 1981; 23 473-479
- 101 Cameron J S. Platelets in glomerular disease. Annu Rev Med. 1984; 35 175-180
- 102 Zoja C, Livio M, Benigni A, Remuzzi G. Eicosanoids and platelet activating factor as mediators of injury in renal disease. In: Remuzzi G, Rossi EC Haemostasis and the Kidney. London; Butterworths 1989: 92-104
- 103 Carruthers J A, Ralfs I, Gimlette T M, Finn R. Platelet survival in acute proliferative glomerulonephritis. Clin Sci Mol Med. 1974; 47 507-513
- 104 Clark W F, Lewis M L, Cameron J S, Parsons V. Intrarenal platelet consumption in the diffuse proliferative nephritis of systemic lupus erythematosus. Clin Sci Mol Med. 1975; 49 247-252
- 105 George C RP, Slichter S J, Quadracci L J, Striker G E, Harker L A. A kinetic evaluation of hemostasis in renal disease. N Engl J Med. 1974; 291 1111-1115
- 106 Parbtani A, Clark W F, Cameron J S. Pathogenic significance of platelet activation in lupus nephritis. Transplant Proc. 1986; 18 657-658
- 107 Kant K S, Pollak V E, Weiss M A et al.. Glomerular thrombosis in systemic lupus erythematosus: prevalence and significance. Medicine (Baltimore). 1981; 60 71-86
- 108 Heptinstall R H. Hemolytic uremic syndrome, thrombotic, thrombocytopenic purpura, and systemic sclerosis (systemic scleroderma). In: Heptinstall RH Pathology of the Kidney. Boston; Little, Brown 1992: 1163-1233
- 109 Amenta P S, Katz S M. Platelets in renal scleroderma. Arch Pathol Lab Med. 1983; 107 439-440
- 110 Porter K A. Renal transplantation. In: Heptinstall RH Pathology of the Kidney. Boston; Little, Brown 1992: 1799-1933
- 111 Heptinstall R H. Hypertension I: Essential hypertension. In: Heptinstall RH Pathology of the Kidney. Boston; Little, Brown 1992: 951-1028
- 112 Duffy J L, Cinque T, Grishman E, Churg J. Intraglomerular fibrin, platelet aggregation, and subendothelial deposits in lipoid nephrosis. J Clin Invest. 1970; 49 251-258
- 113 Nakajima M, Hewitson T D, Mathews D C, Kincaid-Smith P. Platelet-derived growth factor mesangial deposits in mesangial IgA glomerulonephritis. Nephrol Dial Transplant. 1991; 6 11-16
- 114 Duffus P, Parbtani A, Frampton G, Cameron J S. Intraglomerular localization of platelet related antigens, platelet factor 4 and β-thromboglobulin in glomerulonephritis. Clin Nephrol. 1982; 17 288-297
- 115 Camussi G. Potential role of platelet-activating factor in renal pathophysiology. Kidney Int. 1986; 29 469-477
- 116 Lianos E A, Zanglis A. Glomerular platelet-activating factor levels and origin in experimental glomerulonephritis. Kidney Int. 1990; 37 736-740
- 117 Bertani T, Livio M, Macconi D et al.. Platelet activating factor (PAF) as a mediator of injury in nephrotoxic nephritis. Kidney Int. 1987; 31 1248-1256
- 118 Yoo J, Schlondorff D, Neugarten J. Protective effects of specific platelet-activating factor receptor antagonists in experimental glomerulonephritis. J Pharmacol Exp Ther. 1991; 256 841-844
- 119 Camussi G, Tetta C, Deregitus C et al.. Platelet-activating factor (PAF) in experimentally-induced rabbit acute serum sickness: role of basophil-derived PAF in immune complex deposition. J Immunol. 1982; 128 86-94
- 120 Stahl R AK, Thaiss F, Oberle G et al.. The platelet activating factor receptor antagonist WEB 2170 improves glomerular hemodynamics and morphology in a proliferative model of mesangial cell injury. J Am Soc Nephrol. 1991; 2 37-44
