Plasmatherapy in Atypical Hemolytic Uremic Syndrome

ABSTRACT

Plasmatherapy has become empirically first-line treatment in atypical hemolytic uremic syndrome (aHUS), although no prospective controlled trials have been conducted. Patients with mutations that induce complete or partial factor H (FH) quantitative deficiency may be controlled by plasma infusions (PI), but plasma exchanges appear more efficient than PI in patients with mutations that result in a mutant dysfunctional FH in the circulation. Early treatment is crucial. Long-term prophylactic plasmatherapy appears more efficient to prevent end-stage renal disease (ESRD) than plasmatherapy only during relapses. However, the longest follow-up with preserved renal function under plasmatherapy is only 6.5 years. Plasmatherapy does not appear to influence the outcome of aHUS with membrane cofactor protein mutation, and its efficacy in patients with factor I, C3, or factor B mutations is suggested by a few reports. We hope complement blockers will offer patients a better chance to avoid ESRD and provide a better quality of life.

KEYWORDS

Atypical hemolytic uremic syndrome - plasma infusions - plasma exchange - complement

REFERENCES

• 1 Noris M, Remuzzi G. Atypical hemolytic-uremic syndrome.  N Engl J Med. 2009;  361(17) 1676-1687
• 2 Caprioli J, Noris M, Brioschi S International Registry of Recurrent and Familial HUS/TTP et al. Genetics of HUS: the impact of MCP, CFH, and IF mutations on clinical presentation, response to treatment, and outcome.  Blood. 2006;  108(4) 1267-1279
• 3 Sellier-Leclerc A L, Freméaux-Bacchi V, Dragon-Durey M A French Society of Pediatric Nephrology et al. Differential impact of complement mutations on clinical characteristics in atypical hemolytic uremic syndrome.  J Am Soc Nephrol. 2007;  18(8) 2392-2400
• 4 Loirat C, Noris M, Frémeaux-Bacchi V. Complement and the atypical hemolytic uremic syndrome in children.  Pediatr Nephrol. 2008;  23(11) 1957-1972
• 5 Byrnes J J, Khurana M. Treatment of thrombotic thrombocytopenic purpura with plasma.  N Engl J Med. 1977;  297(25) 1386-1389
• 6 Bukowski R M, King J W, Hewlett J S. Plasmapheresis in the treatment of thrombotic thrombocytopenic purpura.  Blood. 1977;  50(3) 413-417
• 7 Bell W R, Braine H G, Ness P M, Kickler T S. Improved survival in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Clinical experience in 108 patients.  N Engl J Med. 1991;  325(6) 398-403
• 8 Rock G A, Shumak K H, Buskard N A Canadian Apheresis Study Group et al. Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura.  N Engl J Med. 1991;  325(6) 393-397
• 9 Rizzoni G, Claris-Appiani A, Edefonti A et al. Plasma infusion for hemolytic-uremic syndrome in children: results of a multicenter controlled trial.  J Pediatr. 1988;  112(2) 284-290
• 10 Loirat C, Sonsino E, Hinglais N, Jais J P, Landais P, Fermanian J. The French Society of Paediatric Nephrology . Treatment of the childhood haemolytic uraemic syndrome with plasma. A multicentre randomized controlled trial.  Pediatr Nephrol. 1988;  2(3) 279-285
• 11 Michael M, Elliott E J, Craig J C, Ridley G, Hodson E M. Interventions for hemolytic uremic syndrome and thrombotic thrombocytopenic purpura: a systematic review of randomized controlled trials.  Am J Kidney Dis. 2009;  53(2) 259-272
• 12 Noris M, Remuzzi G. Thrombotic microangiopathy: what not to learn from a meta-analysis.  Nat Rev Nephrol. 2009;  5(4) 186-188
• 13 Gianviti A, Perna A, Caringella A et al. Plasma exchange in children with hemolytic-uremic syndrome at risk of poor outcome.  Am J Kidney Dis. 1993;  22(2) 264-266
• 14 Ruggenenti P, Remuzzi G. Pathophysiology and management of thrombotic microangiopathies.  J Nephrol. 1998;  11(6) 300-310
• 15 Eddy A A, Geary D F, Balfe J W, Clark W F, Baumal R. Prolongation of acute renal failure in two patients with hemolytic-uremic syndrome due to excessive plasma infusion therapy.  Pediatr Nephrol. 1989;  3(4) 420-423
• 16 Filler G, Radhakrishnan S, Strain L, Hill A, Knoll G, Goodship T H. Challenges in the management of infantile factor H associated hemolytic uremic syndrome.  Pediatr Nephrol. 2004;  19(8) 908-911
