Spectrum of Complement-Mediated Thrombotic Microangiopathies: Pathogenetic Insights Identifying Novel Treatment Approaches

 

 Buy Article Permissions and Reprints

Abstract

Thrombotic microangiopathy (TMA) is a rare but severe disorder characterized by endothelial cell activation and thrombus formation. It manifests with the triad of hemolytic anemia, thrombocytopenia, and organ failure. Prompt diagnosis and treatment initiation are crucial for long-term outcome. TMA often manifests subsequent to infectious events, of which (enterohemorrhagic) Escherichia coli is the most frequently reported. TMA also occurs on the background of genetic/autoimmune defects in the complement system (atypical hemolytic uremic syndrome [aHUS]) and underlying conditions, such as pregnancy, transplantation, drugs, other glomerulopathies, vasculitides, or metabolic defects. Complement activation or defects in its regulation have now been described in an increasing number of acquired diseases with TMA. Coinciding with this expanding spectrum of complement-mediated diseases, the question arises which patients might benefit from a complement-targeted therapy. Success of therapy depends on the individual contribution of complement activation in disease pathogenesis. The advent of eculizumab, a monoclonal antibody that blocks terminal complement activation, has markedly improved outcome and quality of life in patients with aHUS. This review discusses the contribution of complement and highlights its complex interaction with inflammation, coagulation, and the endothelium. Treatment experiences focusing on eculizumab therapy are discussed in detail across the emerging spectrum of complement-mediated thrombotic microangiopathies.

• References

• 1 Tati R, Kristoffersson A-C, Ståhl A-L , et al. Complement activation associated with ADAMTS13 deficiency in human and murine thrombotic microangiopathy. J Immunol 2013; 191 (5) 2184-2193
  CrossrefPubMedGoogle Scholar
• 2 Noris M, Remuzzi G. Atypical hemolytic-uremic syndrome. N Engl J Med 2009; 361 (17) 1676-1687
  CrossrefPubMedGoogle Scholar
• 3 Tsai HM. Untying the knot of thrombotic thrombocytopenic purpura and atypical hemolytic uremic syndrome. Am J Med 2013; 126 (3) 200-209
  CrossrefPubMedGoogle Scholar
• 4 Markiewski MM, Nilsson B, Ekdahl KN, Mollnes TE, Lambris JD. Complement and coagulation: strangers or partners in crime?. Trends Immunol 2007; 28 (4) 184-192
  CrossrefPubMedGoogle Scholar
• 5 Hassenpflug WA, Budde U, Schneppenheim S, Schneppenheim R. Inherited thrombotic thrombocytopenic purpura in children. Semin Thromb Hemost 2014; 40 (4) 487-492
  Article in Thieme ConnectPubMedGoogle Scholar
• 6 Knöbl P. Inherited and acquired thrombotic thrombocytopenic purpura (TTP) in adults. Semin Thromb Hemost 2014; 40 (4) 493-502
  Article in Thieme ConnectPubMedGoogle Scholar
• 7 Scheiring J, Rosales A, Zimmerhackl LB. Clinical practice. Today's understanding of the haemolytic uraemic syndrome. Eur J Pediatr 2010; 169 (1) 7-13
  CrossrefPubMedGoogle Scholar
• 8 Würzner R, Riedl M, Rosales A, Orth-Höller D. Treatment of enterohemorrhagic Escherichia coli-induced hemolytic uremic syndrome (eHUS). Semin Thromb Hemost 2014; 40 (4) 508-516
  Article in Thieme ConnectPubMedGoogle Scholar
• 9 Loirat C, Frémeaux-Bacchi V. Atypical hemolytic uremic syndrome. Orphanet J Rare Dis 2011; 6: 60
  CrossrefPubMedGoogle Scholar
• 10 Riedl M, Orth-Höller D, Würzner R. An update on the thrombotic microangiopathies hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). Semin Thromb Hemost 2014; 40 (4) 413-415
  Article in Thieme ConnectPubMedGoogle Scholar
• 11 Gasser C, Gautier E, Steck A, Siebenmann RE, Oechslin R. Hemolytic-uremic syndrome: bilateral necrosis of the renal cortex in acute acquired hemolytic anemia [in German]. Schweiz Med Wochenschr 1955; 85 (38-39) 905-909
  PubMedGoogle Scholar
• 12 Morigi M, Galbusera M, Binda E , et al. Verotoxin-1-induced up-regulation of adhesive molecules renders microvascular endothelial cells thrombogenic at high shear stress. Blood 2001; 98 (6) 1828-1835
  CrossrefPubMedGoogle Scholar
• 13 Morigi M, Galbusera M, Gastoldi S , et al. Alternative pathway activation of complement by Shiga toxin promotes exuberant C3a formation that triggers microvascular thrombosis. J Immunol 2011; 187 (1) 172-180
  CrossrefPubMedGoogle Scholar
• 14 Renner B, Klawitter J, Goldberg R , et al. Cyclosporine induces endothelial cell release of complement-activating microparticles. J Am Soc Nephrol 2013; 24 (11) 1849-1862
  CrossrefPubMedGoogle Scholar
• 15 Nadir Y, Hoffman R, Brenner B. Drug-related thrombosis in hematologic malignancies. Rev Clin Exp Hematol 2004; 8 (1) E4
  PubMedGoogle Scholar
• 16 Carrillo-Carrasco N, Venditti CP. Combined methylmalonic acidemia and homocystinuria, cblC type. II. Complications, pathophysiology, and outcomes. J Inherit Metab Dis 2012; 35 (1) 103-114
  CrossrefPubMedGoogle Scholar
• 17 Page AV, Liles WC. Biomarkers of endothelial activation/dysfunction in infectious diseases. Virulence 2013; 4 (6) 507-516
  CrossrefPubMedGoogle Scholar
• 18 Fuquay R, Renner B, Kulik L , et al. Renal ischemia-reperfusion injury amplifies the humoral immune response. J Am Soc Nephrol 2013; 24 (7) 1063-1072
  CrossrefPubMedGoogle Scholar
• 19 Lemaire M, Frémeaux-Bacchi V, Schaefer F , et al. Recessive mutations in DGKE cause atypical hemolytic-uremic syndrome. Nat Genet 2013; 45 (5) 531-536
  CrossrefPubMedGoogle Scholar
• 20 Tsai HM. Shear stress and von Willebrand factor in health and disease. Semin Thromb Hemost 2003; 29 (5) 479-488
  Article in Thieme ConnectPubMedGoogle Scholar
• 21 Kilgore KS, Shen JP, Miller BF, Ward PA, Warren JS. Enhancement by the complement membrane attack complex of tumor necrosis factor-alpha-induced endothelial cell expression of E-selectin and ICAM-1. J Immunol 1995; 155 (3) 1434-1441
  PubMedGoogle Scholar
• 22 Albrecht EA, Chinnaiyan AM, Varambally S , et al. C5a-induced gene expression in human umbilical vein endothelial cells. Am J Pathol 2004; 164 (3) 849-859
  CrossrefPubMedGoogle Scholar
• 23 Foreman KE, Vaporciyan AA, Bonish BK , et al. C5a-induced expression of P-selectin in endothelial cells. J Clin Invest 1994; 94 (3) 1147-1155
  CrossrefPubMedGoogle Scholar
• 24 Kilgore KS, Flory CM, Miller BF, Evans VM, Warren JS. The membrane attack complex of complement induces interleukin-8 and monocyte chemoattractant protein-1 secretion from human umbilical vein endothelial cells. Am J Pathol 1996; 149 (3) 953-961
  PubMedGoogle Scholar
• 25 Fosbrink M, Niculescu F, Rus V, Shin ML, Rus H. C5b-9-induced endothelial cell proliferation and migration are dependent on Akt inactivation of forkhead transcription factor FOXO1. J Biol Chem 2006; 281 (28) 19009-19018
  CrossrefPubMedGoogle Scholar
• 26 Ota H, Fox-Talbot K, Hu W , et al. Terminal complement components mediate release of von Willebrand factor and adhesion of platelets in arteries of allografts. Transplantation 2005; 79 (3) 276-281
