Pediatric nephrology, dialysis and transplantation Unit
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Interval extension of Eculizumab maintenance treatment in kidney transplanted patients with atypical haemolitic uremic syndrome: an update
Sara Testa1, Patrizia Di Matteo5, Gianluigi Ardissino1, Francesca Tel1, Valentina Capone1, Donata Cresseri2, Stefania Griffini3, Massimo Cugno3, Elena Grovetto4, Silvana Tedeschi4, Giovanni Montini1.
1Pediatric Nephrology, Dialysis and Transplantation Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy; 2Nephrology Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy; 3Internal Medicine, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy; 4Molecular Biology Laboratory, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy; 5Pediatric Department, Policlinico , Università Federico II , Naples, Italy
Center for HUS Prevention, Control and Management.
Introduction: Atypical haemolytic uremic syndrome (aHUS) is a rare, systemic, life-threatening thrombotic microangiopathy (TMA). As many as 70% of aHUS patients have mutations in the genes encoding complement regulatory proteins. Since 2009, Eculizumab, an humanised recombinant monoclonal antibody targeting C5, that prevents the generation of membrane-attack complex C5b-9, has been successfully used in patients with aHUS to prevent relapses. The standard maintenance treatment schedule suggests administration of the drug every two weeks but the best treatment schedule is not yet defined.
Aim: To identify an alternative treatment schedule, also in transplanted patients, based on the biological activity of Eculizumab to improve the patient’s quality of life, reducing the risk of adverse reactions and the development of neutralizing antibodies and, to reduce the heavy costs of the treatment.
Patients and Methods : Kidney transplanted pts for aHUS undergoing Eculizumab treatment in our Center were addressed to an extension of the interval between doses from the standard 2 weeks (wks) to 3 or 4 wks with a strict monitor of global complement activity (AP50 was routinely determined towards a target level of < 25% before subsequent Eculizumab dose) together with a strict home monitoring of indicators of disease reactivation: the presence of blood in the urine performed with dipstick.
Results: Over the last 20 years, a total of 22 patients followed at our Centre for aHUS have undergone 28 KTx (see Table 1 for baseline characteristics). Nine were children at the time of aHUS onset, five of whom were still of pediatric age at KTx and 2 of them were transplanted twice. Eighteen patients undergone Eculizumab treatment: fifteen were addressed to tailored treatment (3 at 3 weeks and 12 at 4 weeks), no aHUS relapses were observed over a cumulative follow up period of 892 mos (mean 59.0 mos/pt); two pts discontinued the treatment because of they have an idiopathic form of the disease or because their genetic
mutations of aHUS are not routinely associated with relapses.; one pts have had a rejection of the kidney transplanted. In 10 transplantations Eculizumab has not been administered because it was not yet available.
Conclusion: Our experience supports the possibility of tailoring Eculizumab schedule for maintenance treatment in kidney transplanted pts with aHUS based on global complement activity. Moreover, this new approach leads to a costs saving of approximately 30%.
Progetto Alice ONLUS.
17:00 - 18:00
|Poster Session 3||Kidney transplant in atypical HUS during Eculizumab Era. A single Center experience||Exhibit-Poster Area|
10:00 - 11:00
|Improving Long-Term Results||Interval extension of Eculizumab maintenance treatment in kidney transplanted patients with atypical haemolitic uremic syndrome: an update <span uk-icon="video-camera"></span>||Bayshore F|