Busutti, Marco
(2022)
Efficacia del Tocilizumab nel trattamaneto del rigetto umorale cronico attivo nel paziente trapiantato di rene, [Dissertation thesis], Alma Mater Studiorum Università di Bologna.
Dottorato di ricerca in
Scienze cardio nefro toraciche, 34 Ciclo. DOI 10.48676/unibo/amsdottorato/10216.
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Abstract
In the last decades significant improvements has been reached in short term graft survival, conversely long-term graft survival in still an open challenge for the scientific community. One of the major causes of long term graft loss is represented by chronic- active antibody mediated rejection (cAMR), a recently identified entity whose diagnosis is based on laboratoristic and histologic elements: the presence of DSA associated to specific morphological lesions as inflammation and microvascular damage associated or not to C4d deposition. Treatment of cAMR is an open field of debate. Tocilizumab, an anti-IL6 monoclonal antibody has been recently proposed as a first line treatment for cAMR, showing encouranging results.
We describe our monocentric experience using Tocilizumab as first-line therapy for cAMR.
Graft function (eGFR), proteinuria and DSA have been evaluated every 6 month for 24 months; histology have been performed after 12 months of treatment.
No adverse events have been observed during study period.
12 patients completed the study with a follow-up of 24 months. Kidney function showed a worsening during follow-up that reaches statistical significance at 12 and 24 months (eGFR from 32.2±13.9 ml/min to 26.9±13 ml/min), but far less than expected for these kind of patients. 4 patients (30%) reached ESRD during follow-up, 3 requiring renal replacement therapy.
We did not observed any statically significant variation in proteinuria and in DSA MFI levels.
From a histological point of view, we observed a significant improvement in active cAMR lesions (C4d deposition and Acute tissue injury (MTA, g>0/ptc>0, v>0) and no progression among chronic lesions (Transplant glomerulopathy, PTC multilayering and aterial intimal fibrosis)
Tocilizumab shown good results, with a stabilization of graft function, a reduction in kidney inflammation and active lesions in kidney biopsy and not allowing progression of chronic lesions.
Abstract
In the last decades significant improvements has been reached in short term graft survival, conversely long-term graft survival in still an open challenge for the scientific community. One of the major causes of long term graft loss is represented by chronic- active antibody mediated rejection (cAMR), a recently identified entity whose diagnosis is based on laboratoristic and histologic elements: the presence of DSA associated to specific morphological lesions as inflammation and microvascular damage associated or not to C4d deposition. Treatment of cAMR is an open field of debate. Tocilizumab, an anti-IL6 monoclonal antibody has been recently proposed as a first line treatment for cAMR, showing encouranging results.
We describe our monocentric experience using Tocilizumab as first-line therapy for cAMR.
Graft function (eGFR), proteinuria and DSA have been evaluated every 6 month for 24 months; histology have been performed after 12 months of treatment.
No adverse events have been observed during study period.
12 patients completed the study with a follow-up of 24 months. Kidney function showed a worsening during follow-up that reaches statistical significance at 12 and 24 months (eGFR from 32.2±13.9 ml/min to 26.9±13 ml/min), but far less than expected for these kind of patients. 4 patients (30%) reached ESRD during follow-up, 3 requiring renal replacement therapy.
We did not observed any statically significant variation in proteinuria and in DSA MFI levels.
From a histological point of view, we observed a significant improvement in active cAMR lesions (C4d deposition and Acute tissue injury (MTA, g>0/ptc>0, v>0) and no progression among chronic lesions (Transplant glomerulopathy, PTC multilayering and aterial intimal fibrosis)
Tocilizumab shown good results, with a stabilization of graft function, a reduction in kidney inflammation and active lesions in kidney biopsy and not allowing progression of chronic lesions.
Tipologia del documento
Tesi di dottorato
Autore
Busutti, Marco
Supervisore
Dottorato di ricerca
Ciclo
34
Coordinatore
Settore disciplinare
Settore concorsuale
Parole chiave
kidney, transplantation, rejetion, tocilizumab
URN:NBN
DOI
10.48676/unibo/amsdottorato/10216
Data di discussione
8 Luglio 2022
URI
Altri metadati
Tipologia del documento
Tesi di dottorato
Autore
Busutti, Marco
Supervisore
Dottorato di ricerca
Ciclo
34
Coordinatore
Settore disciplinare
Settore concorsuale
Parole chiave
kidney, transplantation, rejetion, tocilizumab
URN:NBN
DOI
10.48676/unibo/amsdottorato/10216
Data di discussione
8 Luglio 2022
URI
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