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Zimmerhackl LB Scheiring J Prüfer F Taylor CM Loirat C 《Pediatric nephrology (Berlin, Germany)》2007,22(1):10-16
Haemolytic uraemic syndrome (HUS) is the primary diagnosis of 4.5% of children on chronic renal replacement therapy. Approximately
5% of all HUS cases have an “atypical” or recurrent course. Atypical HUS is an inadequate term that applies to a heterogeneous
group of conditions. We describe this group as non-diarrhoeal (D
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), non-EHEC (EHEC
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) HUS. Patients in the non-diarrhoeal, non-EHEC, relapsing group are much more likely to exhibit severe hypertension, histological
findings of arterial as well as arteriolar disease, chronic and end-stage renal failure. In general, these patients have an
alarmingly high risk of graft loss from disease recurrence or thrombosis ranging from 60–100%. Family history is crucial,
and where family members have relapsing disease, transplantation is a very high risk procedure (recurrence 100%). Patients
with D–HUS need very careful consideration before transplantation, including molecular investigation of complement regulators (and
von Willebrandt protease (ADAMTS13) activity, although this goes beyond the scope of this review). Guidelines are accessible
under . On no account should live related donation take place unless the risks of graft loss are understood. International collaboration
to identify safer ways of transplanting these challenging patients is urgently needed. 相似文献
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Julien Zuber Moglie Le Quintrec Heather Morris Véronique Frémeaux-Bacchi Chantal Loirat Christophe Legendre 《Transplantation reviews (Orlando, Fla.)》2013,27(4):117-125
Atypical hemolytic and uremic syndrome (aHUS) is associated with a high rate of recurrence and poor outcomes after kidney transplantation. Fortunately, recent advances in the understanding of the pathogenesis of aHUS have permitted an individualized risk assessment of post-transplant recurrence. Acquired or inherited dysregulation of the alternative complement pathway, thought to be the driving force of the disease, is identified in most aHUS patients. Notably, depending on the mutations involved, the risk of recurrence greatly varies, highlighting the importance of undertaking etiological investigations prior to kidney transplantation. In those with moderate to high risk of recurrence, the use of a prophylactic therapy, consisting in either plasmapheresis or eculizumab therapies, represents a major stride forward in the prevention of aHUS recurrence after kidney transplantation. In those who experience aHUS recurrence, a growing number of observations suggest that eculizumab therapy outperforms curative plasma therapy. The optimal duration of both prophylactic and curative therapies remains an important, yet unaddressed, issue. In this respect, the kidney transplant recipients, continuously exposed to endothelial-insulting factors, referred here as to triggers, might have a sustained high risk of recurrence. A global therapeutic approach should thus attempt to reduce exposure to these triggers. 相似文献
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Gwenaëlle Sana Marie-Agnès Dragon-Durey Marina Charbit Karim Bouchireb Caroline Rousset-Rouvière Etienne Bérard Rémi Salomon Véronique Frémeaux-Bacchi Patrick Niaudet Olivia Boyer 《Pediatric nephrology (Berlin, Germany)》2014,29(1):75-83
Background
Anti-complement factor H (CFH) autoantibody (Ab)-associated atypical hemolytic uremic syndrome (aHUS) has a poor prognosis, but no consensus exists on its treatment.Methods
We report the follow-up of four children with anti-CFH Ab (8,000 to >32,000 arbitrary units)-associated aHUS after plasma exchanges (PEs), prednisone, and cyclophosphamide pulse therapy with the evolution of anti-CFH Ab titers and kidney function.Results
Patient 1 received PEs + prednisone + cyclophosphamide pulses after two relapses following PEs and then PEs + rituximab. The other three patients were treated with PEs + prednisone + cyclophosphamide pulses as a first-line therapy. In our four patients, the induction protocol combining PEs + prednisone + cyclophosphamide pulses led to a rapid and sustained remission up to 6 years, 4 years and 4 months without any maintenance therapy. Kidney function was normal and anti-CFH Ab titer decreased, but remained detectable during remission without any clinical or biological signs of relapse.Conclusions
We demonstrate the long-term efficiency and safety of cyclophosphamide pulses combined with PEs and prednisone in anti-CFH Ab-associated aHUS leading to a prolonged decrease in anti-CFH Ab titers and prevention of relapses without the need for maintenance therapy. 相似文献6.