- 121 Morigi M, Macconi D, Riccardi E et al.. Platelet-activating factor receptor blocking reduces proteinuria and improves survival in lupus autoimmune mice. J Pharmacol Exp Ther. 1991; 258 601-606
- 122 Macconi D, Noris M, Benfenati E et al.. Increased urinary excretion of platelet activating factor in mice with lupus nephritis. Life Sci. 1991; 48 1429-1437
- 123 Barnes J L, Levine S P, Venkatachalam M A. Binding of platelet factor four (PF 4) to glomerular polyanion. Kidney Int. 1984; 25 759-765
- 124 Tetta C, Coda R, Camussi G. Human platelet cationic proteins bind to rat glomeruli, induce loss of anionic charges and increase glomerular permeability. Agents Actions. 1985; 16 24-26
- 125 Camussi G, Tetta C, Segoloni G, Coda R, Vercellone A. Localization of neutrophil cationic proteins and loss of anionic charges in glomeruli of patients with systemic lupus erythematosus glomerulonephritis. Clin Immunol Immunopathol. 1982; 24 299-314
- 126 Barnes J L. Platelets in renal disease. In: Tetta C Immunopharmacology of the Renal System. Handbook of Immunopharmacology London; Academic Press 1993: 88-118
- 127 Abboud H E. Growth factors in glomerulonephritis. Kidney Int. 1993; 43 252-267
- 128 Shultz P J, DiCorleto P E, Silver B J, Abboud H E. Mesangial cells express PDGF mRNAs and proliferate in response to PDGF. Am J Physiol. 1988; 255 F674-F684
- 129 Silver B J, Jaffer F E, Abboud H E. Platelet-derived growth factor synthesis in mesangial cells: induction by multiple peptide mitogens. Proc Natl Acad Sci USA. 1989; 86 1056-1060
- 130 Barnes J L, Hevey K A. Glomerular mesangial cell migration. Response to platelet secretory products. Am J Pathol. 1991; 138 859-866
- 131 Taraboletti G, Morigi M, Figliuzzi M et al.. Thrombospondin induces glomerular mesangial cell adhesion and migration. Lab Invest. 1992; 67 566-571
- 132 Johnson R J, Raines E W, Floege J et al.. Inhibition of mesangial cell proliferation and matrix expansion in glomerulonephritis in the rat by antibody to platelet-derived growth factor. J Exp Med. 1992; 175 1413-1416
- 133 Gesualdo L, Pinzani M, Floriano J J et al.. Platelet-derived growth factor expression in mesangial proliferative glomerulonephritis. Lab Invest. 1991; 65 160-167
- 134 Gesualdo L, Di Paolo S, Milani S et al.. Expression of platelet-derived growth factor receptors in normal and diseased human kidney. An immunohistochemistry and in situ-hybridization study. J Clin Invest. 1994; 94 50-58
- 135 Rubin K, Tingstrom A, Hasson G K et al.. Induction of B-type receptors for platelet-derived growth factor in vascular inflammation: possible implications for development of vascular proliferative lesions. Lancet. 1988; 1 1353-1356
- 136 Fellström B, Klareskog L, Heldin C H et al.. Platelet-derived growth factor receptors in the kidney. Upregulated expressions in inflammation. Kidney Int. 1989; 36 1099-1102
- 137 Border W A, Ruoslahti E. Transforming growth factor-β in disease: the dark side of tissue repair. J Clin Invest. 1992; 90 1-7
- 138 Roberts A B, Sporn M B. The transforming growth factors-β. In: Sporn MB, Roberts AB Handbook of Experimental Pharmacology, Peptide Growth Factors and Their Receptors. Berlin; Springer 1990: 419
