De novo post-transplant HUS H STX. (hemolytic uremic syndrome; HUS) [6] Shiga toxin (STX) Factor H. [2] 2% 4% (de novo posttransplant

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1 (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 H Shulman

2 CsA CsA 24 1% tacrolimus CsA (uveitis) OKT3 (psoriasis) prothombin CsA TNF-α Cyclophosphamide methotrexate Zarifian CsA 2 [11] 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]

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%) % 9 54% (35%) (77%) 10 STX (43%) (32%) 27% [14] STX STX [18] STX [15] STX [16-17] [17] C3 STX alternative complement pathway C3 50% 100% C3 factor H

4 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: Ruggenenti P, Noris M, Remuzzi G: Thrombotic microangiopathy, hemolytic uremic syndrome and thrombotic thrombocytopenic purpura. Kidney Int 2001; 60: Petitt RM: Thrombotic thrombocytopenic purpura; a thirty year review. Semin Thromb Hemost 1980; 6: 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: Remuzzi G, Ruggenenti P: The hemolytic uremic syndrome. Kidney Int 1995; 47: Remuzzi G, Ruggenenti P, Bertani T: Thrombotic microangiopathy, in Renal Pathology with Clinical and Func

5 tional Correlations, edited by Tisher CC, Brenner BM, Philadelphia, Lippincott 1994; pp 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: Zarifian A, Meleg-Smith S, O'Donovan R, et al: Cyclosporineassociated thrombotic microangiopathy in renal allografts. Kidney Int 1999; 55: Remuzzi G, Bertani T: Renal vascular and thrombotic effects of cyclosporine. Am J Kidney Dis 1989; 13: McCauley J, Bronsther O, Fung J, et al: Treatment of cyclosporin-induced haemolytic uraemic syndrome with FK506. Lancet 1989; 2: 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: Hochstetler LA, Flanigan MJ, Lager DJ: Transplant-associated thrombotic microangiopathy: the role of IgG administration as initial therapy. Am J Kidney Dis 1994; 23: 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: Doucloux D, Rebibou JM, Semhoun-Ducloux S, et al: Recurrence of hemolytic-uremic syndrome in renal transplant recipients. Transplantation 1998; 65: 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: 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: 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: 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: 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 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: 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: McGregor DO, Robson RA, Lynn KL: Hemolytic uremic syndrome in a renal transplant recipient treated by conversion to mycophenolate mofetil. Nephron 1998; 80: 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:

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