Thursday, January 30, 2014

Randomized Trial of Three Induction Antibodies in Kidney Transplantation: Long-Term Results

Transplantation - Published Ahead-of-Print Randomized Trial of Three Induction Antibodies in Kidney Transplantation: Long-Term Results

Background: In searching for an optimal induction regimen, we conducted two separate randomized trials of 38 living donor and 90 deceased donor adult, primary kidney transplant recipients comparing antithymocyte globulin (Thymoglobulin) (group A, N=43) versus alemtuzumab (group B, N=43) versus daclizumab (group C, N=42), using exactly the same three treatment arms in each trial. Methods: For the purpose of maximizing statistical power, results from the two randomized trials were combined. Groups A and C received standard maintenance dosing with tacrolimus (TAC), mycophenolate mofetil (MMF), and corticosteroids. Because of intense lymphodepletion expected with alemtuzumab use (and hoped-for achievement of a truer immunoregulatory state), group B received lower TAC and MMF dosing and corticosteroid avoidance. Long-term target TAC trough level and MMF dosing were 5 to 7 ng/mL and 1,000 mg b.i.d. in groups A and C; 4 to 6 ng/mL and 500 mg b.i.d. in group B. Results: With median follow-up of 95 months, biopsy-proven cute rejection incidence was similar in the three groups (8/43, 14/43, and 12/42, P=0.34), but biopsy-proven chronic allograft injury incidence was significantly higher in group B (19/43) in comparison with groups A (9/43) and C (7/42) combined (P=0.0008). Mean calculated creatinine clearance was significantly lower in group B versus the average of groups A and C means throughout 60 months posttransplant (62.9+/-4.2 vs. 83.6+/-6.9 and 79.8+/-5.9 at 60 months, P=0.01), and death-censored graft failure was significantly higher in group B (13/43) versus groups A (5/43) and C (5/42) combined (P=0.009). Total infection and new-onset diabetes after transplant rates were not significantly different. Ad hoc analysis suggested that the inferior results in group B were specifically a result of reduced dosing and greater withholding of TAC and MMF occurring in that group. Conclusions: Long-term results clearly indicate inferior clinical outcomes in group B. (C) 2014 by Lippincott Williams & Wilkins


http://pdfs.journals.lww.com/transplantjournal/9000/00000/Randomized_Trial_of_Three_Induction_Antibodies_in.98321.pdf

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Saturday, January 25, 2014

Influence of Anemia on Patient and Graft Survival After Renal Transplantation: Results From the French DIVAT Cohort

Transplantation - Most Popular Articles Influence of Anemia on Patient and Graft Survival After Renal Transplantation: Results From the French DIVAT Cohort

imageBackground and ObjectivesContradictory results are reported concerning the influence of anemia on patient and graft survival after renal transplantation. Assuming that level of renal function and anemia are strongly correlated, posttransplantation anemia (PTA) may have a different impact depending on the stage of chronic kidney disease (CKD). MethodsThis study is a retrospective multicenter analysis using the DIVAT French database. The prevalence, risk factors, and influence of 12-month PTA (World Health Organization's definition) on patient and graft survival were analyzed according to CKD stage (Modification of Diet in Renal Disease equation). ResultsThe prevalence of 12-month PTA in our cohort of 4217 patients was 41.1%. Multivariate analysis demonstrated that worse renal function, donor age, period of transplantation, induction therapy, and mTOR inhibitors were significant risk factors for PTA. Posttransplantation anemia was a significant risk factor for all-cause mortality in CKD stages 1 to 2T (hazard ratio, 2.39; 95% confidence interval, 1.99–4.40) and 3T (hazard ratio, 1.52; 95% confidence interval, 1.08–2.15) and for cardiovascular mortality only on CKD stages 1T and 2T. In renal transplant recipients with CKD stages 4 to 5T, patient and graft survival were similar in patients with versus without anemia. Graft survival was not influenced by PTA, whatever the CKD stage. ConclusionsPosttransplantation anemia is associated with decreased patient survival only in CKD stages 1T, 2T, and 3T. Posttransplantation anemia has no influence on graft survival regardless of CKD stage.


http://journals.lww.com/transplantjournal/Fulltext/2014/01270/Influence_of_Anemia_on_Patient_and_Graft_Survival.10.aspx


Monday, January 20, 2014

Cardiac Response to Early Conversion from Calcineurin Inhibitor to Everolimus in Renal Transplant Recipients: An Echocardiographic Substudy of the Randomized Controlled CENTRAL Trial