  CrossrefPubMedGoogle Scholar
• 27 Ståhl AL, Vaziri-Sani F, Heinen S , et al. Factor H dysfunction in patients with atypical hemolytic uremic syndrome contributes to complement deposition on platelets and their activation. Blood 2008; 111 (11) 5307-5315
  CrossrefPubMedGoogle Scholar
• 28 Noris M, Remuzzi G. Thrombotic microangiopathy after kidney transplantation. Am J Transplant 2010; 10 (7) 1517-1523
  CrossrefPubMedGoogle Scholar
• 29 Johnson S, Waters A. Is complement a culprit in infection-induced forms of haemolytic uraemic syndrome?. Immunobiology 2012; 217 (2) 235-243
  CrossrefPubMedGoogle Scholar
• 30 Sundd P, Pospieszalska MK, Ley K. Neutrophil rolling at high shear: flattening, catch bond behavior, tethers and slings. Mol Immunol 2013; 55 (1) 59-69
  CrossrefPubMedGoogle Scholar
• 31 Camous L, Roumenina L, Bigot S , et al. Complement alternative pathway acts as a positive feedback amplification of neutrophil activation. Blood 2011; 117 (4) 1340-1349
  CrossrefPubMedGoogle Scholar
• 32 Gupta AK, Joshi MB, Philippova M , et al. Activated endothelial cells induce neutrophil extracellular traps and are susceptible to NETosis-mediated cell death. FEBS Lett 2010; 584 (14) 3193-3197
  CrossrefPubMedGoogle Scholar
• 33 Yousefi S, Mihalache C, Kozlowski E, Schmid I, Simon HU. Viable neutrophils release mitochondrial DNA to form neutrophil extracellular traps. Cell Death Differ 2009; 16 (11) 1438-1444
  CrossrefPubMedGoogle Scholar
• 34 Yipp BG, Petri B, Salina D , et al. Infection-induced NETosis is a dynamic process involving neutrophil multitasking in vivo. Nat Med 2012; 18 (9) 1386-1393
  CrossrefPubMedGoogle Scholar
• 35 Yu Y, Su K. Neutrophil Extracellular Traps and Systemic Lupus Erythematosus. J Clin Cell Immunol 2013; 4: 139
  PubMedGoogle Scholar
• 36 Branzk N, Papayannopoulos V. Molecular mechanisms regulating NETosis in infection and disease. Semin Immunopathol 2013; 35 (4) 513-530
  CrossrefPubMedGoogle Scholar
• 37 Fuchs TA, Kremer Hovinga JA, Schatzberg D, Wagner DD, Lämmle B. Circulating DNA and myeloperoxidase indicate disease activity in patients with thrombotic microangiopathies. Blood 2012; 120 (6) 1157-1164
  CrossrefPubMedGoogle Scholar
• 38 O'Flynn J, Dixon KO, Faber Krol MC, Daha MR, van Kooten C. Myeloperoxidase directs properdin-mediated complement activation. J Innate Immun 2013; ; doi: 10.1159/000356980
  PubMedGoogle Scholar
• 39 Al-Mayouf SM, Sunker A, Abdwani R , et al. Loss-of-function variant in DNASE1L3 causes a familial form of systemic lupus erythematosus. Nat Genet 2011; 43 (12) 1186-1188
  CrossrefPubMedGoogle Scholar
• 40 Lee-Kirsch MA, Gong M, Chowdhury D , et al. Mutations in the gene encoding the 3′-5′ DNA exonuclease TREX1 are associated with systemic lupus erythematosus. Nat Genet 2007; 39 (9) 1065-1067
  CrossrefPubMedGoogle Scholar
• 41 Saggu G, Cortes C, Emch HN, Ramirez G, Worth RG, Ferreira VP. Identification of a novel mode of complement activation on stimulated platelets mediated by properdin and C3(H2O). J Immunol 2013; 190 (12) 6457-6467
  CrossrefPubMedGoogle Scholar
• 42 Caudrillier A, Kessenbrock K, Gilliss BM , et al. Platelets induce neutrophil extracellular traps in transfusion-related acute lung injury. J Clin Invest 2012; 122 (7) 2661-2671
  CrossrefPubMedGoogle Scholar
• 43 Krisinger MJ, Goebeler V, Lu Z , et al. Thrombin generates previously unidentified C5 products that support the terminal complement activation pathway. Blood 2012; 120 (8) 1717-1725
  CrossrefPubMedGoogle Scholar
• 44 Licht C, Pluthero FG, Li L , et al. Platelet-associated complement factor H in healthy persons and patients with atypical HUS. Blood 2009; 114 (20) 4538-4545
  CrossrefPubMedGoogle Scholar
• 45 Delvaeye M, Noris M, De Vriese A , et al. Thrombomodulin mutations in atypical hemolytic-uremic syndrome. N Engl J Med 2009; 361 (4) 345-357
  CrossrefPubMedGoogle Scholar
• 46 Bu F, Maga T, Meyer NC , et al. Comprehensive genetic analysis of complement and coagulation genes in atypical hemolytic uremic syndrome. J Am Soc Nephrol 2014; 25 (1) 55-64
  CrossrefPubMedGoogle Scholar
• 47 Feng S, Eyler SJ, Zhang Y , et al. Partial ADAMTS13 variants in atypical hemolytic uremic syndrome. Blood 2013; 122 (8) 1487-1493
  CrossrefPubMedGoogle Scholar
• 48 Walport MJ. Complement. First of two parts. N Engl J Med 2001; 344 (14) 1058-1066
  CrossrefPubMedGoogle Scholar
• 49 Walport MJ. Complement. Second of two parts. N Engl J Med 2001; 344 (15) 1140-1144
  CrossrefPubMedGoogle Scholar
• 50 Frimat M, Roumenina L, Camous L , et al. Complement activation by endothelial cells treated with inflammatory cytokines or heme, in the context of atypical hemolytic uremic syndrome. Mol Immunol 2009; 46 (14) 2849
  PubMedGoogle Scholar
• 51 Bresin E, Rurali E, Caprioli J , et al; European Working Party on Complement Genetics in Renal Diseases. Combined complement gene mutations in atypical hemolytic uremic syndrome influence clinical phenotype. J Am Soc Nephrol 2013; 24 (3) 475-486
  CrossrefPubMedGoogle Scholar
• 52 Fremeaux-Bacchi V, Fakhouri F, Garnier A , et al. Genetics and outcome of atypical hemolytic uremic syndrome: a nationwide French series comparing children and adults. Clin J Am Soc Nephrol 2013; 8 (4) 554-562
  CrossrefPubMedGoogle Scholar
• 53 Hofer J, Janecke AR, Zimmerhackl LB , et al; German-Austrian HUS Study Group. Complement factor H-related protein 1 deficiency and factor H antibodies in pediatric patients with atypical hemolytic uremic syndrome. Clin J Am Soc Nephrol 2013; 8 (3) 407-415
  CrossrefPubMedGoogle Scholar
• 54 Maga TK, Nishimura CJ, Weaver AE, Frees KL, Smith RJH. Mutations in alternative pathway complement proteins in American patients with atypical hemolytic uremic syndrome. Hum Mutat 2010; 31 (6) E1445-E1460
  CrossrefPubMedGoogle Scholar
• 55 Moore I, Strain L, Pappworth I , et al. Association of factor H autoantibodies with deletions of CFHR1, CFHR3, CFHR4, and with mutations in CFH, CFI, CD46, and C3 in patients with atypical hemolytic uremic syndrome. Blood 2010; 115 (2) 379-387
  CrossrefPubMedGoogle Scholar
• 56 Sinha A, Gulati A, Saini S , et al. Prompt plasma exchanges and immunosuppressive treatment improves the outcomes of anti-factor H autoantibody-associated hemolytic uremic syndrome in children. Kidney Int 2013; ; doi: 10.1111/j.1600-6143.2008.02297.x
  PubMedGoogle Scholar
• 57 Le Quintrec M, Lionet A, Kamar N , et al. Complement mutation-associated de novo thrombotic microangiopathy following kidney transplantation. Am J Transplant 2008; 8 (8) 1694-1701
  CrossrefPubMedGoogle Scholar
• 58 Le Quintrec M, Zuber J, Moulin B , et al. Complement genes strongly predict recurrence and graft outcome in adult renal transplant recipients with atypical hemolytic and uremic syndrome. Am J Transplant 2013; 13 (3) 663-675
  CrossrefPubMedGoogle Scholar
• 59 Noone D, Al-Matrafi J, Tinckam K , et al. Antibody mediated rejection associated with complement factor h-related protein 3/1 deficiency successfully treated with eculizumab. Am J Transplant 2012; 12 (9) 2546-2553
