The T cell FCXM-negative conversion rates after cumulative doses of 1 1, 2, 3, and 4 g/kg IVIG were 29.4%, 35.3%, 56.3%, and 46.7%, respectively. Conclusions Desensitization of donor-specific antibody-positive renal transplant recipients seems achievable in only a subset of recipients through IVIG dosing (1 g/kg 4) within 1 week after double-filtration plasmapheresis. cell FCXM-negative conversion rate 4 weeks after IVIG administration initiation was 60.3%. The T cell FCXM-negative conversion rates after cumulative doses of 1 1, 2, 3, and 4 g/kg IVIG were 29.4%, 35.3%, 56.3%, and 46.7%, respectively. Conclusions Desensitization of donor-specific antibody-positive renal transplant recipients seems achievable in only a subset of recipients through IVIG dosing (1 g/kg 4) within 1 week after double-filtration plasmapheresis. The T cell FCXM-negative conversion rate resulting from a cumulative IVIG dose of 3 g/kg or greater surpassed that attained via conventional single-dose IVIG (2 g/kg) protocol. This short-term high-dose IVIG desensitization protocol may be an alternative to conventional protocols for recipients with donor-specific antibody. Renal transplantation in patients with end-stage kidney disease improves both duration and quality of life.1-3 Using advanced immunosuppressive therapeutics, the incidence of T cellCmediated rejection can be reduced, and graft survival rates increased.4 However, recipients with donor-specific antibodies (DSA) before renal transplantation (ie, sensitized renal transplantation) show higher rates of antibody-mediated rejection (AMR).5-7 AMR is difficult to prevent with conventional immunosuppressive drugs in DSA-positive patients and is a major cause of renal allograft loss.8 Recently, development in desensitization protocol gives DSA-positive patients more opportunities to receive successful renal transplantation.9,10 In general, 2 protocols are implemented for desensitization before renal transplantation: either high-dose IVIG (2 g/kg) alone or low-dose IVIG (100 mg/kg) in combination with plasma exchange (PE).11-14 Although it is unknown which of these 2 protocols is superior, IVIG plays a key role in desensitization protocols. Rituximab (anti-CD20 antibody) has also proved beneficial in such protocols.15,16 A 4-month regimen of IVIG (2 g/kg per month) is advocated by guidelines for clinical use of IVIG published by public agencies of countries.17-21 IVIG has similarly helped in resolving posttransplantation episodes GSK189254A of steroid-resistant rejection.10 Such rescue therapies generally involve high-dose IVIG (2 g/kg) given as a single dose22 or over the course of several days.23 At present, preferred protocols for preemptive desensitization appear to be GSK189254A transplant center-specific, with limited or no randomized prospective studies to compare efficacies.9 Moreover, there have been no definitive studies on dosages and timing of IVIG administration. In this study, we monitored changes in T cell flow cytometry crossmatch (FCXM) as part of a desensitization protocol in which recipients demonstrating positive T cell FCXM received IVIG (1 g/kg) for 4 days within a 1-week period (total of 4 g/kg) after double-filtration plasmapheresis (DFPP) in preparation for living-donor transplantation. T cell FCXM was measured after each IVIG dose and up to 4 weeks after initiating IVIG administration, allowing us to better establish the timing of conversion and the effectiveness of cumulative IVIG dosing. This super high-dose IVIG-based desensitization protocol may be an alternative to conventional protocols for recipients with DSA. MATERIALS AND METHODS Study Design A phase II/III, open-label, single-arm multicenter prospective trial was performed in Japan between November 2013 and September 2015. The study protocol was approved by the institutional review board of each participating institution and conducted in accordance with the Good Clinical Practice described in the Helsinki Declaration. Patients provided written informed consent before registering in this study. ClinicalTrials.gov Identifier: “type”:”clinical-trial”,”attrs”:”text”:”NCT02032095″,”term_id”:”NCT02032095″NCT02032095. Patient Demographics and Characteristics A total of 17 patients were enrolled for study in preparation for living-donor renal transplantation. Each participant displayed the following: (1) unfavorable T cell complement-dependent cytotoxicity, (2) positive T cell FCXM, and (3) stage-5 chronic kidney disease. Relevant patient characteristics were collected for analysis. Study Protocol Patients showing positive T cell FCXM after 2 rounds of DFPP were administered 1 g/kg GSK189254A per day IVIG (Venoglobulin IH 5%; Japan Blood Products Organization, Tokyo, Japan) for 4 days over a 1-week period. T cell and B cell FCXM were measured the day after each of the 4 IVIG doses. For patients showing positive T cell FCXM after the fourth administration, FCXM was measured weekly until unfavorable conversion was confirmed, for up to 4 weeks after initiating IVIG. The primary study endpoint was Rabbit polyclonal to NPSR1 percentage of patients converting to T cell FCXM-negative status after the fourth IVIG dosage. Patients who prematurely discontinued IVIG dosing were evaluated according to last observation carried forward. Secondary study endpoints were percentage of patients showing conversion to T cell and B cell FCXM-negative status (last observation carried forward) 4 weeks after initiating IVIG administration and percentage of patients converting to T cell and B cell FCXM-negative status.