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Tuesday, November 29, 2011

Understanding the Causes of Kidney Transplant Failure: The Dominant Role of Antibody-Mediated Rejection and Nonadherence

Understanding the Causes of Kidney Transplant Failure: The Dominant Role of Antibody-Mediated Rejection and Nonadherence:
We prospectively studied kidney transplants that progressed to failure after a biopsy for clinical indications, aiming to assign a cause to every failure. We followed 315 allograft recipients who underwent indication biopsies at 6 days to 32 years posttransplant. Sixty kidneys progressed to failure in the follow-up period (median 31.4 months). Failure was rare after T-cell–mediated rejection and acute kidney injury and common after antibody-mediated rejection or glomerulonephritis.

Tuberculosis following kidney transplantation: clinical features and outcome. A French multicentre experience in the last 20 years

Tuberculosis following kidney transplantation: clinical features and outcome. A French multicentre experience in the last 20 years:
Background. Kidney transplant recipients are at high risk of opportunistic infection. The aims of this study were to describe the epidemiology, clinical features and prognosis of Tuberculosis (TB) in kidney transplant recipients.
Methods. Retrospective observational study conducted in 14 French transplant centres involving all cases of TB that occurred in kidney transplant recipients between 1986 and 2006.

Epidemiology of Cytomegalovirus Infection After Pancreas Transplantation

Epidemiology of Cytomegalovirus Infection After Pancreas Transplantation: Background. Epidemiology of cytomegalovirus (CMV) infection has not been comprehensively studied after all three types of pancreas transplant (PT) including simultaneous pancreas-kidney transplantation (SPK), pancreas transplantation alone (PTA), and pancreas after kidney transplantation (PAK).
Methods. We evaluated incidence, risk factors, and outcomes of CMV infection after pancreas transplant at our center from January 1, 1998, to December 31, 2009.

Thymoglobulin Versus Basiliximab Induction Therapy for Simultaneous Kidney-Pancreas Transplantation: Impact on Rejection, Graft Function, and Long-Term Outcome

Thymoglobulin Versus Basiliximab Induction Therapy for Simultaneous Kidney-Pancreas Transplantation: Impact on Rejection, Graft Function, and Long-Term Outcome: Background. Thymoglobulin (ATG) and basiliximab induction therapies are used by the majority of centers for pancreas transplantation today. Although both strategies have different mechanisms, there is a paucity of studies comparing them. We compared the efficacy and side effects of both methods in simultaneous pancreas-kidney (SPK) transplantation.
Methods. We analyzed 128 SPKs at our institution between January 2001 and August 2008. Forty-nine patients received basiliximab (40 mg), whereas 79 patients had ATG (5 mg/kg). Graft function, complications, rejection, and survival rates were analyzed.
Results. ATG versus basiliximab therapy was associated with decreased 3-month (6% vs. 21%; P=0.01) and 1-year (14% vs. 27%; P=0.049) rejection rate. Steroid-resistant rejections were decreased with ATG (3%) vs. basiliximab (14%) (P=0.01). In a univariate regression analysis, basiliximab induction was a risk factor for rejection (HR, 7.1; CI, 3.8–13). No differences were observed regarding complications and graft function up to 5 years. ATG versus basiliximab therapy resulted in identical 1-year (90% vs. 93%), 3-year (87% vs. 89%), and 5-year (78% vs. 83%) pancreas survival (P=0.7). No difference was observed in kidney survival after 1 year (99% vs. 98%), 3 years (97% vs. 98%), and 5 years (95% vs. 95%) (P=0.4).
Conclusions. ATG versus basiliximab induction therapy results in decreased acute cellular rejection in the first year after SPK with similar side effects. Long-term graft function and survival are not affected by induction regimen.

Randomized Trial of Dual Antibody Induction Therapy With Steroid Avoidance in Renal Transplantation

Randomized Trial of Dual Antibody Induction Therapy With Steroid Avoidance in Renal Transplantation: Background. Given our previous experience using dual-induction therapy with antithymocyte globulin (ATG)/daclizumab (Dac) (each with fewer doses than if used alone), we chose to compare two distinct dual-induction strategies.
Methods. Single-center, open-label randomized trial of 200 primary kidney transplant recipients was performed: (group I, n=100) ATG/Dac (3 ATG, 2 Dac doses) versus (group II, n=100) ATG/alemtuzumab (1 dose each), with maintenance consisting of reduced tacrolimus dosing (rTd), enteric-coated mycophenolate sodium (EC-MPS), and early corticosteroid withdrawal. One half of standard EC-MPS dosing was targeted in group II to avoid severe leukopenia previously seen with alemtuzumab. The goal in both arms was to achieve rapid and effective lymphocyte depletion while simultaneously allowing reduced maintenance immunosuppression. Primary endpoint was the incidence of biopsy-proven acute rejection (BPAR).
Results. With median follow-up of 38 months, there were no differences in BPAR rates: 14 of 100 vs. 13 of 100 (including borderline) and 10 of 100 vs. 9 of 100 (excluding borderline) in groups I and II, respectively (nonsignificant). Actuarial patient/graft survival at 48 months was 96%/91% in group I vs. 92%/83% in group II (N.S.). Mean estimated glomerular filtration rate (+/-standard error) at 36 months was 72.1+/-3.3 vs. 67.5+/-3.3 in groups I and II (N.S.). Greater incidence of leukopenia occurred in group II at month 1 only (P=0.002). Percentages having EC-MPS withheld/discontinued due to leukopenia, gastrointestinal symptoms, and infection were 12 of 100, 7 of 100, and 0 of 100 in group I vs. 19 of 100, 0 of 100, and 2 of 100 in group II, respectively (P=0.01). Rates of new onset diabetes mellitus after transplantation and infections were equally low in both groups (no lymphoproliferative disorders were observed).
Conclusions. These two distinct dual-induction therapies with rTd, EC-MPS, and planned early corticosteroid withdrawal resulted in favorable rates of BPAR and all secondary outcomes.
(C) 2011 Lippincott Williams & Wilkins, Inc.

Prediction of Delayed Graft Function by Means of a Novel Web-Based Calculator: A Single-Center Experience

Prediction of Delayed Graft Function by Means of a Novel Web-Based Calculator: A Single-Center Experience:
Renal failure persisting after renal transplant is known as delayed graft function (DGF). DGF predisposes the graft to acute rejection and increases the risk of graft loss. In 2010, Irish et al. developed a new model designed to predict DGF risk. This model was used to program a web-based DGF risk calculator, which can be accessed via
http://www.transplantcalculator.com
. The predictive performance of this score has not been tested in a different population. We analyzed 342 deceased-donor adult renal transplants performed in our hospital. Individual and population DGF risk was assessed using the web-based calculator. The area under the ROC curve to predict DGF was 0.710 (95% CI 0.653–0.767, p < 0.001). The “goodness-of-fit” test demonstrates that the DGF risk was well calibrated (p = 0.309). Graft survival was significantly better for patients with a lower DGF risk (5-year survival 71.1% vs. 60.1%, log rank p = 0.036). The model performed well with good discrimination ability and good calibration to predict DGF in a single transplant center. Using the web-based DGF calculator, we can predict the risk of developing DGF with a moderate to high degree of certainty only by using information available at the time of transplantation.