  CrossrefPubMedGoogle Scholar
• 60 Fakhouri F, Roumenina L, Provot F , et al. Pregnancy-associated hemolytic uremic syndrome revisited in the era of complement gene mutations. J Am Soc Nephrol 2010; 21 (5) 859-867
  CrossrefPubMedGoogle Scholar
• 61 Bouts AH, Roofthooft MTR, Salomons GS, Davin J-C. CD46-associated atypical hemolytic uremic syndrome with uncommon course caused by cblC deficiency. Pediatr Nephrol 2010; 25 (12) 2547-2548
  CrossrefPubMedGoogle Scholar
• 62 Geraghty MT, Perlman EJ, Martin LS , et al. Cobalamin C defect associated with hemolytic-uremic syndrome. J Pediatr 1992; 120 (6) 934-937
  CrossrefPubMedGoogle Scholar
• 63 Komhoff M, Roofthooft MT, Teertstra T , et al. Combined renal thrombotic microangiopathy and pulmonary arterial hypertension is caused by cobalamine C deficiency. Pediatr Nephrol 2013; 28 (8) 1374
  PubMedGoogle Scholar
• 64 Jodele S, Licht C, Goebel J , et al. Abnormalities in the alternative pathway of complement in children with hematopoietic stem cell transplant-associated thrombotic microangiopathy. Blood 2013; 122 (12) 2003-2007
  CrossrefPubMedGoogle Scholar
• 65 Jodele S, Fukuda T, Vinks A , et al. Eculizumab therapy in children with severe hematopoietic stem cell transplantation-associated thrombotic microangiopathy. Biol Blood Marrow Transplant 2014; 20 (4) 518-525
  CrossrefPubMedGoogle Scholar
• 66 Chapin J, Eyler S, Smith R, Tsai HM, Laurence J. Complement factor H mutations are present in ADAMTS13-deficient, ticlopidine-associated thrombotic microangiopathies. Blood 2013; 121 (19) 4012-4013
  CrossrefPubMedGoogle Scholar
• 67 Totina A, Iorember F, El-Dahr SS, Yosypiv IV. Atypical hemolytic-uremic syndrome in a child presenting with malignant hypertension. Clin Pediatr (Phila) 2013; 52 (2) 183-186
  CrossrefPubMedGoogle Scholar
• 68 Gilbert RD, Stanley LK, Fowler DJ, Angus EM, Hardy SA, Goodship TH. Cisplatin-induced haemolytic uraemic syndrome associated with a novel intronic mutation of CD46 treated with eculizumab. Clin Kidney J 2013; 6 (4) 421-425
  CrossrefPubMedGoogle Scholar
• 69 Song D, Wu LH, Wang FM , et al. The spectrum of renal thrombotic microangiopathy in lupus nephritis. Arthritis Res Ther 2013; 15 (1) R12
  CrossrefPubMedGoogle Scholar
• 70 El Karoui K, Hill GS, Karras A , et al. A clinicopathologic study of thrombotic microangiopathy in IgA nephropathy. J Am Soc Nephrol 2012; 23 (1) 137-148
  CrossrefPubMedGoogle Scholar
• 71 Benz K, Amann K, Dittrich K, Dötsch J. Thrombotic microangiopathy as a complication in a patient with focal segmental glomerulosclerosis. Pediatr Nephrol 2007; 22 (12) 2125-2128
  CrossrefPubMedGoogle Scholar
• 72 Bökenkamp A, Hoyer PF, Offner G, Helmchen U, Brodehl J. Recurrent haemolytic uraemic syndrome in a boy with focal and segmental glomerulosclerosis. Eur J Pediatr 1992; 151 (10) 791-792
  CrossrefPubMedGoogle Scholar
• 73 Noris M, Caprioli J, Bresin E , et al. Relative role of genetic complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype. Clin J Am Soc Nephrol 2010; 5 (10) 1844-1859
  CrossrefPubMedGoogle Scholar
• 74 Skerka C, Licht C, Mengel M , et al. Autoimmune forms of thrombotic microangiopathy and membranoproliferative glomerulonephritis: Indications for a disease spectrum and common pathogenic principles. Mol Immunol 2009; 46 (14) 2801-2807
  CrossrefPubMedGoogle Scholar
• 75 Manenti L, Signorini L, Gnappi E , et al. Outcome of renal ANCA associated vasculitis (AAV) with complement hyperactivation signs: A retrospective study. Nephrol Dial Transplant 2013; 28 (Suppl. 01) i1-i2
  CrossrefPubMedGoogle Scholar
• 76 Westwood JP, Langley K, Heelas E, Machin SJ, Scully M. Complement and cytokine response in acute thrombotic thrombocytopenic purpura. Br J Haematol 2014; 164 (6) 858-866
  CrossrefPubMedGoogle Scholar
• 77 Wu TC, Yang S, Haven S , et al. Complement activation and mortality during an acute episode of thrombotic thrombocytopenic purpura. J Thromb Haemost 2013; 11 (10) 1925-1927
  PubMedGoogle Scholar
• 78 Réti M, Farkas P, Csuka D , et al. Complement activation in thrombotic thrombocytopenic purpura. J Thromb Haemost 2012; 10 (5) 791-798
  CrossrefPubMedGoogle Scholar
• 79 Thurman JM, Marians R, Emlen W , et al. Alternative pathway of complement in children with diarrhea-associated hemolytic uremic syndrome. Clin J Am Soc Nephrol 2009; 4 (12) 1920-1924
  CrossrefPubMedGoogle Scholar
• 80 Gilbert RD, Nagra A, Haq MR. Does dysregulated complement activation contribute to haemolytic uraemic syndrome secondary to Streptococcus pneumoniae?. Med Hypotheses 2013; 81 (3) 400-403
  CrossrefPubMedGoogle Scholar
• 81 Szilágyi A, Kiss N, Bereczki C , et al. The role of complement in Streptococcus pneumoniae-associated haemolytic uraemic syndrome. Nephrol Dial Transplant 2013; 28 (9) 2237-2245
  CrossrefPubMedGoogle Scholar
• 82 Bento D, Mapril J, Rocha C , et al. Triggering of atypical hemolytic uremic syndrome by influenza A (H1N1). Ren Fail 2010; 32 (6) 753-756
  CrossrefPubMedGoogle Scholar
• 83 Berner R, Krause MF, Gordjani N , et al. Hemolytic uremic syndrome due to an altered factor H triggered by neonatal pertussis. Pediatr Nephrol 2002; 17 (3) 190-192
  CrossrefPubMedGoogle Scholar
• 84 Obando I, Camacho MS, Falcon-Neyra D, Hurtado-Mingo A, Neth O. Atypical hemolytic uremic syndrome associated with Bordetella pertussis infection. Pediatr Infect Dis J 2012; 31 (11) 1210
  PubMedGoogle Scholar
• 85 Kwon T, Belot A, Ranchin B , et al. Varicella as a trigger of atypical haemolytic uraemic syndrome associated with complement dysfunction: two cases. Nephrol Dial Transplant 2009; 24 (9) 2752-2754
  CrossrefPubMedGoogle Scholar
• 86 Hale GA, Bowman LC, Rochester RJ , et al. Hemolytic uremic syndrome after bone marrow transplantation: clinical characteristics and outcome in children. Biol Blood Marrow Transplant 2005; 11 (11) 912-920
  CrossrefPubMedGoogle Scholar
• 87 Kömhoff M, Roofthooft MT, Westra D , et al. Combined pulmonary hypertension and renal thrombotic microangiopathy in cobalamin C deficiency. Pediatrics 2013; 132 (2) e540-e544
  CrossrefPubMedGoogle Scholar
• 88 Guigonis V, Frémeaux-Bacchi V, Giraudier S , et al. Late-onset thrombocytic microangiopathy caused by cblC disease: association with a factor H mutation. Am J Kidney Dis 2005; 45 (3) 588-595
  CrossrefPubMedGoogle Scholar
• 89 Sathe KP, Mehta KP. Coexistence of atypical HUS with MPGN and ANCA associated vasculitis. Pediatr Nephrol 2013; 28 (8) 1554
  PubMedGoogle Scholar
• 90 Lorcy N, Rioux-Leclercq N, Lombard M-L, Le Pogamp P, Vigneau C. Three kidneys, two diseases, one antibody?. Nephrol Dial Transplant 2011; 26 (11) 3811-3813
  CrossrefPubMedGoogle Scholar
• 91 Brackman D, Sartz L, Leh S , et al. Thrombotic microangiopathy mimicking membranoproliferative glomerulonephritis. Nephrol Dial Transplant 2011; 26 (10) 3399-3403
  CrossrefPubMedGoogle Scholar
• 92 Schmitt R, Krmar RT, Kristoffersson A, Söderberg M, Karpman D. IgA nephropathy associated with a novel N-terminal mutation in factor H. Eur J Pediatr 2011; 170 (1) 107-110