• 17 Saunders R E, Abarrategui-Garrido C, Frémeaux-Bacchi V et al. The interactive Factor H-atypical hemolytic uremic syndrome mutation database and website: update and integration of membrane cofactor protein and Factor I mutations with structural models.  Hum Mutat. 2007;  28(3) 222-234
• 18 Pichette V, Quérin S, Schürch W, Brun G, Lehner-Netsch G, Delâge J M. Familial hemolytic-uremic syndrome and homozygous factor H deficiency.  Am J Kidney Dis. 1994;  24(6) 936-941
• 19 Ohali M, Shalev H, Schlesinger M et al. Hypocomplementemic autosomal recessive hemolytic uremic syndrome with decreased factor H.  Pediatr Nephrol. 1998;  12(8) 619-624
• 20 Landau D, Shalev H, Levy-Finer G, Polonsky A, Segev Y, Katchko L. Familial hemolytic uremic syndrome associated with complement factor H deficiency.  J Pediatr. 2001;  138(3) 412-417
• 21 Nathanson S, Frémeaux-Bacchi V, Deschênes G. Successful plasma therapy in hemolytic uremic syndrome with factor H deficiency.  Pediatr Nephrol. 2001;  16(7) 554-556
• 22 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
• 23 Licht C, Weyersberg A, Heinen S et al. Successful plasma therapy for atypical hemolytic uremic syndrome caused by factor H deficiency owing to a novel mutation in the complement cofactor protein domain 15.  Am J Kidney Dis. 2005;  45(2) 415-421
• 24 Cho H Y, Lee B S, Moon K C, Ha I S, Cheong H I, Choi Y. Complete factor H deficiency-associated atypical hemolytic uremic syndrome in a neonate.  Pediatr Nephrol. 2007;  22(6) 874-880
• 25 Sethi S K, Marie-Agnes D D, Thaker N, Hari P, Bagga A. Hemolytic uremic syndrome due to homozygous factor H deficiency.  Clin Exp Nephrol. 2009;  13(5) 526-530
• 26 Larakeb A, Leroy S, Frémeaux-Bacchi V et al. Ocular involvement in hemolytic uremic syndrome due to factor H deficiency—are there therapeutic consequences?.  Pediatr Nephrol. 2007;  22(11) 1967-1970
• 27 Stratton J D, Warwicker P. Successful treatment of factor H-related haemolytic uraemic syndrome.  Nephrol Dial Transplant. 2002;  17(4) 684-685
• 28 Gerber A, Kirchhoff-Moradpour A H, Obieglo S et al. Successful (?) therapy of hemolytic-uremic syndrome with factor H abnormality.  Pediatr Nephrol. 2003;  18(9) 952-955
• 29 Davin J C, Strain L, Goodship T HJ. Plasma therapy in atypical haemolytic uremic syndrome: lessons from a family with a factor H mutation.  Pediatr Nephrol. 2008;  23(9) 1517-1521
• 30 Lapeyraque A L, Wagner E, Phan V et al. Efficacy of plasma therapy in atypical hemolytic uremic syndrome with complement factor H mutations.  Pediatr Nephrol. 2008;  23(8) 1363-1366
• 31 Abarrategui-Garrido C, Melgosa M, Peña-Carrión A et al. Mutations in proteins of the alternative pathway of complement and the pathogenesis of atypical hemolytic uremic syndrome.  Am J Kidney Dis. 2008;  52(1) 171-180
• 32 De S, Waters A M, Segal A O, Trautmann A, Harvey E A, Licht C. Severe atypical HUS caused by CFH S1191L—case presentation and review of treatment options.  Pediatr Nephrol. 2010;  25(1) 97-104
• 33 Ferreira V P, Herbert A P, Cortés C et al. The binding of factor H to a complex of physiological polyanions and C3b on cells is impaired in atypical hemolytic uremic syndrome.  J Immunol. 2009;  182(11) 7009-7018
• 34 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
• 35 Richards A, Kemp E J, Liszewski M K et al. Mutations in human complement regulator, membrane cofactor protein (CD46), predispose to development of familial hemolytic uremic syndrome.  Proc Natl Acad Sci U S A. 2003;  100(22) 12966-12971
• 36 Noris M, Brioschi S, Caprioli J International Registry of Recurrent and Familial HUS/TTP et al. Familial haemolytic uraemic syndrome and an MCP mutation.  Lancet. 2003;  362(9395) 1542-1547
• 37 Freméaux-Bacchi V, Moulton E A, Kavanagh D et al. Genetic and functional analyses of membrane cofactor protein (CD46) mutations in atypical hemolytic uremic syndrome.  J Am Soc Nephrol. 2006;  17(7) 2017-2025
• 38 Fang C J, Frémeaux-Bacchi V, Liszewski M K et al. Membrane cofactor protein mutations in atypical hemolytic uremic syndrome (aHUS), fatal Stx-HUS, C3 glomerulonephritis, and the HELLP syndrome.  Blood. 2008;  111(2) 624-632
• 39 Couzi L, Contin-Bordes C, Marliot F et al. Inherited deficiency of membrane cofactor protein expression and varying manifestations of recurrent atypical hemolytic uremic syndrome in a sibling pair.  Am J Kidney Dis. 2008;  52(2) e5-e9
