Results of positive cross-match transplantation in African American renal transplant recipients.

Positive cross-match (PXM) renal transplantation has been utilized to address the issue of the increasing demand for transplantation with the shortage of suitable organs. Our primary objective was to analyze the outcomes of African American (AA) PXM renal transplant recipients utilizing AA negative cross-match (NXM) renal transplant recipients as a comparator group. This was a retrospective study consisting of all PXM patients who underwent a desensitization protocol and all AA NXM transplant recipients at the University of Illinois at Chicago from July 2001 to March 2007. We found that AA PXM recipients had significantly lower estimated glomerular filtration rate (eGFR) at 1 year than AA NXM (46.2 vs. 60.6, p = 0.007). AA PXM who experienced acute rejection within the first year were more likely to have an eGFR less than 30 mL/min/1.73 m(2) at 1 year compared to their NXM counterparts (45.5% vs. 12.5%, p = 0.034). Positive cross-match renal transplantation in AA seems to be associated with a high degree of AR and severe renal compromise at 1 year. Larger studies are needed to determine if protocols that are associated with good short-term outcomes in non-AA need to be modified for the AA population.

Limited-dose Daclizumab versus Basiliximab: a comparison of cost and efficacy in preventing acute rejection.

The purpose of this study was to compare the efficacy and cost of the limited-dose Daclizumab regimen to that of the standard-dose Basiliximab regimen. Two antibody induction regimens were compared in patients aged 18 years and older who received renal transplants from January 2002 to September 2003 and completed interleukin (IL)-2R antibody induction with standard-dose Basiliximab (20 mg x 2 doses) or limited-dose Daclizumab (1 mg/kg x 2 doses). The primary outcome measure was the incidence of acute rejection. Secondary outcomes included cost, changes in serum creatinine level, and delayed graft function. Of the 46 patients randomized, 42 patients completed the 6-month follow-up. Mean serum creatinine level at time of discharge was originally higher in the limited-dose Daclizumab group than the standard-dose Basiliximab group (1.89 vs 1.57, respectively). By 1, 3, and 6 months, mean serum creatinine values were similar between both groups, with a trend toward lower mean serum creatinine values in the limited-dose Daclizumab group. The incidence of acute rejection was also similar between the groups (6% vs 7%). The average cost difference between the 2 regimens was approximately $715. This study suggests that a limited-dose Daclizumab regimen may be an efficacious and less costly alternative to the standard-dose Basiliximab regimen for antibody induction therapy following renal transplantation.

Immediate conversion from tacrolimus to cyclosporine in the treatment of posttransplantation diabetes mellitus.

Posttransplantation diabetes (PTDM) is a frequent complication of tacrolimus (TAC)-based immunosuppressive therapy after kidney transplantation. We investigated whether immediate conversion from TAC to Cyclosporine (CSA) could reverse or at least improve new-onset PTDM. Between February 2002 and February 2004, 28 adult kidney transplant recipients maintained on TAC were diagnosed with new-onset PTDM. Eight adult patients with new-onset PTDM were enrolled in the study and converted from TAC to CSA, the remaining 20 patients served as controls and were continued on the TAC-based immunosuppression. The conversion to CSA was performed immediately after establishing the diagnosis of PTDM at an average of 11 months posttransplantation. We did not document any episodes of acute rejection or worsening renal function after conversion. After conversion to CSA, among the 3 patients started on insulin, 1 has come completely off antidiabetic medications, whereas 1 required decreased doses of insulin, and the third has been converted to oral medications. Of the 5 patients originally on oral medications, 3 completely discontinued therapy, whereas the other 2 were well controlled on single-drug therapy at reduced doses. After a mean follow-up of 17 months, in the control group 9 of the 16 patients started on oral antidiabetics ultimately required insulin treatment and no patient could stop antidiabetic or insulin therapy. These findings indicate that conversion from TAC to CSA is a simple, safe, and efficacious way to reverse or at least improve PTDM.

Highly successful living donor kidney transplantation after conversion to negative of a previously positive flow-cytometry cross-match by pretransplant plasmapheresis.

Between July 2001 and November 2003, 16 patients with a positive flow-cytometry crossmatch to their potential living donor for kidney transplant were treated with desensitization protocol based on plasmapheresis and low-dose IVIg starting 1 week before the scheduled transplant. Twelve patients (75%) converted to negative crossmatch and were successfully transplanted. Immunosuppression consisted of induction with thymoglobulin, tacrolimus, mycophenolate mofetil, and steroids. Plasmapheresis and IVIg were continued on alternate days for the first postoperative week. The 1-year patient and graft survival was 100%. The rate of acute rejection was 41% (16% cellular and 25% humoral). All of the rejection episodes resolved with treatment. Combination of plasmapheresis and IVIg allows successful conversion from positive to negative flow-cytometry crossmatch in 75% of cases; after conversion, kidney transplant can be carried out with a high rate of success.

The use of bortezomib as a rescue treatment for acute antibody-mediated rejection: report of three cases and review of literature.

Antibody-mediated rejection (AMR) typically occurs early after transplantation in approximately 5%-7% of recipients. The literature reports suggest that 12%-37% of kidney transplant recipients with acute AMR do not respond to treatment and eventually lose their grafts. The proteasome inhibitor bortezomib is currently approved by the Food and Drug Administration for the treatment of multiple myeloma. It has been demonstrated both in vitro and in vivo to possess apoptotic properties against mature plasma cells. Herein we have described a series of 3 patients with positive cross-matches who developed early AMR after kidney transplantation. Bortezomib rescue treatment was administered after the patients failed to respond to plasmapheresis/intravenous immunoglobulin and splenectomy. All 3 patients responded with full, durable recovery of renal function. In conclusion, bortezomib is useful to treat refractory AMR after kidney transplantation.