  CrossrefPubMedGoogle Scholar
• 93 Edey M, Strain L, Ward R, Ahmed S, Thomas T, Goodship TH. Is complement factor H a susceptibility factor for IgA nephropathy?. Mol Immunol 2009; 46 (7) 1405-1408
  CrossrefPubMedGoogle Scholar
• 94 Westland R, Bodria M, Carrea A , et al. Phenotypic Expansion of DGKE-Associated Diseases. J Am Soc Nephrol 2014; ; doi: 10.1681/ASN.2013080886
  PubMedGoogle Scholar
• 95 de Córdoba SR, Hidalgo MS, Pinto S, Tortajada A. Genetics of atypical hemolytic uremic syndrome (aHUS). Semin Thromb Hemost 2014; 40 (4) 422-430
  Article in Thieme ConnectPubMedGoogle Scholar
• 96 Zuber J, Fakhouri F, Roumenina LT, Loirat C, Frémeaux-Bacchi V ; French Study Group for aHUS/C3G. Use of eculizumab for atypical haemolytic uraemic syndrome and C3 glomerulopathies. Nat Rev Nephrol 2012; 8 (11) 643-657
  CrossrefPubMedGoogle Scholar
• 97 Ariceta G, Besbas N, Johnson S , et al; European Paediatric Study Group for HUS. Guideline for the investigation and initial therapy of diarrhea-negative hemolytic uremic syndrome. Pediatr Nephrol 2009; 24 (4) 687-696
  CrossrefPubMedGoogle Scholar
• 98 Rother RP, Rollins SA, Mojcik CF, Brodsky RA, Bell L. Discovery and development of the complement inhibitor eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria. Nat Biotechnol 2007; 25 (11) 1256-1264
  CrossrefPubMedGoogle Scholar
• 99 Noris M, Mescia F, Remuzzi G. STEC-HUS, atypical HUS and TTP are all diseases of complement activation. Nat Rev Nephrol 2012; 8 (11) 622-633
  CrossrefPubMedGoogle Scholar
• 100 Hofer J, Giner T, Jözsi M. Complement factor H-antibody-associated hemolytic uremic syndrome: pathogenesis, clinical presentation, and treatment. Semin Thromb Hemost 2014; 40 (4) 431-443
  Article in Thieme ConnectPubMedGoogle Scholar
• 101 Legendre CM, Licht C, Muus P , et al. Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome. N Engl J Med 2013; 368 (23) 2169-2181
  CrossrefPubMedGoogle Scholar
• 102 Zimmerhackl LB, Hofer J, Cortina G , et al. Prophylactic eculizumab after renal transplantation in atypical hemolytic-uremic syndrome. N Engl J Med 2010; 362 (18) 1746-1748
  CrossrefPubMedGoogle Scholar
• 103 Zuber J, Le Quintrec M, Krid S , et al; French Study Group for Atypical HUS. Eculizumab for atypical hemolytic uremic syndrome recurrence in renal transplantation. Am J Transplant 2012; 12 (12) 3337-3354
  CrossrefPubMedGoogle Scholar
• 104 Simonetti G, Vilalta R, Lapeyraque AL , et al. Efficacy and safety of eculizumab treatment for atypical haemolytic uremic syndrome (aHUS) in paediatric patients: Subgroup analysis of a retrospective study. Nephrol Dial Transplant 2012; 27: ii11-ii12
  PubMedGoogle Scholar
• 105 Nathanson S, Ulinski T, Frémeaux-Bacchi V, Deschênes G. Secondary failure of plasma therapy in factor H deficiency. Pediatr Nephrol 2006; 21 (11) 1769-1771
  CrossrefPubMedGoogle Scholar
• 106 Saland J. Liver-kidney transplantation to cure atypical HUS: still an option post-eculizumab?. Pediatr Nephrol 2014; 29 (3) 329-332
  CrossrefPubMedGoogle Scholar
• 107 Houdouin V, Doit C, Mariani P , et al. A pediatric cluster of Shigella dysenteriae serotype 1 diarrhea with hemolytic uremic syndrome in 2 families from France. Clin Infect Dis 2004; 38 (9) e96-e99
  CrossrefPubMedGoogle Scholar
• 108 Delans RJ, Biuso JD, Saba SR, Ramirez G. Hemolytic uremic syndrome after Campylobacter-induced diarrhea in an adult. Arch Intern Med 1984; 144 (5) 1074-1076
  CrossrefPubMedGoogle Scholar
• 109 Ballal M, Martena S. First case report of Moraxella osloensis diarrhea in a hemolytic uremic syndrome/acute renal failure child from rural coastal India-Manipal, Karnataka. Indian J Pediatr 2013; 80 (3) 255-257
  CrossrefPubMedGoogle Scholar
• 110 Rane S, Nada R, Minz M, Sakhuja V, Joshi K. Spectrum of cytomegalovirus-induced renal pathology in renal allograft recipients. Transplant Proc 2012; 44 (3) 713-716
  CrossrefPubMedGoogle Scholar
• 111 Kossiva L, Kyriakou D, Mitsioni A, Garoufi A. Acute renal failure in a child with thrombocytopenic purpura caused by acute Epstein-Barr virus infection after treatment with anti-D immunoglobulin. Pediatr Emerg Care 2013; 29 (6) 748-750
  CrossrefPubMedGoogle Scholar
• 112 Kilonback A, Dudley J, Tizard J , et al. Acute graft dysfunction and encephalitis post renal transplant: the role of epstein-barr virus. Pediatr Nephrol 2013; 28 (8) 1525
  PubMedGoogle Scholar
• 113 Waldman M, Kopp JB. Parvovirus-B19-associated complications in renal transplant recipients. Nat Clin Pract Nephrol 2007; 3 (10) 540-550
  PubMedGoogle Scholar
• 114 Vali PS, Ismal K, Gowrishankar S, Sahay M. Renal disease in human immunodeficiency virus - Not just HIV-associated nephropathy. Indian J Nephrol 2012; 22 (2) 98-102
  CrossrefPubMedGoogle Scholar
• 115 Watanabe T. Renal complications of seasonal and pandemic influenza A virus infections. Eur J Pediatr 2013; 172 (1) 15-22
  CrossrefPubMedGoogle Scholar
• 116 Allen U, Licht C. Pandemic H1N1 influenza A infection and (atypical) HUS—more than just another trigger?. Pediatr Nephrol 2011; 26 (1) 3-5
  CrossrefPubMedGoogle Scholar
• 117 Chaturvedi S, Licht C, Langlois V. Hemolytic uremic syndrome caused by Bordetella pertussis infection. Pediatr Nephrol 2010; 25 (7) 1361-1364
  CrossrefPubMedGoogle Scholar
• 118 Godron A, Pereyre S, Monet C, Llanas B, Harambat J. Hemolytic uremic syndrome complicating Mycoplasma pneumoniae infection. Pediatr Nephrol 2013; 28 (10) 2057-2060
  CrossrefPubMedGoogle Scholar
• 119 Bergin M, Menser MA, Procopis PG, Roy LP, Shaw PJ, Stevens MM. Central nervous system toxoplasmosis and hemolytic-uremic syndrome. N Engl J Med 1987; 317 (24) 1540-1541
  PubMedGoogle Scholar
• 120 Veesenmeyer AF, Edmonson MB. Trends in US hospital stays for Streptococcus pneumoniae-associated hemolytic uremic syndrome. Pediatr Infect Dis J 2013; 32 (7) 731-735
  CrossrefPubMedGoogle Scholar
• 121 Spinale JM, Ruebner RL, Kaplan BS, Copelovitch L. Update on Streptococcus pneumoniae associated hemolytic uremic syndrome. Curr Opin Pediatr 2013; 25 (2) 203-208
  CrossrefPubMedGoogle Scholar
• 122 Smith A, Johnston C, Inverarity D, Slack M, Diggle M, Mitchell T. Investigating the role of pneumococcal neuraminidase A activity in isolates from pneumococcal haemolytic uraemic syndrome. J Med Microbiol 2013; 62 (Pt 11): 1735-1742
  CrossrefPubMedGoogle Scholar
• 123 Chapin J, Weksler B, Magro C, Laurence J. Eculizumab in the treatment of refractory idiopathic thrombotic thrombocytopenic purpura. Br J Haematol 2012; 157 (6) 772-774
  CrossrefPubMedGoogle Scholar
• 124 Surridge J, Segedin ER, Grant CC. Pertussis requiring intensive care. Arch Dis Child 2007; 92 (11) 970-975
  CrossrefPubMedGoogle Scholar
• 125 Pela I, Seracini D, Caprioli A, Castelletti F, Giammanco A. Hemolytic uremic syndrome in an infant following Bordetella pertussis infection. Eur J Clin Microbiol Infect Dis 2006; 25 (8) 515-517
  CrossrefPubMedGoogle Scholar
