(hemolytic uremic syndrome; HUS) Gasser 1955 [1] [6] Shiga toxin (STX) Factor H [2] 2% 4% (de novo posttransplant HUS) [3] 50% (endstage renal (recurrent post-transplant HUS) disease; ESRD) [4] 80% STX 5% [5] (thrombotic thrombocytopenia purpura; TTP) (thrombocytopenia) (microangiopathic hemolytic anemia; MAHA) (neurologic H STX De novo post-transplant HUS calcineurin inhibitors cyclosporine A (CsA) tacrolimus abnormalities) OKT3 (schistocytes) (cytomegalovirus CMV) C (LDH) anticardiolipin antibody [7] (STX) Cyclosporine (CsA) O157 CsA H7 1981 Shulman 92 15 3 115
CsA CsA 24 1% tacrolimus CsA (uveitis) OKT3 (psoriasis) prothombin CsA TNF-α Cyclophosphamide methotrexate Zarifian 1999 188 26 CsA 2 [11] 24 0.5 mg/dl influenza A virus [8] parvoviruses cytomegalovirus Parvoviruses P- 15% antigen CsA 3 5% cytomegalovirus CsA vwf [12] CsA lactate dehydrogenase (LDH) 51 chromium ( 51 Cr) prostacyclin (total body irradiation; TBI) prostacyclin-to-thromboxane A 2 (graft versus host disease GVHD) C thromboplastin (2000 cgy) vwf multimers [9] Tacrolimus [13] Tacrolimus 1989 CsA tacrolimus [10] 1991 116 92 15 3
[16] (systemic inflammatory response syndrome SIRS) 50% 90% cytokines [13] 13 80% 90% interferon γ interleukin-1 TNF-α [17] Recurrent post-transplant HUS 1976 (50%) 51 (92%) 21 71 90 52% 9 54% (35%) (77%) 10 STX 127 159 (43%) (32%) 27% [14] STX STX [18] STX [15] STX [16-17] [17] C3 STX alternative complement pathway C3 50% 100% C3 factor H 92 15 3 117
C3 factor H Monoclonal anti-il-2 receptor antag- alternative compleonists ment pathway factor H heparin-binding capacity factor H [12] plasma C3bBb convertase cryosupernatant protein A immunoadsorption ex- changes 90% [23] factor H [18] 100% CsA tacrolimus [19] STX STX / CsA tacrolimus 50% (84%) [8] IgG CsA tacrolimus [20] CsA tacrolimus [21] mycophenolate mofetil [22] calcineurin inhibitors 1. Gasser C, Gautier E, Steck A, Siebenmann RE, Oechslin R. Hamolytisch-uramische syndrome: Bilaterale Nierenrindennekrosen bei akuten erworbenen hamolytischen Anamien Schweizerische. Med Wochenschr 1955; 85: 905-9. 2. Ruggenenti P, Noris M, Remuzzi G: Thrombotic microangiopathy, hemolytic uremic syndrome and thrombotic thrombocytopenic purpura. Kidney Int 2001; 60: 831-46. 3. Petitt RM: Thrombotic thrombocytopenic purpura; a thirty year review. Semin Thromb Hemost 1980; 6: 350-5. 4. Schieppati A, Ruggenenti P, Plata Cornejo R, et al: For the Italian Registry of hemolytic uremic syndrome: Renal function at hospital admission as a prognostic factor in adult hemolytic uremic syndrome. J Am Soc Nephrol 1992; 2: 1640-4. 5. Remuzzi G, Ruggenenti P: The hemolytic uremic syndrome. Kidney Int 1995; 47: 2-19. 6. Remuzzi G, Ruggenenti P, Bertani T: Thrombotic microangiopathy, in Renal Pathology with Clinical and Func- 118 92 15 3
