title: Study of kidney function impairment after reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation. A single-center experience.
abstract: Acute renal failure (ARF) is a life-threatening complication after allogeneic stem cell transplantation (Allo-HSCT). Identification of ARF risk factors could be useful to develop preventive strategies for patients at high risk. The goal of this study was to evaluate the incidence and risk factors of ARF after reduced intensity conditioning Allo-HSCT (Allo-RIC). We included 188 consecutive patients who underwent Allo-RIC in our center between January 1999 and December 2006. ARF was defined as a decrease of at least 25% in baseline estimated glomerular filtration rate (GFR) calculated by modification of diet in renal disease (MDRD) equation. Conditioning consisted of fludarabine (Flu) 150 mg/m(2) in combination with busulfan (Bu) 8-10 mg/kg (n = 61), melphalan (Mel) 140 mg/m(2) (n = 115), cyclophosphamide (Cy) 120 mg/kg (n = 7) or low-dose total-body irradiation (TBI) 2 Gy (n = 5). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine A (CsA) alone (n = 3) or in addition to methotrexate (MTX; n = 132) or mycophenolate mofetil (MMF; n = 51). The cumulative incidence of ARF at 1 year was 52% (n = 97 patients) after Allo-RIC. Most cases (86%) occurred within the first 3 months, and the main cause was the administration of CsA (71%). The risk factors associated with ARF in multivariate analysis were: administration of MTX (hazard ratio [HR] 1.9, P =.02), more than 3 lines of therapy prior to Allo-RIC (HR 1.8, P = .01), diabetes mellitus (HR 2.1, P < .01), and GVHD grade III-IV (HR 2.1, P = .015). In multivariate analysis, ARF was an independent risk factor for 1-year nonrelapse mortality (NRM) (HR 3, 95% confidence interval [CI]: 1.5-6, P = .002). Patients who experienced ARF had lower 1-year overall survival (OS; 53% versus 74%, P < .05). ARF is a frequent complication in patients after Allo-RIC, and it has a negative impact on outcome. Identification of ARF risk factors could help to avoid exposure to nephrotoxic drugs during the follow-up in patients at high risk.
authors.affiliation: Clinical Hematology and Hematopoietic Transplantation Division, Autonomous University of Barcelona, Barcelona, Spain. jpinana@santpau.cat
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Piñana
authors.forename: David
authors.initials: D
authors.lastname: Valcárcel
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Martino
authors.forename: Pere
authors.initials: P
authors.lastname: Barba
authors.forename: Estela
authors.initials: E
authors.lastname: Moreno
authors.forename: Anna
authors.initials: A
authors.lastname: Sureda
authors.forename: Monica
authors.initials: M
authors.lastname: Vega
authors.forename: Julio
authors.initials: J
authors.lastname: Delgado
authors.forename: Javier
authors.initials: J
authors.lastname: Briones
authors.forename: Salut
authors.initials: S
authors.lastname: Brunet
authors.forename: Jorge
authors.initials: J
authors.lastname: Sierra
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000209:etiology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002066:Busulfan; D003520:Cyclophosphamide; D016572:Cyclosporine / Q000633:toxicity*; D005260:Female; D005919:Glomerular Filtration Rate; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods* / Q000401:mortality; D006801:Humans; D015994:Incidence; D008297:Male; D008558:Melphalan; D008727:Methotrexate; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives; D011292:Premedication / Q000009:adverse effects; D012307:Risk Factors; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods*; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000031:analogs & derivatives; D014916:Whole-Body Irradiation; D055815:Young Adult
chemical_list: D016572:Cyclosporine; D003520:Cyclophosphamide; D014740:Vidarabine; D002066:Busulfan; D009173:Mycophenolic Acid; C024352:fludarabine; D008558:Melphalan; D008727:Methotrexate