• 126 Waters AM, Kerecuk L, Luk D , et al. Hemolytic uremic syndrome associated with invasive pneumococcal disease: the United kingdom experience. J Pediatr 2007; 151 (2) 140-144
  CrossrefPubMedGoogle Scholar
• 127 Michael M, Elliott EJ, Ridley GF, Hodson EM, Craig JC. Interventions for haemolytic uraemic syndrome and thrombotic thrombocytopenic purpura. Cochrane Database Syst Rev 2009; (1) CD003595
  PubMedGoogle Scholar
• 128 Ardissino G, Wally Ossola M, Baffero GM, Rigotti A, Cugno M. Eculizumab for atypical hemolytic uremic syndrome in pregnancy. Obstet Gynecol 2013; 122 (2 Pt 2): 487-489
  CrossrefPubMedGoogle Scholar
• 129 Zschiedrich S, Prager EP, Kuehn EW. Successful treatment of the postpartum atypical hemolytic uremic syndrome with eculizumab. Ann Intern Med 2013; 159 (1) 76
  CrossrefPubMedGoogle Scholar
• 130 Kourouklaris A, Ioannou K, Athanasiou I, Demetriou K, Panagidou A, Zavros M. Postpartum atypical hemolytic uremic syndrome in a young adult treated with eculizumab. Nephrol Dial Transplant 2013; 28: i310-i311
  PubMedGoogle Scholar
• 131 Oyen O, Strøm EH, Midtvedt K , et al. Calcineurin inhibitor-free immunosuppression in renal allograft recipients with thrombotic microangiopathy/hemolytic uremic syndrome. Am J Transplant 2006; 6 (2) 412-418
  CrossrefPubMedGoogle Scholar
• 132 Schwimmer J, Nadasdy TA, Spitalnik PF, Kaplan KL, Zand MS. De novo thrombotic microangiopathy in renal transplant recipients: a comparison of hemolytic uremic syndrome with localized renal thrombotic microangiopathy. Am J Kidney Dis 2003; 41 (2) 471-479
  CrossrefPubMedGoogle Scholar
• 133 Barnett ANR, Hadjianastassiou VG, Shaw OJ , et al. Eculizumab for salvage in post-transplant thrombotic microangiopathy. Transpl Int 2011; 24: 153
  PubMedGoogle Scholar
• 134 Commereuc M, Karras A, Amrein C , et al. Successful treatment of acute thrombotic microangiopathy by eculizumab after combined lung and kidney transplantation. Transplantation 2013; 96 (8) e58-e59
  CrossrefPubMedGoogle Scholar
• 135 Wilson CH, Brown AL, White SA, Goodship THJ, Sheerin NS, Manas DM. Successful treatment of de novo posttransplant thrombotic microangiopathy with eculizumab. Transplantation 2011; 92 (8) e42-e43
  CrossrefPubMedGoogle Scholar
• 136 Safa K, Logan MS, Batal I, Gabardi S, Rennke HG, Abdi R. Eculizumab for drug-induced de novo post-transplantation thrombotic microangiopathy: A case report. Clin Nephrol 2014; ; doi: 10.5414/CN108163
  PubMedGoogle Scholar
• 137 González-Roncero F, Suñer M, Bernal G , et al. Eculizumab treatment of acute antibody-mediated rejection in renal transplantation: case reports. Transplant Proc 2012; 44 (9) 2690-2694
  CrossrefPubMedGoogle Scholar
• 138 Locke JE, Magro CM, Singer AL , et al. The use of antibody to complement protein C5 for salvage treatment of severe antibody-mediated rejection. Am J Transplant 2009; 9 (1) 231-235
  PubMedGoogle Scholar
• 139 Chandran S, Baxter-Lowe L, Olson JL, Tomlanovich SJ, Webber A. Eculizumab for the treatment of de novo thrombotic microangiopathy post simultaneous pancreas-kidney transplantation—a case report. Transplant Proc 2011; 43 (5) 2097-2101
  CrossrefPubMedGoogle Scholar
• 140 Ho VT, Cutler C, Carter S , et al. Blood and marrow transplant clinical trials network toxicity committee consensus summary: thrombotic microangiopathy after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2005; 11 (8) 571-575
  CrossrefPubMedGoogle Scholar
• 141 Laskin BL, Goebel J, Davies SM, Jodele S. Small vessels, big trouble in the kidneys and beyond: hematopoietic stem cell transplantation-associated thrombotic microangiopathy. Blood 2011; 118 (6) 1452-1462
  CrossrefPubMedGoogle Scholar
• 142 Worel N, Greinix HT, Leitner G , et al. ABO-incompatible allogeneic hematopoietic stem cell transplantation following reduced-intensity conditioning: close association with transplant-associated microangiopathy. Transfus Apheresis Sci 2007; 36 (3) 297-304
  CrossrefPubMedGoogle Scholar
• 143 Peffault de Latour R, Xhaard A, Fremeaux-Bacchi V , et al. Successful use of eculizumab in a patient with post-transplant thrombotic microangiopathy. Br J Haematol 2013; 161 (2) 279-280
  CrossrefPubMedGoogle Scholar
• 144 Oran B, Donato M, Aleman A , et al. Transplant-associated microangiopathy in patients receiving tacrolimus following allogeneic stem cell transplantation: risk factors and response to treatment. Biol Blood Marrow Transplant 2007; 13 (4) 469-477
  CrossrefPubMedGoogle Scholar
• 145 Brunelli SM, Meyers KEC, Guttenberg M, Kaplan P, Kaplan BS. Cobalamin C deficiency complicated by an atypical glomerulopathy. Pediatr Nephrol 2002; 17 (10) 800-803
  CrossrefPubMedGoogle Scholar
• 146 Cornec-Le Gall E, Delmas Y, De Parscau L , et al. Adult-onset eculizumab-resistant hemolytic uremic syndrome associated with cobalamin C deficiency. Am J Kidney Dis 2014; 63 (1) 119-123
  CrossrefPubMedGoogle Scholar
• 147 Deodato F, Boenzi S, Rizzo C, Dionisi-Vici C. The clinical picture of early-onset cobalamin c defect (methylmalonic aciduria and homocystinuria). Paediatr Child Health (Oxford) 2008; 18 (Suppl. 01) S57-S60
  CrossrefPubMedGoogle Scholar
• 148 Iodice FG, Di Chiara L, Boenzi S , et al. Cobalamin C defect presenting with isolated pulmonary hypertension. Pediatrics 2013; 132 (1) e248-e251
  CrossrefPubMedGoogle Scholar
• 149 Kern I, Bonafe L, Bourquin V , et al. End-stage renal failure in ayoung adult: An unusual prese ntationof late-onset cobalamin C disease. J Inherit Metab Dis 2010; 33: S33
  CrossrefPubMedGoogle Scholar
• 150 Kind T, Levy J, Lee M, Kaicker S, Nicholson JF, Kane SA. Cobalamin C disease presenting as hemolytic-uremic syndrome in the neonatal period. J Pediatr Hematol Oncol 2002; 24 (4) 327-329
  CrossrefPubMedGoogle Scholar
• 151 Labrune P, Zittoun J, Duvaltier I , et al. Haemolytic uraemic syndrome and pulmonary hypertension in a patient with methionine synthase deficiency. Eur J Pediatr 1999; 158 (9) 734-739
  CrossrefPubMedGoogle Scholar
• 152 Sharma AP, Greenberg CR, Prasad AN, Prasad C. Hemolytic uremic syndrome (HUS) secondary to cobalamin C (cblC) disorder. Pediatr Nephrol 2007; 22 (12) 2097-2103
  CrossrefPubMedGoogle Scholar
• 153 Van Hove JL, Van Damme-Lombaerts R, Grünewald S , et al. Cobalamin disorder Cbl-C presenting with late-onset thrombotic microangiopathy. Am J Med Genet 2002; 111 (2) 195-201
  CrossrefPubMedGoogle Scholar
• 154 Hamasaki K, Mimura T, Kanda H , et al. Systemic lupus erythematosus and thrombotic thrombocytopenic purpura: a case report and literature review. Clin Rheumatol 2003; 22 (4-5) 355-358
  CrossrefPubMedGoogle Scholar
• 155 Chen MH, Chen MH, Chen WS , et al. Thrombotic microangiopathy in systemic lupus erythematosus: a cohort study in North Taiwan. Rheumatology (Oxford) 2011; 50 (4) 768-775
  CrossrefPubMedGoogle Scholar
• 156 Coppo R, Amore A, Peruzzi L , et al. Eculizumab (anti C5 monoclonal antibody) in a child with therapy resistant systemic lupus erythematodes. Pediatr Nephrol 2013; 28 (8) 1373
