Eculizumab for Atypical Hemolytic Uremic Syndrome Recurrence in Renal Transplantation

Zuber, Julien; Quintrec, Moglie Le; Krid, Saoussen; Prot-Bertoye, Caroline; Gueutin, Victor; Lahoche, Annie; Heyne, Nils; Ardissino, Gianluigi; Châtelet, Valérie; Nôël, Laure-Hélène; Hourmant, Maryvonne; Niaudet, Patrick; Frémeaux‐Bacchi, Véronique; Rondeau, Éric; Legendre, Christophe; Loirat, Chantal

doi:10.1111/j.1600-6143.2012.04252.x

Cited by 238 publications

(225 citation statements)

References 41 publications

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“…Between 2000 and 2008, the mean number of patients referred each year at the time of the first episode of aHUS was 15 (range, [8][9][10][11][12][13][14][15][16][17][18][19][20][21], suggesting that the annual incidence of aHUS is at least 0.23/year per 10 6 people in the French population.…”

Section: Resultsmentioning

confidence: 99%

Genetics and Outcome of Atypical Hemolytic Uremic Syndrome

Frémeaux‐Bacchi¹,

Fakhouri²,

Garnier³

et al. 2013

Clinical Journal of the American Society of Nephrology

637

765

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SummaryBackground and objectives Atypical hemolytic uremic syndrome (aHUS) is a rare complement-mediated kidney disease that was first recognized in children but also affects adults. This study assessed the disease presentation and outcome in a nationwide cohort of patients with aHUS according to the age at onset and the underlying complement abnormalities.Design, setting, participants, & measurements A total of 214 patients with aHUS were enrolled between 2000 and 2008 and screened for mutations in the six susceptibility factors for aHUS and for anti-factor H antibodies.Results Onset of aHUS occurred as frequently during adulthood (58.4%) as during childhood (41.6%). The percentages of patients who developed the disease were 23%, 40%, 70%, and 98% by age 2, 18, 40, and 60 years, respectively. Mortality was higher in children than in adults (6.7% versus 0.8% at 1 year) (P=0.02), but progression to ESRD after the first aHUS episode was more frequent in adults (46% versus 16%; P,0.001). Sixty-one percent of patients had mutations in their complement genes. The renal outcome was not significantly different in adults regardless of genetic background. Only membrane cofactor protein (MCP) and undetermined aHUS were less severe in children than adults. The frequency of relapse after 1 year was 92% in children with MCP-associated HUS and approximately 30% in all other subgroups.Conclusion Mortality rate was higher in children than adults with aHUS, but renal prognosis was worse in adults than children. In children, the prognosis strongly depends on the genetic background.

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Section: Resultsmentioning

confidence: 99%

Genetics and Outcome of Atypical Hemolytic Uremic Syndrome

Frémeaux‐Bacchi¹,

Fakhouri²,

Garnier³

et al. 2013

Clinical Journal of the American Society of Nephrology

637

765

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“…More recently, eculizumab efficacy was also documented in aHUS recurrence after renal transplantation [134] . Overall, these data suggest that long-term eculizumab treatment is highly effective for the prevention and treatment of post-transplant aHUS recurrence and indicate that anti-C5 therapy should be started promptly after a recurrence.…”

Section: Eculizumabmentioning

confidence: 99%

Update on hemolytic uremic syndrome: Diagnostic and therapeutic recommendations

Salvadori

Bertoni²

2013

WJN

116

111

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Hemolytic uremic syndrome (HUS) is a rare disease. In this work the authors review the recent findings on HUS, considering the different etiologic and pathogenetic classifications. New findings in genetics and, in particular, mutations of genes that encode the complement-regulatory proteins have improved our understanding of atypical HUS. Similarly, the complement proteins are clearly involved in all types of thrombotic microangiopathy: typical HUS, atypical HUS and thrombotic thrombocytopenic purpura (TTP). Furthermore, several secondary HUS appear to be related to abnormalities in complement genes in predisposed patients. The authors highlight the therapeutic aspects of this rare disease, examining both "traditional therapy" (including plasma therapy, kidney and kidneyliver transplantation) and "new therapies". The latter include anti-Shiga-toxin antibodies and anti-C5 monoclonal antibody "eculizumab". Eculizumab has been recently launched for the treatment of the atypical HUS, but it appears to be effective in the treatment of typical HUS and in TTP. Future therapies are in phases Ⅰ and Ⅱ. They include anti-C5 antibodies, which are more purified, less immunogenic and absorbed orally and, anti-C3 antibodies, which are more powerful, but potentially less safe. Additionally, infusions of recombinant complement-regulatory proteins are a potential future therapy.

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“…This antibody prevents the formation of C5b and the C5b-C9 complex (membrane attack complex), and the recent findings indicate that anti-C5 is effective in treating aHUS patients. Moreover, recent data suggest that eculizumab is effective in preventing and treating post-transplant recurrences of aHUS after isolated KT [36]. The first two doses can be given just before and after KT followed by maintenance infusions at 2-week intervals.…”

Section: Clkt In Different Indicationsmentioning

confidence: 99%

Combined liver and kidney transplantation in children

Jalanko

Pakarinen

2013

Pediatr Nephrol

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Simultaneous combined liver-kidney transplantation (CLKT) is a rare operation in pediatric patients so that annually only 10-30 operations are performed worldwide. The main indications for CLKT are primary hyperoxaluria type 1 and autosomal recessive polycystic kidney disease. In addition, CLKT is indicated in individual patients with metabolic or cirrhotic liver diseases and end-stage kidney disease. The surgery and immediate post-operative management of CLKT remain challenging in infants and small children. The patients should be operated on before they become severely ill or develop major systemic manifestations of their metabolic disorder. The liver allograft is immunologically protective of the kidney graft in simultaneous CLKT, often resulting in well-preserved kidney function. The long-term outcome after CLKT is nowadays comparable to that of isolated liver and kidney transplantations.

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Eculizumab for Atypical Hemolytic Uremic Syndrome Recurrence in Renal Transplantation

Cited by 238 publications

References 41 publications

Genetics and Outcome of Atypical Hemolytic Uremic Syndrome

Genetics and Outcome of Atypical Hemolytic Uremic Syndrome

Update on hemolytic uremic syndrome: Diagnostic and therapeutic recommendations

Combined liver and kidney transplantation in children

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