Gianluigi Ardissino1, Donata Cresseri2, Francesca Tel3, Antenore Giussani4, Stefania Salardi5, Martina Sgarbanti5, Bice Strumbo5, Sara Testa3, Valentina Capone3, Samantha Griffini6, Elena Grovetti6, Massimo Cugno6, Mirco Belingheri2, Chiara Tamburello3, Evangeline Millicent Rodrigues3, Michela Perrone7, Massimo Cardillo8, Grazia Corti9, Dario Consonni10, Lucrezia Furian11, Silvana Tedeschi5, Piergiorgio Messa2, Claudio Beretta4. 1. Pediatric Nephrology, Dialysis and Transplantation Unit, Center for HUS Control, Prevention and Management, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, V. Commenda, 9, 20122, Milan, Italy. ardissino@centroseu.org. 2. Nephrology Unit, Center for HUS Prevention, Control and Management, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. 3. Pediatric Nephrology, Dialysis and Transplantation Unit, Center for HUS Control, Prevention and Management, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, V. Commenda, 9, 20122, Milan, Italy. 4. Kidney Transplant Unit, Center for HUS Prevention, Control and Management, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. 5. Molecular Biology Laboratory, Center for HUS Prevention, Control and Management, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. 6. Internal Medicine, Center for HUS Prevention, Control and Management, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. 7. Neonatal Intensive Care Unit, Center for HUS Prevention, Control and Management, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. 8. North Italian Transplant, Center for HUS Prevention, Control and Management, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. 9. Pharmacy, Center for HUS Prevention, Control and Management, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. 10. Epidemiology Unit, Center for HUS Prevention, Control and Management, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. 11. Transplantation Unit, University Hospital, Padua, Italy.
Abstract
RATIONALE AND OBJECTIVE: Patients with atypical hemolytic uremic syndrome (aHUS) have long been considered ineligible for kidney transplantation (KTx) in several centers due to the high risk of disease recurrence, graft loss and life-threatening complications. The availability of Eculizumab (ECU) has now overcome this problem. However, the best approach towards timing, maintenance schedule, the possibility of discontinuation and patient monitoring has not yet been clearly established. STUDY DESIGN: This is a single center case series presenting our experience with KTx in aHUS. SETTING AND PARTICIPANTS: This study included 26 patients (16 females) with a diagnosis of aHUS, who spent a median of 5.5 years on kidney replacement therapy before undergoing KTx. We compared the aHUS relapse rate in three groups of patients who underwent KTx: patients who received no prophylaxis, patients who underwent plasma exchange, those who received Eculizumab prophylaxis. Complement factor H-related disease was by far the most frequent etiology (n = 19 patients). RESULTS: Untreated patients and patients undergoing pre-KTx plasma exchange prophylaxis had a relapse rate of 0.81 (CI 0.30-1.76) and 3.1 (CI 0.64-9.16) events per 10 years cumulative observation, respectively, as opposed to 0 events among patients receiving Eculizumab prophylaxis. The time between Eculizumab doses was tailored based on classic complement pathway activity (target to < 30%). Using this strategy, 12 patients are currently receiving Eculizumab every 28 days, 5 every 24-25 days, and 3 every 21 days. CONCLUSION: Our experience supports the prophylactic use of Eculizumab in patients with a previous history of aHUS undergoing KTx, especially when complement dysregulation is well documented by molecular biology.
RATIONALE AND OBJECTIVE: Patients with atypical hemolytic uremic syndrome (aHUS) have long been considered ineligible for kidney transplantation (KTx) in several centers due to the high risk of disease recurrence, graft loss and life-threatening complications. The availability of Eculizumab (ECU) has now overcome this problem. However, the best approach towards timing, maintenance schedule, the possibility of discontinuation and patient monitoring has not yet been clearly established. STUDY DESIGN: This is a single center case series presenting our experience with KTx in aHUS. SETTING AND PARTICIPANTS: This study included 26 patients (16 females) with a diagnosis of aHUS, who spent a median of 5.5 years on kidney replacement therapy before undergoing KTx. We compared the aHUS relapse rate in three groups of patients who underwent KTx: patients who received no prophylaxis, patients who underwent plasma exchange, those who received Eculizumab prophylaxis. Complement factor H-related disease was by far the most frequent etiology (n = 19 patients). RESULTS: Untreated patients and patients undergoing pre-KTx plasma exchange prophylaxis had a relapse rate of 0.81 (CI 0.30-1.76) and 3.1 (CI 0.64-9.16) events per 10 years cumulative observation, respectively, as opposed to 0 events among patients receiving Eculizumab prophylaxis. The time between Eculizumab doses was tailored based on classic complement pathway activity (target to < 30%). Using this strategy, 12 patients are currently receiving Eculizumab every 28 days, 5 every 24-25 days, and 3 every 21 days. CONCLUSION: Our experience supports the prophylactic use of Eculizumab in patients with a previous history of aHUS undergoing KTx, especially when complement dysregulation is well documented by molecular biology.