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BACKGROUND: Hemolytic uremic syndrome (HUS) is a disease characterized by nonimmune hemolytic anemia, thrombocytopenia and renal impairment. There are many causes for HUS, but adverse reactions to drugs have been increasingly reported. Even the NSAIDs which have been reported as safe and effective painkillers are described as cause of recurrent HUS. PATIENT CASE: We describe a case of a 44-year-old woman who was admitted to our hospital because of thrombocytopenia and anemia after the use of 8 tablets of 400 mg ibuprofen (NSAIDs). The diagnosis HUS was made and she recovered completely after treatment with fresh-frozen plasma and seven plasma exchanges. CONCLUSION: No cause could be identified except the use of ibuprofen. Recognition of a drug-induced HUS is necessary to avoid reexposure and recurrent HUS. 相似文献
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Peraldi M; Maslo C; Berrou J; Rondeau E; Rozenbaum W; Sraer J 《Nephrology, dialysis, transplantation》1998,13(4):919-923
Background: In children, haemolytic uraemic syndrome
(HUS) is associated with high plasma plasminogen activator inhibitor type 1
(PAI-1), which may contribute to the persistence of renal glomerular and
arteriolar thrombi. HUS has been described in HIV-infected patients, but
the pathophysiology of HUS in these patients is poorly understood. The aim
of the study was to investigate plasma fibrinolytic activity in 18 patients
with HIV-associated HUS. Methods: We measured tissue
type plasminogen activator (t-PA) and PAI-1 activities in the plasma of 18
HIV-infected patients with biopsy-proven HUS (HIV+/HUS+0 and 48
HIV-infected patients without HUS (HIV+/HUS-).
Results: Patients with HUS had a significantly higher
serum creatinine, a lower platelet count and an increased incidence of
cytomegalovirus (CMV) infection (72% of patients HIV+/HUS+,
vs 25% of patients HIV+/HUS-). Unexpectedly, plasma
PAI-1 activity was similar in both groups. However, t-PA activity was
significantly higher in HUS cases (11.5 vs 4.5 U/ml,
P=0.001). Patients with CMV infection, with or without HUS, had
significantly increased t-PA level (P=0.01). Multivariate analysis
identified high t-PA (RR=9.21) and CMV infection (RR=3.36) as risk factors
for HUS. Conclusion: This study provides evidence that
HIV-infected patients with HUS have high plasma t-PA activity. PAI-1 plasma
activity is not significantly increased, as opposed to non-HIV-associated
HUS. Thus, in the setting of HIV infection, HUS cannot be attributed to
decreased fibrinolytic activity. 相似文献
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Kavanagh D Kemp EJ Mayland E Winney RJ Duffield JS Warwick G Richards A Ward R Goodship JA Goodship TH 《Journal of the American Society of Nephrology : JASN》2005,16(7):2150-2155
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 alpha-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 MCP-associated 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. 相似文献
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Differential impact of complement mutations on clinical characteristics in atypical hemolytic uremic syndrome 总被引:4,自引:0,他引:4
Sellier-Leclerc AL Fremeaux-Bacchi V Dragon-Durey MA Macher MA Niaudet P Guest G Boudailliez B Bouissou F Deschenes G Gie S Tsimaratos M Fischbach M Morin D Nivet H Alberti C Loirat C;French Society of Pediatric Nephrology 《Journal of the American Society of Nephrology : JASN》2007,18(8):2392-2400
Mutations in factor H (CFH), factor I (IF), and membrane cofactor protein (MCP) genes have been described as risk factors for atypical hemolytic uremic syndrome (aHUS). This study analyzed the impact of complement mutations on the outcome of 46 children with aHUS. A total of 52% of patients had mutations in one or two of known susceptibility factors (22, 13, and 15% of patients with CFH, IF, or MCP mutations, respectively; 2% with CFH+IF mutations). Age <3 mo at onset seems to be characteristic of CFH and IF mutation-associated aHUS. The most severe prognosis was in the CFH mutation group, 60% of whom reached ESRD or died within <1 yr. Only 30% of CFH mutations were localized in SCR20. MCP mutation-associated HUS has a relapsing course, but none of the children reached ESRD at 1 yr. Half of patients with IF mutation had a rapid evolution to ESRD, and half recovered. Plasmatherapy seemed to have a beneficial effect in one third of patients from all groups except for the MCP mutation group. Only eight (33%) of 24 kidney transplantations that were performed in 15 patients were successful. Graft failures were due to early graft thrombosis (50%) or HUS recurrence. In conclusion, outcome of HUS in patients with CFH mutation is catastrophic, and posttransplantation outcome is poor in all groups except for the MCP mutation group. New therapies are urgently needed, and further research should elucidate the unexplained HUS group. 相似文献
