A phase I/II placebo-controlled trial of C1-inhibitor for prevention of antibody-mediated rejection in HLA sensitized patients.
Transplantation
; 99(2): 299-308, 2015 Feb.
Article
en En
| MEDLINE
| ID: mdl-25606785
ABSTRACT
BACKGROUND:
Antibody-mediated rejection (AMR) is a severe form of rejection, mediated primarily by antibody-dependent complement (C) activation. C1 inhibitor (C1-INH, Berinert) inhibits the classical and lectin pathways of C activation. We performed a randomized, placebo-controlled study using C1-INH in highly sensitized renal transplant recipients for prevention of AMR.METHODS:
Twenty highly sensitized patients desensitized with IVIG+rituximab±plasma exchange were enrolled and randomized 11 to receive plasma-derived human C1-INH (20 IU/kg/dose) versus placebo intraoperatively, then twice weekly for 7 doses. Renal function, adverse events (AEs)/serious AEs, C3, C4, and C1-INH levels were monitored and C1q+ HLA antibodies were also blindly assessed.RESULTS:
One patient in the C1-INH group versus 2 patients in the placebo group developed serious AEs, but none were related to study drug. Delayed graft function developed in 1 C1-INH subject and 4 in the placebo. The C1-INH trough levels increased with C1-INH treatment. C3 and C4 levels also increased significantly in the C1-INH group compared to placebo. No C1-INH patient developed AMR during the study. Two patients developed AMR after the study. Three placebo patients developed AMR, one during the study. C1q+ donor specific antibodies were reduced in 2 C1-INH treated patients tested, while immunoglobulin G DSA levels showed decreased binding for both groups.CONCLUSIONS:
The C1-INH appears safe in the posttransplant period. The C1-INH treatment may reduce ischemia-reperfusion injury. The C1-INH also resulted in significant elevations of C1-INH levels, C3, C4, and reduced C1q+ HLA antibodies. Taken together, the combination of antibody reduction and C1-INH may prove useful in prevention of AMR. Further controlled studies are warranted.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Trasplante de Riñón
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Activación de Complemento
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Proteína Inhibidora del Complemento C1
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Rechazo de Injerto
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Supervivencia de Injerto
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Histocompatibilidad
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Antígenos HLA
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Inmunosupresores
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Isoanticuerpos
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Fallo Renal Crónico
Tipo de estudio:
Clinical_trials
/
Diagnostic_studies
Límite:
Adult
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Female
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Humans
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Male
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Middle aged
País/Región como asunto:
America do norte
Idioma:
En
Revista:
Transplantation
Año:
2015
Tipo del documento:
Article
País de afiliación:
Canadá