Eculizumab for Prevention of Antibody-Mediated Rejection in Blood Group-Incompatible Renal Transplantation.

Antibody-mediated rejection (AMR) is one of the leading causes of allograft failure especially in patients undergoing ABO-incompatible (ABOi) renal transplantation. We hypothesized that complement inhibition with eculizumab, a C5 inhibitor, would protect against AMR and maintain graft function in ABOi renal transplant recipients. Four patients undergoing living donor kidney transplant from ABOi donors were treated with a 9-week eculizumab course without therapeutic plasma exchange, intravenous immunoglobulin, or splenectomy. All patients had successful transplants and have normal graft function at the time of last follow-up. There were no cases of AMR or acute cellular rejection. Of note, 2 patients were transplanted despite persistent ABO antibody titers of 1:32, conventionally considered a contraindication to proceed in standard protocols. Eculizumab is a promising option to prevent AMR with ABOi renal transplantation without the need for splenectomy, post-transplant therapeutic plasma exchange, and intravenous immunoglobulin. Future multicenter studies are needed to determine long-term efficacy and safety.

A novel and personalized rehabilitation program for obese kidney transplant recipients.

INTRODUCTION: Physical rehabilitation programs for kidney transplant recipients are not routinely personalized to patients' physical and emotional health, which could result in a potentially limited health impact, shorter-term participation, and an overall low success rate. MATERIALS AND METHODS: We conducted an internal review board-approved randomized prospective study involving a 12-month supervised multidisciplinary rehabilitation program (GH method) initiated after kidney transplantation in obese recipients (body mass index >30). The new method incorporates 3 major components: physical exercise, behavioral interventions, and nutritional guidance. We compared 9 patients who underwent supervised rehabilitation with 8 patients who underwent standard care. Patients were followed up after the start of the intervention, and multiple assessments were performed. RESULTS: The adherence to training and follow-up was 100% in the intervention group, compared with 25% at 12 months in the control group. There was a trend for a higher glomerular filtration rate in the intervention group compared with the control group (55.5 ± 18.6 mL/min/1.73 m(2) vs 38.8 ± 18.9 mL/min/1.73 m(2), P = .06). The quality of life (SF-36) mean score improved more in the intervention group compared with the control group (583 ± 13 vs 436 ± 22, P = .008). There was a significantly higher employment rate in the intervention group, 77.7% at 12 months compared with 12.5% in the control group (P = .02). CONCLUSIONS: Our preliminary results suggest that this comprehensive approach to physical rehabilitation can improve adherence, kidney function, quality of life, and employment rate for obese patients after kidney transplantation.

Conversion from twice-daily tacrolimus to once-daily extended release tacrolimus (LCPT): the phase III randomized MELT trial.

Phase III noninferiority trial examining efficacy and safety of converting stable renal transplant recipients from twice-daily tacrolimus to a novel extended-release once-daily tacrolimus formulation (LCPT) with a controlled agglomeration technology. Controls maintained tacrolimus twice daily. The primary efficacy endpoint was proportion of patients with efficacy failures (death, graft failure, locally read biopsy-proven acute rejection [BPAR], or loss to follow-up) within 12 months. Starting LCPT dose was 30% lower (15% for blacks) than preconversion tacrolimus dose; target trough levels were 4-15 ng/mL. A total of 326 patients were randomized; the mITT population (n = 162 each group) was similar demographically in the two groups. Mean daily dose of LCPT was significantly (p < 0.0001) lower than preconversion tacrolimus dose at each visit; mean trough levels between groups were similar. There were four efficacy failures in each group; safety outcomes were similar between groups. Frequency of premature study drug discontinuation was LCPT: 12% versus tacrolimus twice daily: 5% (p = 0.028). LCPT demonstrated noninferiority to tacrolimus twice daily in efficacy failure rates. LCPT may offer a safe and effective alternative for converting patients to a once-daily formulation. Compared to currently available tacrolimus formulation, LCPT requires lower doses to achieve target trough levels.

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.