Tuesday, June 26, 2012

Alemtuzumab Induction Therapy in Kidney Transplantation: A Systematic Review and Meta-Analysis

Alemtuzumab Induction Therapy in Kidney Transplantation: A Systematic Review and Meta-Analysis: Background: Alemtuzumab (MabCampath or Campath; Genzyme, Cambridge, MA) is a CD52-specific monoclonal antibody that causes profound and sustained lymphocyte depletion. Its use as an induction therapy in organ transplantation is increasing. Since our last systematic review in 2006, where we identified the need for good-quality randomized controlled trials (RCTs), several RCTs have been published that examine its efficacy and safety in kidney transplantation. The aim of this study was to evaluate the current evidence for alemtuzumab induction therapy in kidney transplantation.

Thursday, June 14, 2012

Using Donor-Specific Antibodies to Monitor the Need for Immunosuppression

Using Donor-Specific Antibodies to Monitor the Need for Immunosuppression: Background: Experience with tolerance protocols has shown that none is perfect and that each escape from tolerance must be identified early to prevent graft failure. In addition, some test is needed for patients who are weaned off immunosuppression (IS) to forewarn of weaning failure. The usual measures of function—such as serum creatinine levels—are not sensitive enough to detect rejection in a timely manner.
Methods: A study was carried out on 72 patients who received living-donor kidney transplants with clonal deletion protocol (total lymphoid irradiation or bortezomib), and followed with reduced doses of maintenance IS. Every month or every 2 months, a test was performed for donor-specific antibodies (DSA) using Luminex mixed and/or single antigen beads.
Results: After transplantation, DSA developed in 17% of the patients at 6 months, 41% at 1 year, and 57% at 2 years, with 95% confidence limits of 10%, 28%; 30%, 55%; and 44%, 71%, respectively. Fifty-three percent of patients weaned IS to less than 10 mg prednisone daily experienced DSA within 3 months. Furthermore, prednisone dose (per 2.5 mg) and years after transplantation were inversely associated with DSA production (risk ratio 0.92 [95% confidence limits: 0.85, 0.99], and 0.70 [0.49, 1.00]).
Conclusions: DSA monitoring is highly effective for detecting escape from tolerance and reemergence of the immune response in weaned patients. DSA appearance was inversely proportional to the level of maintenance drugs in the weaning process. Measurement of DSA on a monthly basis is adequate for detection of the change in immune reactivity.

Review of Cytomegalovirus Infection Findings With Mammalian Target of Rapamycin Inhibitor-Based Immunosuppressive Therapy in De Novo Renal Transplant Recipients

Review of Cytomegalovirus Infection Findings With Mammalian Target of Rapamycin Inhibitor-Based Immunosuppressive Therapy in De Novo Renal Transplant Recipients: Cytomegalovirus (CMV) infection and disease are major complications in the renal transplant recipient. The occurrence of CMV is associated with acute rejection, allograft dysfunction, significant end-organ disease, and mortality. Several clinical studies have indicated that the use of certain immunosuppressive drugs can delay the reconstitution of CMV-specific cell-mediated immune responses, thereby leading to uncontrolled CMV replication. Accumulating evidence indicates, however, that the use of the mammalian target of rapamycin (mTOR) inhibitors, sirolimus, and everolimus, may decrease the incidence and severity of CMV infection in renal transplant recipients. The purpose of this article is to review CMV infection data from randomized clinical trials that investigated the use of sirolimus- and everolimus-based treatment regimens in de novo renal transplantation. The mTOR inhibitor clinical trials included were primarily identified using biomedical literature database searches, with additional studies added at the authors’ discretion. This review will summarize these studies to discuss whether mTOR inhibitor-based immunosuppressive therapy can reduce the magnitude of CMV-related complications in the de novo renal transplantation setting.

Monday, June 4, 2012

Very Early Recurrence of Anti-Phospholipase Asub2/sub Receptor-Positive Membranous Nephropathy After Transplantation

Very Early Recurrence of Anti-Phospholipase Asub2/sub Receptor-Positive Membranous Nephropathy After Transplantation

Comparison of C4d Detection on Erythrocytes and PTC-C4d to Histological Signs of Antibody-Mediated Rejection in Kidney Transplantation

Comparison of C4d Detection on Erythrocytes and PTC-C4d to Histological Signs of Antibody-Mediated Rejection in Kidney Transplantation

A Novel ELISPOT Assay to Quantify HLA-Specific B Cells in HLA-Immunized Individuals

A Novel ELISPOT Assay to Quantify HLA-Specific B Cells in HLA-Immunized Individuals

CMV Late Phase-Induced mTOR Activation Is Essential for Efficient Virus Replication in Polarized Human Macrophages

CMV Late Phase-Induced mTOR Activation Is Essential for Efficient Virus Replication in Polarized Human Macrophages

Conversion From Cyclosporine to Everolimus at 4.5 Months Posttransplant: 3-Year Results From the Randomized ZEUS Study

Conversion From Cyclosporine to Everolimus at 4.5 Months Posttransplant: 3-Year Results From the Randomized ZEUS Study