  PubMedGoogle Scholar
• 157 Tonooka K, Ito H, Shibata T, Ozaki S. Recombinant human soluble thrombomodulin for treatment of thrombotic microangiopathy associated with lupus nephritis. J Rheumatol 2012; 39 (8) 1766-1767
  CrossrefPubMedGoogle Scholar
• 158 Lonze BE, Singer AL, Montgomery RA. Eculizumab and renal transplantation in a patient with CAPS. N Engl J Med 2010; 362 (18) 1744-1745
  CrossrefPubMedGoogle Scholar
• 159 Hadaya K, Ferrari-Lacraz S, Fumeaux D , et al. Eculizumab in acute recurrence of thrombotic microangiopathy after renal transplantation. Am J Transplant 2011; 11 (11) 2523-2527
  CrossrefPubMedGoogle Scholar
• 160 Shapira I, Andrade D, Allen SL, Salmon JE. Brief report: induction of sustained remission in recurrent catastrophic antiphospholipid syndrome via inhibition of terminal complement with eculizumab. Arthritis Rheum 2012; 64 (8) 2719-2723
  CrossrefPubMedGoogle Scholar
• 161 Canaud G, Kamar N, Anglicheau D , et al. Eculizumab improves posttransplant thrombotic microangiopathy due to antiphospholipid syndrome recurrence but fails to prevent chronic vascular changes. Am J Transplant 2013; 13 (8) 2179-2185
  CrossrefPubMedGoogle Scholar
• 162 Hirsch DJ, Jindal KK, Trillo AA. Antineutrophil cytoplasmic antibody-positive crescentic glomerulonephritis and thrombotic microangiopathy. Am J Kidney Dis 1995; 26 (2) 385-386
  CrossrefPubMedGoogle Scholar
• 163 Stefanidis I, Helmchen U, Schmitt H, Maurin N, Sieberth HG. Coincidence of haemolytic uraemic syndrome and c-ANCA-associated rapidly progressive glomerulonephritis. Nephrol Dial Transplant 1998; 13 (7) 1818-1821
  CrossrefPubMedGoogle Scholar
• 164 Cheng CL, Yeoh LY, Selvan VS, Thamboo TP. ANCA-negative Pauci-immune crescentic glomerulonephritis with thrombotic microangiopathy. Ann Acad Med Singapore 2010; 39 (10) 812-814
  PubMedGoogle Scholar
• 165 Agrawal V, Vaidya CK, Ye J , et al. Concomitant thrombotic thrombocytopenic purpura and ANCA-associated vasculitis in an adolescent. Pediatr Nephrol 2011; 26 (8) 1317-1320
  CrossrefPubMedGoogle Scholar
• 166 Ozaltin F, Li B, Rauhauser A , et al. DGKE variants cause a glomerular microangiopathy that mimics membranoproliferative GN. J Am Soc Nephrol 2013; 24 (3) 377-384
  CrossrefPubMedGoogle Scholar
• 167 Kuppachi S, Chander P, Yoo J. Membranous nephropathy and thrombotic thrombocytopenic purpura treated with rituximab. J Nephrol 2009; 22 (4) 561-564
  PubMedGoogle Scholar
• 168 McDonald DT, Roy LP. Micro-angiopathic haemolysis, thrombocytopenia and nephrotic syndrome associated with membranous nephropathy in a Vietnamese boy. Aust Paediatr J 1988; 24 (5) 311-313
  PubMedGoogle Scholar
• 169 Sekar R. Malignant hypertension with thrombotic microangiopathy. Cardiology 2013; 125 (Suppl. 02) 1-510
  PubMedGoogle Scholar
• 170 Pipili C, Pantelias K, Papaioannou N, Paraskevakou H, Grapsa E. Hemolytic-uremic syndrome, malignant hypertension and IgA nephropathy: successful treatment with plasma exchange therapy. Transfus Apheresis Sci 2012; 47 (2) 155-158
  CrossrefPubMedGoogle Scholar
• 171 Deguchi I, Uchino A, Suzuki H, Tanahashi N. Malignant hypertension with reversible brainstem hypertensive encephalopathy and thrombotic microangiopathy. J Stroke Cerebrovasc Dis 2012; 21 (8) e17-e20
  PubMedGoogle Scholar
• 172 Zotos P, Grivas D, Tsitsibis K, Toumanidis S. Malignant hypertension associated with IgA nephropathy. Intern Med J 2010; 40 (9) 668-669
  CrossrefPubMedGoogle Scholar
• 173 Li X, Zhang W, Ren H, Pan X, Chen N. Malignant hypertension complicated by acute renal failure. BMJ Case Reports 2009; ; doi:10.1136/bcr.10.2008.1116
  PubMedGoogle Scholar
• 174 Shibagaki Y, Fujita T. Thrombotic microangiopathy in malignant hypertension and hemolytic uremic syndrome (HUS)/ thrombotic thrombocytopenic purpura (TTP): can we differentiate one from the other?. Hypertens Res 2005; 28 (1) 89-95
  CrossrefPubMedGoogle Scholar
• 175 Monnens L, Drayer J, De Jong M. Malignant hypertension in a child with hemolytic-uremic syndrome treated with captopril. Acta Paediatr Scand 1981; 70 (4) 583-585
  CrossrefPubMedGoogle Scholar
• 176 Ansari A, Kansal S, Chiesa-Vottero A, Simon J. Doxorubicin induced thrombotic microangiopathy-2 case reports of this unknown association. Am J Kidney Dis 2013; 61 (4) B20
  PubMedGoogle Scholar
• 177 Al Ustwani O, Lohr J, Dy G , et al. Eculizumab therapy for gemcitabine induced hemolytic uremic syndrome: case series and concise review. J Gastrointest Oncol 2014; 5 (1) E30-E33
  PubMedGoogle Scholar
• 178 Faguer S, Huart A, Fremeaux-Bacchi V, Ribes D, Chauveau D. Eculizumab and drug-induced haemolytic-uraemic syndrome. Clinical Kidney Journal. 2013; 6 (5) 484-485
  CrossrefPubMedGoogle Scholar
• 179 Nishijima Y, Hirata H, Himeno A , et al. Drug-induced thrombotic thrombocytopenic purpura successfully treated with recombinant human soluble thrombomodulin. Intern Med 2013; 52 (10) 1111-1114
  CrossrefPubMedGoogle Scholar
• 180 Scully M, Starke R, Lee R, Mackie I, Machin S, Cohen H. Successful management of pregnancy in women with a history of thrombotic thrombocytopaenic purpura. Blood Coagul Fibrinolysis 2006; 17 (6) 459-463
  CrossrefPubMedGoogle Scholar
• 181 Fakhouri F, Vercel C, Frémeaux-Bacchi V. Obstetric nephrology: AKI and thrombotic microangiopathies in pregnancy. Clin J Am Soc Nephrol 2012; 7 (12) 2100-2106
  CrossrefPubMedGoogle Scholar
• 182 Satoskar AA, Pelletier R, Adams P , et al. De novo thrombotic microangiopathy in renal allograft biopsies-role of antibody-mediated rejection. Am J Transplant 2010; 10 (8) 1804-1811
  CrossrefPubMedGoogle Scholar
• 183 Artz MA, Steenbergen EJ, Hoitsma AJ, Monnens LA, Wetzels JF. Renal transplantation in patients with hemolytic uremic syndrome: high rate of recurrence and increased incidence of acute rejections. Transplantation 2003; 76 (5) 821-826
  CrossrefPubMedGoogle Scholar
• 184 Zoja C, Furci L, Ghilardi F, Zilio P, Benigni A, Remuzzi G. Cyclosporin-induced endothelial cell injury. Lab Invest 1986; 55 (4) 455-462
  PubMedGoogle Scholar
• 185 Caires RA, Marques ID, Repizo LP , et al. De novo thrombotic microangiopathy after kidney transplantation: clinical features, treatment, and long-term patient and graft survival. Transplant Proc 2012; 44 (8) 2388-2390
  CrossrefPubMedGoogle Scholar
• 186 Reynolds JC, Agodoa LY, Yuan CM, Abbott KC. Thrombotic microangiopathy after renal transplantation in the United States. Am J Kidney Dis 2003; 42 (5) 1058-1068
  CrossrefPubMedGoogle Scholar
• 187 Chiurchiu C, Ruggenenti P, Remuzzi G. Thrombotic microangiopathy in renal transplantation. Ann Transplant 2002; 7 (1) 28-33
  PubMedGoogle Scholar
• 188 Le Quintrec M, Lionet A, Kamar N , et al. Complement mutation-associated de novo thrombotic microangiopathy following kidney transplantation. Am J Transplant 2008; 8 (8) 1694-1701
  CrossrefPubMedGoogle Scholar
• 189 Liptak P, Ivanyi B. Primer: Histopathology of calcineurin-inhibitor toxicity in renal allografts. Nat Clin Pract Nephrol 2006; 2 (7) 398-404 , quiz 404
