Recurrence of hemolytic uremic syndrome after live related renal transplantation associated with subsequent de novo disease in the donor

Donne, Rosie; Abbs, I C; Bárány, Peter; Elinder, Carl‐Gustaf; Little, Mark A.; Conlon, Peter J.; Goodship, Timothy H.J.

doi:10.1053/ajkd.2002.36938

Cited by 70 publications

(48 citation statements)

References 11 publications

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“…This is not unexpected as IF, like CFH, is predominantly synthesized by the liver and thus a renal allograft will not correct the underlying defect. From individuals reported in the literature and unpublished from our own cohort, the recurrence rate in those with CFH mutations and/or CFH deficiency is approximately 80% (2,4,6,7,(25)(26)(27)(28)(29)(30).…”

Section: Discussionmentioning

confidence: 97%

“…It is important in patients who are being considered for transplantation that it be known whether they have a CFH, IF, or MCP mutation so that they can be informed appropriately of the risks for recurrence. We would not recommend live related transplantation in patients who are known to have either a CFH or an IF mutation unless the donor has been screened for the same mutation, as de novo HUS has been reported to occur in donors within a short period of time after surgery (26). Even if the living related donor is known not to carry the same mutation, the risk for recurrence in the recipient is likely to be as high as observed with cadaveric donors, a risk that some would consider to be unacceptably high for any transplant.…”

Section: Discussionmentioning

confidence: 99%

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Mutations in Complement Factor I Predispose to Development of Atypical Hemolytic Uremic Syndrome

Kavanagh¹,

Kemp²,

Mayland³

et al. 2005

Journal of the American Society of Nephrology

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315

168

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Mutations in the plasma complement regulator factor H (CFH) and the transmembrane complement regulator membrane co-factor protein (MCP) have been shown to predispose to atypical hemolytic uremic syndrome (HUS). Both of these proteins act as co-factors for complement factor I (IF). IF is a highly specific serine protease that cleaves the ␣-chains of C3b and C4b and thus downregulates activation of both the classical and the alternative complement pathways. This study looked for IF mutations in a panel of 76 patients with HUS. Mutations were detected in two patients, both of whom had reduced serum IF levels. A heterozygous bp change, c.463 G>A, which results in a premature stop codon (W127X), was found in one, and in the other, a heterozygous single base pair deletion in exon 7 (del 922C) was detected. Both patients had a history of recurrent HUS after transplantation. This is in accordance with the high rate of recurrence in patients with CFH mutations. Patients who are reported to have mutations in MCP, by contrast, do not have recurrence after transplantation. As with CFH-and MCPassociated HUS, there was incomplete penetrance in the family of one of the affected individuals. This study provides further evidence that atypical HUS is a disease of complement dysregulation.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Mutations in Complement Factor I Predispose to Development of Atypical Hemolytic Uremic Syndrome

Kavanagh¹,

Kemp²,

Mayland³

et al. 2005

Journal of the American Society of Nephrology

Self Cite

315

168

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“…Patients who lost the first kidney graft for recurrence should not receive another transplant. Liverelated renal transplant should also be avoided in that it carries the additional risk to precipitate the disease onset in the healthy donor relative as recently reported in two families (156). New knowledge from genetic studies will predict more accurately the risk for recurrence.…”

Section: Which Treatment For Non-stx-hus?mentioning

confidence: 98%

Hemolytic Uremic Syndrome

Noris¹,

Remuzzi²

2005

Journal of the American Society of Nephrology

502

428

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“…The results of such screening are often biased by: the inadequacy of the screening and the incomplete penetrance of several mutations. In addition to the risk of relapse in the recipient, the development of aHUS in asymptomatic donors has been reported [124] . Several studies have suggested that calcineurin inhibitors, which have endothelial toxicity, should be avoided; however, mTOR inhibitors may also be toxic to the endothelium, through the down-regulation of vascular endothelial growth factor (VEGF) [125,126] .…”

Section: Renal Transplantationmentioning

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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Recurrence of hemolytic uremic syndrome after live related renal transplantation associated with subsequent de novo disease in the donor

Cited by 70 publications

References 11 publications

Mutations in Complement Factor I Predispose to Development of Atypical Hemolytic Uremic Syndrome

Mutations in Complement Factor I Predispose to Development of Atypical Hemolytic Uremic Syndrome

Hemolytic Uremic Syndrome

Update on hemolytic uremic syndrome: Diagnostic and therapeutic recommendations

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