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de Jorge EG Macor P Paixão-Cavalcante D Rose KL Tedesco F Cook HT Botto M Pickering MC 《Journal of the American Society of Nephrology : JASN》2011,22(1):137-145
Gene variants in the alternative pathway of the complement system strongly associate with atypical hemolytic uremic syndrome (aHUS), presumably by predisposing to increased complement activation within the kidney. Complement factor H (CFH) is the major regulator of complement activation through the alternative pathway. Factor H-deficient mice transgenically expressing a mutant CFH protein (Cfh(-/-).FHΔ16-20) that functionally mimics the CFH mutations reported in aHUS patients spontaneously develop thrombotic microangiopathy. To investigate the role of complement C5 activation in this aHUS model, we generated C5-deficient Cfh(-/-).FHΔ16-20 mice. Both C5-sufficient and C5-deficient Cfh(-/-).FHΔ16-20 mice had abnormal C3 deposition within the kidney, but spontaneous aHUS did not develop in any of the C5-deficient mice. Furthermore, although Cfh(-/-).FHΔ16-20 animals demonstrated marked hypersensitivity to experimentally triggered renal injury, animals with concomitant C5 deficiency did not. These data demonstrate a critical role for C5 activation in both spontaneous aHUS and experimentally triggered renal injury in animals with defective complement factor H function. This study provides a rationale to investigate therapeutic inhibition of C5 in human aHUS. 相似文献
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We report a case of sporadic atypical hemolytic uremic syndrome (HUS) with a transient decrease in complement factor H. Referred for hemolysis and azotemia without diarrhea prodrome, this 31-month-old boy showed a decreased complement 3 (C3) and complement factor H (FH) level. However, the factor H gene (HF1) mutation was missing. After the hemolysis was controlled with plasma infusion, the C3 and FH levels recovered. The patients renal function fully recovered and remained normal, and there was no recurrence of the HUS. 相似文献
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I. R. Marino S. Celli G. Ferla H. R. Doyle N. Maggiano G. Zetti P. Musiani 《Transplant international》1992,5(Z1):S320-S322
In pig-to-rabbit kidney xenograft (PRKX), endothelial antigen determinants (EAD) are immediately recognized by IgG and IgA, while IgM does not react with them. The purpose of this study was to investigate the different roles of IgG, IgA, IgM, and complement in the hyperacute rejection of a PRKX model. Nine isolated Landrace pig kidneys were each perfused with 10 ml normal New Zealand rabbit serum. Perfusates (serum A) were collected after discarding the first 0.5 ml. Serum A and rabbit complement were then incubated for 30 min with frozen sections of normal pig kidney. After washing with buffer solution all the specimens were treated for immunohistochemistry. Three frozen sections of normal Landrace pig kidney and three samples of normal New Zealand rabbit serum were used as controls. Immunohistochemical analysis of the nine perfused kidneys demonstrated IgG, IgA and C3 deposition on the peritubular and glomerular vascular endothelium. No IgM reactivity was shown. In the frozen sections exposed to serum A, immunofluorescence showed minimal IgG, IgA and C3 reactivity while IgM deposition was clearly evident on the tubular epithelium. Immunofluorescence of frozen sections exposed to rabbit complement, done by fluorescein-labeled goat anti-rabbit C3 antibodies were positive only in the glomerular endothelium. The same rabbit complement was active in antibody dependent cytotoxicity on human T cells. Our results indicated that in the PRKX model, IgG and IgA acted as preformed antibodies recognizing endothelial EAD. IgM did not bind to any endothelial molecules, but recognized antigens located on the brush border of the tubular epithelium. Furthermore, in this model, absence of antigen-antibody complexes resulted in atypical complement deposition. 相似文献