• 40 Davin J C, Buter N, Groothoff J et al. Prophylactic plasma exchange in CD46-associated atypical haemolytic uremic syndrome.  Pediatr Nephrol. 2009;  24(9) 1757-1760
• 41 Saito H, Maruyama I, Shimazaki S et al. Efficacy and safety of recombinant human soluble thrombomodulin (ART-123) in disseminated intravascular coagulation: results of a phase III, randomized, double-blind clinical trial.  J Thromb Haemost. 2007;  5(1) 31-41
• 42 Frémeaux-Bacchi V, Dragon-Durey M A, Blouin J et al. Complement factor I: a susceptibility gene for atypical haemolytic uraemic syndrome.  J Med Genet. 2004;  41(6) e84
• 43 Bienaimé F, Dragon-Durey M A, Regnier C H et al. Mutations in components of complement influence the outcome of factor I-associated atypical hemolytic uremic syndrome.  Kidney Int. 2010;  77(4) 339-349
• 44 Kavanagh D, Kemp E J, Mayland E et al. Mutations in complement factor I predispose to development of atypical hemolytic uremic syndrome.  J Am Soc Nephrol. 2005;  16(7) 2150-2155
• 45 Nilsson S C, Karpman D, Vaziri-Sani F et al. A mutation in factor I that is associated with atypical hemolytic uremic syndrome does not affect the function of factor I in complement regulation.  Mol Immunol. 2007;  44(8) 1835-1844
• 46 Frémeaux-Bacchi V, Miller E C, Liszewski M K et al. Mutations in complement C3 predispose to development of atypical hemolytic uremic syndrome.  Blood. 2008;  112(13) 4948-4952
• 47 Goicoechea de Jorge E, Harris C L, Esparza-Gordillo J et al. Gain-of-function mutations in complement factor B are associated with atypical hemolytic uremic syndrome.  Proc Natl Acad Sci U S A. 2007;  104(1) 240-245
• 48 Roumenina L T, Jablonski M, Hue C et al. Hyperfunctional C3 convertase leads to complement deposition on endothelial cells and contributes to atypical hemolytic uremic syndrome.  Blood. 2009;  114(13) 2837-2845
• 49 Lhotta K, Janecke A R, Scheiring J et al. A large family with a gain-of-function mutation of complement C3 predisposing to atypical hemolytic uremic syndrome, microhematuria, hypertension and chronic renal failure.  Clin J Am Soc Nephrol. 2009;  4(8) 1356-1362
• 50 Ariceta G, Besbas N, Johnson S European Paediatric Study Group for HUS et al. Guideline for the investigation and initial therapy of diarrhea-negative hemolytic uremic syndrome.  Pediatr Nephrol. 2009;  24(4) 687-696
• 51 Ruggenenti P, Noris M, Remuzzi G. Thrombotic microangiopathy, hemolytic uremic syndrome, and thrombotic thrombocytopenic purpura.  Kidney Int. 2001;  60(3) 831-846
• 52 Allford S L, Hunt B J, Rose P, Machin S J. Haemostasis and Thrombosis Task Force, British Committee for Standards in Haematology . Guidelines on the diagnosis and management of the thrombotic microangiopathic haemolytic anaemias.  Br J Haematol. 2003;  120(4) 556-573
• 53 Taylor C M, Machin S, Wigmore S J, Goodship T H. working party from the Renal Association, the British Committee for Standards in Haematology and the British Transplantation Society . Clinical practice guidelines for the management of atypical haemolytic uraemic syndrome in the United Kingdom.  Br J Haematol. 2010;  148(1) 37-47
• 54 Michon B, Moghrabi A, Winikoff R et al. Complications of apheresis in children.  Transfusion. 2007;  47(10) 1837-1842
• 55 Witt V, Stegmayr B, Ptak J et al. World apheresis registry data from 2003 to 2007, the pediatric and adolescent side of the registry.  Transfus Apheresis Sci. 2008;  39(3) 255-260
• 56 Chatelet V, Frémeaux-Bacchi V, Lobbedez T, Ficheux M, Hurault de Ligny B. Safety and long-term efficacy of eculizumab in a renal transplant patient with recurrent atypical hemolytic-uremic syndrome.  Am J Transplant. 2009;  9(11) 2644-2645
• 57 Davin J C, Gracchi V, Bouts A, Groothoff J, Strain L, Goodship T. Maintenance of kidney function following treatment with eculizumab and discontinuation of plasma exchange after a third kidney transplant for atypical hemolytic uremic syndrome associated with a CFH mutation.  Am J Kidney Dis. 2010;  55(4) 708-711
• 58 Nürnberger J, Philipp T, Witzke O et al. Eculizumab for atypical hemolytic-uremic syndrome.  N Engl J Med. 2009;  360(5) 542-544
• 59 Gruppo R A, Rother R P. Eculizumab for congenital atypical hemolytic-uremic syndrome.  N Engl J Med. 2009;  360(5) 544-546