Transplantation - Current Issue Cardiac Response to Early Conversion from Calcineurin Inhibitor to Everolimus in Renal Transplant Recipients: An Echocardiographic Substudy of the Randomized Controlled CENTRAL Trial

imageBackgroundCalcineurin inhibitors are associated with adverse cardiac effects. Mammalian target of rapamycin inhibitors have been reported to have beneficial effects on cardiac function. We used advanced echocardiographic techniques in a randomized controlled trial to examine cardiac responses to an everolimus-based arm versus a calcineurin inhibitor–based arm in de novo kidney transplant recipients. MethodsThis was a substudy of the Certican Nordic Trial in Renal Transplantation study, a randomized controlled trial on safety and efficacy of early (week 7 after renal transplantation) conversion from cyclosporine A (CsA) to everolimus versus continued CsA during 1-year follow-up. A total of 44 patients (66% men; median [range] age, 61 [28–78] years) were included. All participants had a complete echocardiographic evaluation at baseline and at 1-year follow-up. ResultsLeft ventricular (LV) systolic function, LV mass, left atrial volumes, and blood pressure response did not differ between groups during 1-year follow-up. There was, however, a difference between the groups in change in peak early mitral velocity after 1 year (P=0.02), and E/e′ ratio trended higher in the everolimus group (P=0.09). ConclusionsEarly conversion from CsA-based to everolimus-based immunosuppressive treatment in de novo renal transplant recipients caused marginal changes in LV diastolic function but no effect on LV systolic function or LV mass.


http://journals.lww.com/transplantjournal/Fulltext/2014/01270/Cardiac_Response_to_Early_Conversion_from.12.aspx

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Influence of Anemia on Patient and Graft Survival After Renal Transplantation: Results From the French DIVAT Cohort

Transplantation - Current Issue Influence of Anemia on Patient and Graft Survival After Renal Transplantation: Results From the French DIVAT Cohort

imageBackground and ObjectivesContradictory results are reported concerning the influence of anemia on patient and graft survival after renal transplantation. Assuming that level of renal function and anemia are strongly correlated, posttransplantation anemia (PTA) may have a different impact depending on the stage of chronic kidney disease (CKD). MethodsThis study is a retrospective multicenter analysis using the DIVAT French database. The prevalence, risk factors, and influence of 12-month PTA (World Health Organization's definition) on patient and graft survival were analyzed according to CKD stage (Modification of Diet in Renal Disease equation). ResultsThe prevalence of 12-month PTA in our cohort of 4217 patients was 41.1%. Multivariate analysis demonstrated that worse renal function, donor age, period of transplantation, induction therapy, and mTOR inhibitors were significant risk factors for PTA. Posttransplantation anemia was a significant risk factor for all-cause mortality in CKD stages 1 to 2T (hazard ratio, 2.39; 95% confidence interval, 1.99–4.40) and 3T (hazard ratio, 1.52; 95% confidence interval, 1.08–2.15) and for cardiovascular mortality only on CKD stages 1T and 2T. In renal transplant recipients with CKD stages 4 to 5T, patient and graft survival were similar in patients with versus without anemia. Graft survival was not influenced by PTA, whatever the CKD stage. ConclusionsPosttransplantation anemia is associated with decreased patient survival only in CKD stages 1T, 2T, and 3T. Posttransplantation anemia has no influence on graft survival regardless of CKD stage.


http://journals.lww.com/transplantjournal/Fulltext/2014/01270/Influence_of_Anemia_on_Patient_and_Graft_Survival.10.aspx

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Randomized Controlled Trial Comparing Hand-Assisted Retroperitoneoscopic Versus Standard Laparoscopic Donor Nephrectomy

Transplantation - Current Issue Randomized Controlled Trial Comparing Hand-Assisted Retroperitoneoscopic Versus Standard Laparoscopic Donor Nephrectomy

imageBackgroundLaparoscopic donor nephrectomy (LDN) has become the gold standard for live-donor nephrectomy, as it results in a short convalescence time and increased quality of life. However, intraoperative safety has been debated, as severe complications occur incidentally. Hand-assisted retroperitoneoscopic donor nephrectomy (HARP) is an alternative approach, combining the safety of hand-guided surgery with the benefits of endoscopic techniques and retroperitoneal access. We assessed the best approach to optimize donors' quality of life and safety. MethodsIn two tertiary referral centers, donors undergoing left-sided nephrectomy were randomly assigned to HARP or LDN. Primary endpoint was physical function, one of the dimensions of the Short Form-36 questionnaire on quality of life, at 1 month postoperatively. Secondary endpoints included intraoperative events and operation times. Follow-up was 1 year. ResultsIn total, 190 donors were randomized. Physical function at 1 month follow-up did not significantly differ between groups (estimated difference, 1.79; 95% confidence interval, −4.1 to 7.68; P=0.55). HARP resulted in significantly shorter skin-to-skin time (mean, 159 vs. 188 min; P<0.001), shorter warm ischemia time (2 vs. 5 min; P<0.001) and a lower intraoperative event rate (5% vs. 11%, P=0.117). Length of stay (both 3 days; P=0.135) and postoperative complication rate (8% vs. 8%; P=1.00) were not significantly different. Potential graft-related complications did not significantly differ (6% vs. 13%; P=0.137). ConclusionsCompared with LDN, left-sided HARP leads to similar quality of life, shorter operating time, and warm ischemia time. Therefore, we recommend HARP as a valuable alternative to the laparoscopic approach for left-sided donor nephrectomy.


