title: Renal function improvement in liver transplant recipients after early everolimus conversion: A clinical practice cohort study in Spain.
abstract: A national, multicenter, retrospective study was conducted to assess the results obtained for liver transplant recipients with conversion to everolimus in daily practice. The study included 477 recipients (481 transplantations). Indications for conversion to everolimus were renal dysfunction (32.6% of cases), hepatocellular carcinoma (HCC; 30.2%; prophylactic treatment for 68.9%), and de novo malignancy (29.7%). The median time from transplantation to conversion to everolimus was 68.7 months for de novo malignancy, 23.8 months for renal dysfunction, and 7.1 months for HCC and other indications. During the first year of treatment, mean everolimus trough levels were 5.4 (standard deviation [SD], 2.7) ng/mL and doses remained stable (1.5 mg/day) from the first month after conversion. An everolimus monotherapy regimen was followed by 28.5% of patients at 12 months. Patients with renal dysfunction showed a glomerular filtration rate (4-variable Modification of Diet in Renal Disease) increase of 10.9 mL (baseline mean, 45.8 [SD, 25.3] versus 57.6 [SD, 27.6] mL/minute/1.73 m(2) ) at 3 months after everolimus initiation (P < 0.001), and 6.8 mL at 12 months. Improvement in renal function was higher in patients with early conversion (<1 year). Adverse events were the primary reason for discontinuation in 11.2% of cases. The probability of survival at 3 years after conversion to everolimus was 83.0%, 71.1%, and 59.5% for the renal dysfunction, de novo malignancy, and HCC groups, respectively. Everolimus is a viable option for the treatment of renal dysfunction, and earlier conversion is associated with better recovery of renal function. Prospective studies are needed to confirm advantages in patients with malignancy.
authors.affiliation: Unidad de Trasplante Hepático, Hospital Universitario Vall d'Hebron, Network Center for Biomedical Research in Hepatic and Digestive Diseases (CIBERehd), Universidad Autónoma Barcelona, Barcelona, Spain.
authors.forename: Itxarone
authors.initials: I
authors.lastname: Bilbao
authors.affiliation: Hospital Gregorio Marañón, CIBERehd, Madrid, Spain.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Salcedo
authors.affiliation: Hospital Virgen del Rocio, Sevilla, Spain.
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Gómez
authors.affiliation: Hospital Doce de Octubre, Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Jimenez
authors.affiliation: Hospital Universitario, Santiago de Compostela, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Castroagudín
authors.affiliation: Hospital de Bellvitge, Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Fabregat
authors.affiliation: Hospital del Rio Hortega, Valladolid, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Almohalla
authors.affiliation: Clinica Universidad de Navarra, CIBERehd, Navarra, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Herrero
authors.affiliation: Hospital Puerta de Hierro, Madrid, Spain.
authors.forename: Valentín
authors.initials: V
authors.lastname: Cuervas-Mons
authors.affiliation: Hospital Universitario, A Coruña, Spain.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Otero
authors.affiliation: Hospital La Fe, CIBERehd, Valencia, Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Rubín
authors.affiliation: Hospital Virgen de la Arrixaca, Murcia, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Miras
authors.affiliation: Hospital Carlos Haya, Málaga, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Rodrigo
authors.affiliation: Hospital Clínico Lozano Blesa, Zaragoza, Spain.
authors.forename: Trinidad
authors.initials: T
authors.lastname: Serrano
authors.affiliation: Hospital Clínic Barcelona, CIBERehd, Barcelona, Spain.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Crespo
authors.affiliation: Hospital Reina Sofía, CIBERehd, Córdoba, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: De la Mata
authors.affiliation: Hospital de Cruces, Bilbao, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Bustamante
authors.affiliation: Hospital Central de Asturias, Oviedo, Spain.
authors.forename: M Luisa
authors.initials: ML
authors.lastname: Gonzalez-Dieguez
authors.affiliation: Hospital Nuestra Señora de la Candelaria, Tenerife, Spain.
authors.forename: Antonia
authors.initials: A
authors.lastname: Moreno
authors.affiliation: Hospital Infanta Cristina, Badajoz, Spain.
authors.forename: Isidoro
authors.initials: I
authors.lastname: Narvaez
authors.affiliation: Novartis Farmacéutica, Barcelona, Spain.
authors.forename: Magda
authors.initials: M
authors.lastname: Guilera
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D016903:Drug Monitoring; D057915:Drug Substitution; D000068338:Everolimus / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D016031:Liver Transplantation / Q000009:adverse effects / Q000401:mortality; D008297:Male; D008875:Middle Aged; D020127:Recovery of Function; D012189:Retrospective Studies; D012307:Risk Factors; D013030:Spain; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D000068338:Everolimus