Successful Split Liver-Kidney Transplant for Factor H Associated Hemolytic Uremic Syndrome

Saland, Jeffrey M.; Shneider, Benjamin L.; Bromberg, Jonathan S.; Shi, Patricia A.; Ward, Stephen; Magid, Margret S.; Benchimol, Corinne; Seikaly, Mouin G.; Emre, Sükrü; Bresin, Elena

doi:10.2215/cjn.02170508

Cited by 62 publications

(43 citation statements)

References 38 publications

(34 reference statements)

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“…Because CFH, CFI, and C3 are plasma proteins synthesized predominantly by the liver, kidney transplantation alone does not correct the defect. As reported previously, simultaneous liver-kidney transplantation prevented recurrences in patients with CFH mutations but had a high mortality rate (23,24,39,40).…”

Section: Discussionsupporting

confidence: 60%

Relative Role of Genetic Complement Abnormalities in Sporadic and Familial aHUS and Their Impact on Clinical Phenotype

Noris¹,

Caprioli²,

Bresin³

et al. 2010

Clinical Journal of the American Society of Nephrology

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910

1,194

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Background and objectives: Hemolytic uremic syndrome (HUS) is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment. Most childhood cases are caused by Shiga toxin-producing bacteria. The other form, atypical HUS (aHUS), accounts for 10% of cases and has a poor prognosis. Genetic complement abnormalities have been found in aHUS.Design, setting, participants, and measurements: We screened 273 consecutive patients with aHUS for complement abnormalities and studied their role in predicting clinical phenotype and response to treatment. We compared mutation frequencies and localization and clinical outcome in familial (82) and sporadic (191) cases.Results: In >70% of sporadic and familial cases, gene mutations, disease-associated factor H (CFH) polymorphisms, or anti-CFH autoantibodies were found. Either mutations or CFH polymorphisms were also found in the majority of patients with secondary aHUS, suggesting a genetic predisposition. Familial cases showed a higher prevalence of mutations in SCR20 of CFH and more severe disease than sporadic cases. Patients with CFH or THBD (thrombomodulin) mutations had the earliest onset and highest mortality. Membrane-cofactor protein (MCP) mutations were associated with the best prognosis. Plasma therapy induced remission in 55 to 80% of episodes in patients with CFH, C3, or THBD mutations or autoantibodies, whereas patients with CFI (factor I) mutations were poor responders. aHUS recurred frequently after kidney transplantation except for patients with MCP mutations.Conclusions: Results underline the need of genetic screening for all susceptibility factors as part of clinical management of aHUS and for identification of patients who could safely benefit from kidney transplant.

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Section: Discussionsupporting

confidence: 60%

Relative Role of Genetic Complement Abnormalities in Sporadic and Familial aHUS and Their Impact on Clinical Phenotype

Noris¹,

Caprioli²,

Bresin³

et al. 2010

Clinical Journal of the American Society of Nephrology

Self Cite

910

1,194

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“…On the basis of the pathophysiology of aHUS, several combined liver-kidney transplants have been done with the goal to have the transplanted liver supply normal complement regulatory proteins in those aHUS patients with mutations in liver-derived factors (CFH, CFI, CFB, and C3) (25)(26)(27)(28)(29)(30). However, this approach does not address the problem in aHUS patients with CFH autoantibodies and carries a significant added risk when considering the possibility of increased complement activation and the increased complexity of a dual organ transplant.…”

Section: Discussionmentioning

confidence: 99%

Pre-emptive Eculizumab and Plasmapheresis for Renal Transplant in Atypical Hemolytic Uremic Syndrome

Nester

Stewart²,

Myers

et al. 2011

Clinical Journal of the American Society of Nephrology

117

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SummaryThe case of a 12-year-old with a hybrid CFH/CFHL1 gene and atypical hemolytic uremic syndrome (aHUS) that had previously developed native kidney and then renal allograft loss is reported. This case illustrates the relatively common occurrence of renal loss from the late presentation of aHUS. Also presented is a protocol for the pre-emptive use of eculizumab and plasmapheresis as part of a renal transplant plan for the treatment of aHUS in patients deemed at high risk for recurrent disease. This protocol was a result of a multidisciplinary approach including adult and pediatric nephrology, transplant surgery, transfusion medicine, and infectious disease specialists. This protocol and the justifications and components of it can function as a guideline for the treatment of a group of children that have waited in limbo for the first U.S. transplant to open the door to this type of definitive care for this devastating disease.

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“…29 Because both factor H and factor I are produced mainly by the liver, combined liver/kidney transplantation is a logical therapeutic option. Whereas the outcome in initial reports of this modality was less favorable, 30 more recent reports [31][32][33] suggest that a favorable long-term outcome is possible. Pivotal to this is the use of prophylactic plasma exchange immediately before surgery.…”

Section: Investigation and Treatment Of Ahusmentioning

confidence: 95%

Atypical Hemolytic Uremic Syndrome, Genetic Basis, and Clinical Manifestations

Kavanagh

Goodship

2011

Hematology

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Atypical hemolytic uremic syndrome (aHUS) is now well recognized to be a disease characterized by excessive complement activation in the microvasculature. In both the familial and sporadic forms, inherited and acquired abnormalities affecting components of the alternative complement pathway are found in ϳ 60% of patients. These include mutations in the genes encoding both complement regulators (factor H, factor I, membrane cofactor protein, and thrombomodulin) and activators (factors B and C3) and autoantibodies against factor H. Multiple hits are necessary for the disease to manifest, including a trigger, mutations, and at-risk haplotypes in complement genes. The prognosis for aHUS is poor, with most patients developing end-stage renal failure. Renal transplantation in most patients also has a poor prognosis, with frequent loss of the allograft to recurrent disease. However, improving results with combined liver-kidney transplantation and the advent of complement inhibitors such as eculizumab offer hope that the prognosis for aHUS will improve in future years.

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Successful Split Liver-Kidney Transplant for Factor H Associated Hemolytic Uremic Syndrome

Cited by 62 publications

References 38 publications

Relative Role of Genetic Complement Abnormalities in Sporadic and Familial aHUS and Their Impact on Clinical Phenotype

Relative Role of Genetic Complement Abnormalities in Sporadic and Familial aHUS and Their Impact on Clinical Phenotype

Pre-emptive Eculizumab and Plasmapheresis for Renal Transplant in Atypical Hemolytic Uremic Syndrome

Atypical Hemolytic Uremic Syndrome, Genetic Basis, and Clinical Manifestations

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