http://journals.lww.com/transplantjournal/Fulltext/2014/01270/Randomized_Controlled_Trial_Comparing.9.aspx

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Friday, January 10, 2014

Pulsatile Perfusion Reduces the Risk of Delayed Graft Function in Deceased Donor Kidney Transplants, Irrespective of Donor Type and Cold Ischemic Time

Transplantation - Published Ahead-of-Print Pulsatile Perfusion Reduces the Risk of Delayed Graft Function in Deceased Donor Kidney Transplants, Irrespective of Donor Type and Cold Ischemic Time

Background: The role of pulsatile perfusion (PP) across different cold ischemic times (CIT) within different donor groups is unclear. This study examined the association of PP with delayed graft function (DGF) in all (n=94,709) deceased donor kidney transplants in the US between 2000 and 2011, as a function of CIT and donor type. Methods: Using the Scientific Registry of Transplant Recipients data, all adult standard criteria donors (SCD, n=71,192), expanded criteria donors (ECD, n=15,122), and donors after circulatory death (DCD, n=8,395) kidney transplant recipients were identified. Within each donor group, transplants were stratified based on duration of CIT: 0 to 6 hours, 6.1 to 12 hours, 12.1 to 18 hours, 18.1 to 24 hours, 24.1 to 30 hours, 30.1 to 36 hours, and greater than 36 hours. Within each group, the odds of DGF with and without PP was determined after adjusting for donor, recipient, and transplant factors, including a propensity score for the likelihood of PP use, and clustering on transplant center using multivariable logistic regression. Results: When stratified by donor type and CIT, the adjusted odds of DGF were lower with PP across all CIT in SCD transplants, when CIT was greater than 6 hours in ECD transplants, and when CIT was between 6 and 24 hours in DCD transplants. CIT was independently associated with a greater risk of DGF irrespective of storage method, but this effect was substantially modified by PP. Conclusion: PP is associated with a reduced risk of DGF irrespective of donor type and CIT. Although PP modifies the impact of CIT on the risk of DGF, it does not eliminate its association with DGF, suggesting the optimal strategy to reduce DGF is to minimize CIT and utilize PP in all deceased donor transplants. (C) 2014 by Lippincott Williams & Wilkins


http://pdfs.journals.lww.com/transplantjournal/9000/00000/Pulsatile_Perfusion_Reduces_the_Risk_of_Delayed.98339.pdf

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Tuesday, January 7, 2014

Alemtuzumab and Sirolimus in Renal Transplantation: Six-Year Results of a Single-Arm Prospective Pilot Study

AJT - Early Alemtuzumab and Sirolimus in Renal Transplantation: Six-Year Results of a Single-Arm Prospective Pilot Study

mTOR inhibitors avoid calcineurin nephrotoxicity, but sirolimus de novo is associated with unacceptable side effects and higher rejection rates. We have investigated a modified strategy: alemtuzumab induction with tacrolimus and mycophenolate maintenance, switching from tacrolimus to sirolimus at 6 months and stopping mycophenolate at 12 months. Here, we report the 6-year follow-up of 30 patients prospectively recruited to this single-arm pilot study and compare outcomes to a matched contemporaneous control group of 30 patients who received standard induction and calcineurin-inhibitor-based immunosuppression. Six-year patient and graft survival were 83% and 80% (alemtuzumab) versus 77% and 70% (control). Rejection rates in the first 6 months were similar in alemtuzumab (6.6%) and control groups (10%). A higher than expected incidence of rejection in the alemtuzumab group following cessation of mycophenolate at 1 year (17%) was mitigated in later patients by retaining low dose mycophenolate. Mean eGFR was higher in the alemtuzumab group at all time points but not significantly (p = 0.16). Tacrolimus levels in the first 6 months were significantly higher in the contemporaneous control group (p < 0.001). Alemtuzumab induction with initial treatment with tacrolimus enables conversion to sirolimus without the side effects and incidence of acute rejection seen in earlier protocols.




http://onlinelibrary.wiley.com/resolve/doi?DOI=10.1111%2Fajt.12572