title: Preconditioning Therapy in ABO-Incompatible Living Kidney Transplantation: A Systematic Review and Meta-Analysis.
abstract: BACKGROUND
  ABO-incompatible (ABOi) kidney transplantation is now an established form of renal replacement therapy, but the efficacy and safety of the different types of preconditioning therapies are unclear. We aimed to synthesize the totality of the published evidence about the effects of any form of preconditioning therapies in living donor ABOi kidney transplantation on graft and patient outcomes.
  
  
  METHODS
  We searched MEDLINE, Embase, and Clinicaltrial.gov databases (inception through June 2015) to identify all studies that described the outcomes of adult living donor ABOi kidney transplantations using any form of preconditioning therapies. Two independent reviewers identified studies, extracted data, and assessed the risk of bias. Data were summarized using the random effects model, and heterogeneity was explored using subgroup analyses. We assessed confidence in the evidence using the Grading of Recommendations Assessment, Development, and Evaluation framework.
  
  
  RESULTS
  Eighty-three studies (54 case reports and case series, 25 cohort, 2 case-control, and 2 registry studies) involving 4810 ABOi transplant recipients were identified. Overall, confidence in the available evidence was low. During a mean follow-up time of 28 (standard deviation [SD], 26.6) months, the overall graft survival for recipients who received immunoadsorption or apheresis was 94.1% (95% confidence interval [95%CI], 88.2%-97.1%) and 88.0% (95% CI, 82.6%-91.8%), respectively. For those who received rituximab or underwent splenectomy, the overall graft survival was 94.5% (95% CI, 91.6%-96.5%) and 79.7% (95% CI, 72.9%-85.1%), respectively. Data on other longer-term outcomes, including malignancy, were sparse.
  
  
  CONCLUSIONS
  Rituximab or immunoadsorption appeared to be promising preconditioning strategies before ABOi kidney transplantation. However, the overall quality of evidence and the confidence in the observed treatment effects are low. The increased use of ABOi kidney transplantation needs to be matched with randomized trials of different types, dosing, and frequency of preconditioning therapies so that this scarce resource can be used most effectively and efficiently.
authors.affiliation: 1 University of New South Wales Medical School, Sydney, NSW, Australia. 2 Sydney School of Public Health, The University of Sydney, Sydney, NSW, Australia. 3 Centre for Transplant and Renal Research, Westmead Hospital, Sydney, NSW, Australia. 4 Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, NSW, Australia. 5 Department of Renal Medicine, Royal Prince Alfred Hospital, Sydney, Australia. 6 Department of Renal Medicine, Sir Charles Gairdner Hospital, Nedlands, Australia. 7 Department of Medicine, University of Otago Christchurch, New Zealand. 8 Cochrane Renal Group, Sydney, Australia. 9 Department of Emergency and Organ Transplantation, University of Bari, Italy. 10 Diaverum Medical Scientific Office and Diaverum Academy, Lund, Sweden.
authors.forename: Phillip
authors.initials: P
authors.lastname: Lo
authors.forename: Ankit
authors.initials: A
authors.lastname: Sharma
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Craig
authors.forename: Kate
authors.initials: K
authors.lastname: Wyburn
authors.forename: Wai
authors.initials: W
authors.lastname: Lim
authors.forename: Jeremy R
authors.initials: JR
authors.lastname: Chapman
authors.forename: Suetonia C
authors.initials: SC
authors.lastname: Palmer
authors.forename: Giovanni F M
authors.initials: GF
authors.lastname: Strippoli
authors.forename: Germaine
authors.initials: G
authors.lastname: Wong
mesh_terms: D000017:ABO Blood-Group System / Q000276:immunology*; D000328:Adult; D001781:Blood Component Removal; D001787:Blood Group Incompatibility / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D006648:Histocompatibility / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013156:Splenectomy; D013997:Time Factors; D019172:Transplantation Conditioning / Q000379:methods; D016896:Treatment Outcome
chemical_list: D000017:ABO Blood-Group System; D007166:Immunosuppressive Agents