tional Correlations, edited by Tisher CC, Brenner BM, Philadelphia, Lippincott 1994; pp 1154-84. 7. Baid S, Pawqual M, Williams Jr WW, et al: Renal thrombotic microangiopathy associated with anticardiolipin antibodies in hepatitis C-positive renal allograft recipients. J Am Soc Nephrol 1999; 10: 146-53. 8. Zarifian A, Meleg-Smith S, O'Donovan R, et al: Cyclosporineassociated thrombotic microangiopathy in renal allografts. Kidney Int 1999; 55: 2457-66. 9. Remuzzi G, Bertani T: Renal vascular and thrombotic effects of cyclosporine. Am J Kidney Dis 1989; 13: 261-72. 10. McCauley J, Bronsther O, Fung J, et al: Treatment of cyclosporin-induced haemolytic uraemic syndrome with FK506. Lancet 1989; 2: 1516. 11. Verburgh CA, Vermejj CG, Zijlmans JMJM, et al: Haemolytic uraemic syndrome following bone marrow transplantation. Case report and review of the literature. Nephrol Dial Transplant 1996; 11: 1332-7. 12. Hochstetler LA, Flanigan MJ, Lager DJ: Transplant-associated thrombotic microangiopathy: the role of IgG administration as initial therapy. Am J Kidney Dis 1994; 23: 444-50. 13. Talatsuka H, Takemoto Y, Yamada S, et al: Complications after bone marrow transplantation are manifestations of systemic inflammatory response syndrome. Bone Marrow Transplant 2000; 26: 419-26. 14. Doucloux D, Rebibou JM, Semhoun-Ducloux S, et al: Recurrence of hemolytic-uremic syndrome in renal transplant recipients. Transplantation 1998; 65: 1405-7. 15. Ashkenazi S, Cleary TG, Lopez E, Pickering LK: Anticytotoxin-neutralizing antibodies in immune globulin preparations: Potential use in hemolytic uremic syndrome. J Pediatr 1988; 113: 1008-14. 16. Schwarz A, Krause PH, Offermann, Keller F: Recurrent and de novo renal disease after kidney transplantation with or without cyclosporine A. Am J Kidney Dis 1991; 17: 524-31. 17. Lahlou A, Lang P, Charpentier B, GROUP COOPÉRATIF DE L'ILE-DE FRANCE (GCIF): Hemolytic uremic syndrome: Recurrence after renal transplantation. Medicine (Baltimore) 2000; 79: 90-102. 18. Noris M, Ruggenenti P, Perna A, et al: Hypocomplementemia discloses genetic predisposition to hemolytic uremic syndrome and thrombotic thrombocytopenic purpura: Role of factor H abnormalities. J Am Soc Nephrol 1999; 10: 281-93. 19. Hebert D, Mauer SM: Hemolytic uremic syndrome and transplantation, in Hemolytic Uremic Syndrome and Thrombotic Thrombocytopenic Purpura, edited by Kaplan BS, Trompeter RS, Moake JL, New York, Marcel Dekker, 1992, pp 179-86. 20. Trimarchi HM, Truong LD, Brennan S, et al: FK 506-associated thrombotic microangiopathy: Report of two cases and review of the literature. Transplantation 1999; 67: 539-44. 21. Grupp C, Schmidt F, Braun F, et al: Haemolytic uremic syndrome (HUS) during treatment with cyclosporin A after renal transplantation-is tacrolimus the answer? Nephrol Dial Transplant 1998; 13: 1629-31. 22. McGregor DO, Robson RA, Lynn KL: Hemolytic uremic syndrome in a renal transplant recipient treated by conversion to mycophenolate mofetil. Nephron 1998; 80: 365-6. 23. Zeigler ZR, Shadduck RK, Nath R, et al: Pilot study of combined cryosupernatant and protein A immunoadsorption exchange in the treatment of grade 3-4 bone marrow transplantassociated thrombotic microangiopathy. Bone Marrow Transplant 1996; 17: 81-6. 92 15 3 119