Preconditioning Therapy in ABO-Incompatible Living Kidney Transplantation: A Systematic Review and Meta-Analysis

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.