- 139 Border W A, Noble N A. Transforming growth factor β in tissue fibrosis. N Engl J Med. 1994; 331 1286-1292
- 140 Okuda S, Languino L R, Ruoslahti E, Border W A. Elevated expression of transforming growth factor-β and proteoglycan production in experimental glomerulonephritis. Possible role in expansion of the mesangial extracellular matrix. J Clin Invest. 1990; 86 453-462
- 141 Kincaid-Smith P. The treatment of chronic mesangiocapillary (membranoproliferative) glomerulonephritis with impaired renal function. Med J Aust. 1972; 2 587-592
- 142 Cattran D, Charron R, Cardella C. Controlled trial in mesangio-capillary glomerulonephritis (MCGN). In: Zurukzoglu W, Papadimitriou M, Sion M Eighth International Congress of Nephrology: Advances in Basic and Clinical Nephrology Basel; Karger 1981: 287 (abst)
- 143 Donadio Jr J V, Anderson C F, Mitchell III J C et al.. Membranoproliferative glomerulonephritis. A prospective clinical trial of platelet-inhibitor therapy. N Engl J Med. 1984; 310 1421-1426
- 144 McTavish D, Faulds D, Gao K L. Ticlopidine. An updated review of its pharmacology and therapeutic use in platelet-dependent disorders. Drugs. 1990; 40 238-259
- 145 Hardisty R M, Powling M J, Nokes T JC. The action of ticlopidine on human platelets. Studies on aggregation, secretion, calcium mobilization and membrane glycoproteins. Thromb Haemost. 1990; 64 150-155
- 146 Grekas D, Alivanis P, Kalekou H, Syrganis C, Tourkantonis A. Are antiplatelet agents of value in the treatment of chronic glomerular disease?. Nephrol Dial Transplant. 1987; 2 377-379
- 147 Bennett C L, Kiss J E, Weinberg P D et al.. Thrombotic thrombocytopenic purpura after stenting and ticlopidine. Lancet. 1998; 352 1036-1037
- 148 Bennett C L, Weinberg P D, Rozenberg-Ben-Dror K et al.. Thrombotic thrombocytopenic purpura associated with ticlopidine: a review of 60 cases. Ann Intern Med. 1998; 128 541-544
- 149 Moncada S, Higgs E A. Arachidonate metabolism in blood cells and the vessel wall. Clin Haematol. 1986; 15 273-292
- 150 Leaf A, Weber P C. Cardiovascular effects of ω-3 fatty acids. N Engl J Med. 1988; 318 549-557
- 151 Hamazaki T, Tateno S, Shishido H. Eicosapentaenoic and IgA nephropathy. Lancet. 1984; 1 1017-1018
- 152 Bennett W M, Walker R G, Kincaid-Smith P. Treatment of IgA nephropathy with eicosapentaenoic acid (EPA): a 2-year prospective trial. Clin Nephrol. 1989; 31 128-131
- 153 Cheng I K, Chan P C, Chan M K. The effects of fish oil dietary supplement on the progression of mesangial IgA glomerulonephritis. Nephrol Dial Transplant. 1990; 5 241-246
- 154 Pettersson E E, Rekola S, Berglund L et al.. Treatment of IgA nephropathy with omega-3-polyunsaturated fatty acids: a prospective, double-blind, randomized study. Clin Nephrol. 1994; 41 183-190
- 155 Donadio J V, Bergstralh E J, Offord K P, Spencer D C, Holley K E. A controlled trial of fish oil in IgA nephropathy. Mayo nephrology collaborative group. N Engl J Med. 1994; 331 1194-1199
- 156 Dillon J J. Fish oil therapy for IgA nephropathy: efficacy and interstudy variability. J Am Soc Nephrol. 1997; 8 1739-1744
Giuseppe RemuzziM.D. F.R.C.P.
Mario Negri Institute for Pharmacological Research, Via Gavazzeni 11
24125 Bergamo, Italy
Email: manuelap@marionegri.it