  CrossrefPubMedGoogle Scholar
• 190 The Canadian Multicentre Transplant Study Group. A randomized clinical trial of cyclosporine in cadaveric renal transplantation. Analysis at three years. N Engl J Med 1986; 314 (19) 1219-1225
  CrossrefPubMedGoogle Scholar
• 191 Lamoureux F, Gastinel LN, Mestre E, Marquet P, Essig M. Mapping cyclosporine-induced changes in protein secretion by renal cells using stable isotope labeling with amino acids in cell culture (SILAC). J Proteomics 2012; 75 (12) 3674-3687
  CrossrefPubMedGoogle Scholar
• 192 Murphy BF, Saunders JR, O'Bryan MK, Kirszbaum L, Walker ID, d'Apice AJ. SP-40,40 is an inhibitor of C5b-6-initiated haemolysis. Int Immunol 1989; 1 (5) 551-554
  CrossrefPubMedGoogle Scholar
• 193 Ståhl AL, Kristoffersson A, Olin AI , et al. A novel mutation in the complement regulator clusterin in recurrent hemolytic uremic syndrome. Mol Immunol 2009; 46 (11-12) 2236-2243
  CrossrefPubMedGoogle Scholar
• 194 Hwang EA, Kim HS, Ha E, Mun KC. Apoptosis in endothelial cells by cyclosporine. Transplant Proc 2012; 44 (4) 982-984
  CrossrefPubMedGoogle Scholar
• 195 de Arriba G, Calvino M, Benito S, Parra T. Cyclosporine A-induced apoptosis in renal tubular cells is related to oxidative damage and mitochondrial fission. Toxicol Lett 2013; 218 (1) 30-38
  CrossrefPubMedGoogle Scholar
• 196 Ikezoe T, Yang J, Nishioka C, Honda G, Furihata M, Yokoyama A. Thrombomodulin protects endothelial cells from a calcineurin inhibitor-induced cytotoxicity by upregulation of extracellular signal-regulated kinase/myeloid leukemia cell-1 signaling. Arterioscler Thromb Vasc Biol 2012; 32 (9) 2259-2270
  CrossrefPubMedGoogle Scholar
• 197 Cutler C, Henry NL, Magee C , et al. Sirolimus and thrombotic microangiopathy after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2005; 11 (7) 551-557
  CrossrefPubMedGoogle Scholar
• 198 Yılmaz VT, Koçak H, Avcı AB, Salim O, Ersoy FF, Süleymanlar G. Thrombotic thrombocytopenic purpura associated with everolimus use in a renal transplant patient. Int Urol Nephrol 2011; 43 (2) 581-584
  CrossrefPubMedGoogle Scholar
• 199 Meehan SM, Kremer J, Ali FN , et al. Thrombotic microangiopathy and peritubular capillary C4d expression in renal allograft biopsies. Clin J Am Soc Nephrol 2011; 6 (2) 395-403
  CrossrefPubMedGoogle Scholar
• 200 Stegall MD, Chedid MF, Cornell LD. The role of complement in antibody-mediated rejection in kidney transplantation. Nat Rev Nephrol 2012; 8 (11) 670-678
  CrossrefPubMedGoogle Scholar
• 201 Loupy A, Lefaucheur C, Vernerey D , et al. Complement-binding anti-HLA antibodies and kidney-allograft survival. N Engl J Med 2013; 369 (13) 1215-1226
  CrossrefPubMedGoogle Scholar
• 202 Stegall MD, Diwan T, Raghavaiah S , et al. Terminal complement inhibition decreases antibody-mediated rejection in sensitized renal transplant recipients. Am J Transplant 2011; 11 (11) 2405-2413
  CrossrefPubMedGoogle Scholar
• 203 Nadir Y, Brenner B. Thrombotic complications associated with stem cell transplantation. Blood Rev 2012; 26 (5) 183-187
  CrossrefPubMedGoogle Scholar
• 204 Cutler C, Henry NL, Magee C , et al. Sirolimus and thrombotic microangiopathy after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2005; 11 (7) 551-557
  CrossrefPubMedGoogle Scholar
• 205 Al-Hashmi S, Boels PJ, Zadjali F , et al. Busulphan-cyclophosphamide cause endothelial injury, remodeling of resistance arteries and enhanced expression of endothelial nitric oxide synthase. PLoS ONE 2012; 7 (1) e30897
  CrossrefPubMedGoogle Scholar
• 206 Kanamori H, Maruta A, Sasaki S , et al. Diagnostic value of hemostatic parameters in bone marrow transplant-associated thrombotic microangiopathy. Bone Marrow Transplant 1998; 21 (7) 705-709
  CrossrefPubMedGoogle Scholar
• 207 Jodele S, Laskin BL, Goebel J , et al. Does early initiation of therapeutic plasma exchange improve outcome in pediatric stem cell transplant-associated thrombotic microangiopathy?. Transfusion 2013; 53 (3) 661-667
  CrossrefPubMedGoogle Scholar
• 208 Ostronoff M, Ostronoff F, Calixto R , et al. Life-threatening hemolytic-uremic syndrome treated with rituximab in an allogeneic bone marrow transplant recipient. Bone Marrow Transplant 2007; 39 (10) 649-651
  CrossrefPubMedGoogle Scholar
• 209 Au WY, Ma ES, Lee TL , et al. Successful treatment of thrombotic microangiopathy after haematopoietic stem cell transplantation with rituximab. Br J Haematol 2007; 137 (5) 475-478
  CrossrefPubMedGoogle Scholar
• 210 Carrillo-Carrasco N, Chandler RJ, Venditti CP. Combined methylmalonic acidemia and homocystinuria, cblC type. I. Clinical presentations, diagnosis and management. J Inherit Metab Dis 2012; 35 (1) 91-102
  CrossrefPubMedGoogle Scholar
• 211 Guigonis V, Frémeaux-Bacchi V, Giraudier S , et al. Late-onset thrombocytic microangiopathy caused by cblC disease: association with a factor H mutation. Am J Kidney Dis 2005; 45 (3) 588-595
  CrossrefPubMedGoogle Scholar
• 212 Samson M, Audia S, Leguy V , et al. Haemolytic-uraemic syndrome during severe lupus nephritis: efficacy of plasma exchange. Intern Med J 2012; 42 (1) 95-98
  CrossrefPubMedGoogle Scholar
• 213 Ornstein BW, Atkinson JP, Densen P. The complement system in pediatric systemic lupus erythematosus, atypical hemolytic uremic syndrome, and complocentric membranoglomerulopathies. Curr Opin Rheumatol 2012; 24 (5) 522-529
  CrossrefPubMedGoogle Scholar
• 214 Edelbauer M, Kshirsagar S, Riedl M , et al. Markers of childhood lupus nephritis indicating disease activity. Pediatr Nephrol 2011; 26 (3) 401-410
  CrossrefPubMedGoogle Scholar
• 215 Zhao J, Wu H, Khosravi M , et al; BIOLUPUS Network; GENLES Network. Association of genetic variants in complement factor H and factor H-related genes with systemic lupus erythematosus susceptibility. PLoS Genet 2011; 7 (5) e1002079
  CrossrefPubMedGoogle Scholar
• 216 Zhao J, Kamble S, Deng Y , et al. Association of elevated c5a levels, but not the presence of anti-Cfh IgG autoantibodies, with the deletion of CFHR3 and CFHR1 in SLE. Arthritis Rheum 2012; 64: S426-S427
  PubMedGoogle Scholar
• 217 Foltyn Zadura A, Zipfel PF, Bokarewa MI , et al. Factor H autoantibodies and deletion of Complement Factor H-Related protein-1 in rheumatic diseases in comparison to atypical hemolytic uremic syndrome. Arthritis Res Ther 2012; 14 (4) R185
  CrossrefPubMedGoogle Scholar
• 218 Jönsen A, Nilsson SC, Ahlqvist E , et al. Mutations in genes encoding complement inhibitors CD46 and CFH affect the age at nephritis onset in patients with systemic lupus erythematosus. Arthritis Res Ther 2011; 13 (6) R206
  CrossrefPubMedGoogle Scholar
• 219 Levine JS, Branch DW, Rauch J. The antiphospholipid syndrome. N Engl J Med 2002; 346 (10) 752-763
  CrossrefPubMedGoogle Scholar
• 220 Rangel ML, Alghamdi I, Contreras G , et al. Catastrophic antiphospholipid syndrome with concurrent thrombotic and hemorrhagic manifestations. Lupus 2013; 22 (8) 855-864
  CrossrefPubMedGoogle Scholar
• 221 Kallenberg CG, Stegeman CA, Abdulahad WH, Heeringa P. Pathogenesis of ANCA-associated vasculitis: new possibilities for intervention. Am J Kidney Dis 2013; 62 (6) 1176-1187
  CrossrefPubMedGoogle Scholar
• 222 Van Timmeren MM, Chen M, Heeringa P. Review article: Pathogenic role of complement activation in anti-neutrophil cytoplasmic auto-antibody-associated vasculitis. Nephrology (Carlton) 2009; 14 (1) 16-25
  CrossrefPubMedGoogle Scholar
• 223 Kallenberg CG, Heeringa P. Complement is crucial in the pathogenesis of ANCA-associated vasculitis. Kidney Int 2013; 83 (1) 16-18
  CrossrefPubMedGoogle Scholar
• 224 Xiao H, Schreiber A, Heeringa P, Falk RJ, Jennette JC. Alternative complement pathway in the pathogenesis of disease mediated by anti-neutrophil cytoplasmic autoantibodies. Am J Pathol 2007; 170 (1) 52-64
  CrossrefPubMedGoogle Scholar
• 225 Xiao H, Dairaghi DJ, Powers JP , et al. C5a receptor (CD88) blockade protects against MPO-ANCA GN. J Am Soc Nephrol 2014; 25 (2) 225-231
  CrossrefPubMedGoogle Scholar
• 226 Xing GQ, Chen M, Liu G , et al. Complement activation is involved in renal damage in human antineutrophil cytoplasmic autoantibody associated pauci-immune vasculitis. J Clin Immunol 2009; 29 (3) 282-291
  CrossrefPubMedGoogle Scholar
• 227 Gou SJ, Yuan J, Chen M, Yu F, Zhao MH. Circulating complement activation in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis. Kidney Int 2013; 83 (1) 129-137
  CrossrefPubMedGoogle Scholar
• 228 Twilt M, Benseler S, Cabral D. Granulomatosis with polyangiitis in childhood. Curr Rheumatol Rep 2012; 14 (2) 107-115
  CrossrefPubMedGoogle Scholar
• 229 Furuta S, Jayne D. Emerging therapies in antineutrophil cytoplasm antibody-associated vasculitis. Curr Opin Rheumatol 2014; 26 (1) 1-6
  CrossrefPubMedGoogle Scholar
• 230 Pickering MC, Cook HT. Translational mini-review series on complement factor H: renal diseases associated with complement factor H: novel insights from humans and animals. Clin Exp Immunol 2008; 151 (2) 210-230
  CrossrefPubMedGoogle Scholar
• 231 Radhakrishnan S, Lunn A, Kirschfink M , et al. Eculizumab and refractory membranoproliferative glomerulonephritis. N Engl J Med 2012; 366 (12) 1165-1166
  CrossrefPubMedGoogle Scholar
• 232 Vivarelli M, Emma F. Treatment of C3 glomerulopathy with complement blockers. Semin Thromb Hemost 2014; 40 (4) 472-477
  Article in Thieme ConnectPubMedGoogle Scholar
• 233 Pickering MC, D'Agati VD, Nester CM , et al. C3 glomerulopathy: consensus report. Kidney Int 2013; 84 (6) 1079-1089
  CrossrefPubMedGoogle Scholar
• 234 Gharavi AG, Kiryluk K, Choi M , et al. Genome-wide association study identifies susceptibility loci for IgA nephropathy. Nat Genet 2011; 43 (4) 321-327
  CrossrefPubMedGoogle Scholar
• 235 Fukuda K, Shimizu A, Kaneko T , et al. A case of secondary focal segmental glomerulosclerosis associated with malignant hypertension. CEN Case Reports. 2013; 2 (1) 68-75
  CrossrefPubMedGoogle Scholar
• 236 Caldas MLR, Menezes PA, Ramos AP. Focal segmental glomerulosclerosis de novo and cast nephropathy induced by sirolimus in a transplant patient. Histopathology 2010; 57: 237-238
  PubMedGoogle Scholar
• 237 Costero O, Picazo ML, Zamora P, Romero S, Martinez-Ara J, Selgas R. Inhibition of tyrosine kinases by sunitinib associated with focal segmental glomerulosclerosis lesion in addition to thrombotic microangiopathy. Nephrol Dial Transplant 2010; 25 (3) 1001-1003
  CrossrefPubMedGoogle Scholar
• 238 Glassock RJ. Pathogenesis of membranous nephropathy: a new paradigm in evolution. Contrib Nephrol 2013; 181: 131-142
  PubMedGoogle Scholar
• 239 Van Den Born B, Van Der Hoeven N, Owenberg EL , et al. Endothelial damage, platelet activation, thrombin generation and fibrinolytic activity in patients with hypertensive crisis. J Hypertens 2011; 29: 922-927
  CrossrefPubMedGoogle Scholar
• 240 van den Born BJ, van der Hoeven NV, Groot E , et al. Association between thrombotic microangiopathy and reduced ADAMTS13 activity in malignant hypertension. Hypertension 2008; 51 (4) 862-866
  CrossrefPubMedGoogle Scholar
• 241 Higashi Y, Kihara Y, Noma K. Endothelial dysfunction and hypertension in aging. Hypertens Res 2012; 35 (11) 1039-1047
  CrossrefPubMedGoogle Scholar
• 242 Thachil J. The malignant hypertension-thrombotic microangiopathy link. Hypertension 2008; 52 (4) e32 , author reply e33
  CrossrefPubMedGoogle Scholar
• 243 Klinger JR, Abman SH, Gladwin MT. Nitric oxide deficiency and endothelial dysfunction in pulmonary arterial hypertension. Am J Respir Crit Care Med 2013; 188 (6) 639-646
  CrossrefPubMedGoogle Scholar
• 244 van den Born BJ, Honnebier UP, Koopmans RP, van Montfrans GA. Microangiopathic hemolysis and renal failure in malignant hypertension. Hypertension 2005; 45 (2) 246-251
  CrossrefPubMedGoogle Scholar
• 245 Frimat M, Tabarin F, Dimitrov JD , et al. Complement activation by heme as a secondary hit for atypical hemolytic uremic syndrome. Blood 2013; 122 (2) 282-292
  CrossrefPubMedGoogle Scholar
• 246 Hill A, Rother RP, Wang X , et al. Effect of eculizumab on haemolysis-associated nitric oxide depletion, dyspnoea, and measures of pulmonary hypertension in patients with paroxysmal nocturnal haemoglobinuria. Br J Haematol 2010; 149 (3) 414-425
  CrossrefPubMedGoogle Scholar
• 247 George JN, Terrell DR, Vesely SK, Kremer Hovinga JA, Lämmle B. Thrombotic microangiopathic syndromes associated with drugs, HIV infection, hematopoietic stem cell transplantation and cancer. Presse Med 2012; 41 (3 Pt 2): e177-e188
  CrossrefPubMedGoogle Scholar
• 248 Kreuter J, Winters JL. Drug-associated thrombotic microangiopathies. Semin Thromb Hemost 2012; 38 (8) 839-844
  Article in Thieme ConnectPubMedGoogle Scholar
• 249 Eremina V, Jefferson JA, Kowalewska J , et al. VEGF inhibition and renal thrombotic microangiopathy. N Engl J Med 2008; 358 (11) 1129-1136
  CrossrefPubMedGoogle Scholar
• 250 Gu X, Herrera GA. Thrombotic microangiopathy in cocaine abuse-associated malignant hypertension: report of 2 cases with review of the literature. Arch Pathol Lab Med 2007; 131 (12) 1817-1820
  PubMedGoogle Scholar
• 251 Volcy J, Nzerue CM, Oderinde A, Hewan-Iowe K. Cocaine-induced acute renal failure, hemolysis, and thrombocytopenia mimicking thrombotic thrombocytopenic purpura. Am J Kidney Dis 2000; 35 (1) E3
  CrossrefPubMedGoogle Scholar
• 252 Park YA, Hay SN, King KE , et al. Is it quinine TTP/HUS or quinine TMA? ADAMTS13 levels and implications for therapy. J Clin Apher 2009; 24 (3) 115-119
  CrossrefPubMedGoogle Scholar
• 253 Eremina V, Quaggin SE. Biology of anti-angiogenic therapy-induced thrombotic microangiopathy. Semin Nephrol 2010; 30 (6) 582-590
  CrossrefPubMedGoogle Scholar
• 254 Nwaba A, MacQuillan G, Adams LA , et al. Tacrolimus-induced thrombotic microangiopathy in orthotopic liver transplant patients: case series of four patients. Intern Med J 2013; 43 (3) 328-333
  CrossrefPubMedGoogle Scholar
• 255 Crum NF, Gable P. Quinine-induced hemolytic-uremic syndrome. South Med J 2000; 93 (7) 726-728
  CrossrefPubMedGoogle Scholar