Low toxicity regimens in renal transplantation: a country subset analysis of the Symphony study

Abstract

Summary Regional transplant practices may affect clinical outcomes within multinational studies. This study evaluated whether the overall results from the Symphony study can be generalized to the participating countries. De novo adult renal transplant recipients (n = 1645) were randomized to receive standard‐dose cyclosporine, or daclizumab induction plus low‐dose cyclosporine, low‐dose tacrolimus, or low‐dose sirolimus, all in addition to mycophenolate mofetil and steroids. Data for the highest patient‐recruiting countries, Spain (n = 275), Germany (n = 316) and Turkey (n = 258), were compared. Patient transplant characteristics were different among the country subsets; only deceased donors in Spain, more expanded criteria donors in Germany, and mainly living donors in Turkey. Efficacy results for the three countries were consistent with that of the overall study – renal function and biopsy‐proven acute rejection (BPAR) rates were superior with low‐dose tacrolimus. Turkey had higher mean calculated glomerular filtration rate across all treatment groups (60.6–72.2 ml/min) compared with that of Spain (51.1–57.5 ml/min) and Germany (51.3–62.9 ml/min). Spain and Turkey had lower BPAR rates across the four treatment groups compared with the overall study; Germany had much higher rates (21.0–54.2%). These findings confirm the general applicability of the Symphony study results and highlight the importance of inclusion of patients from different geographic origins in randomized clinical trials.

Efficacy and Safety of Tacrolimus-Based Maintenance Regimens in De Novo Kidney Transplant Recipients: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials

“…Six of the 20 primary studies, in which 1 or more treatment arms used Advagraf or Prograf, measured BMI at baseline, with mean values that varied from 21.8 kg/m 2 to 29.2 kg/m 2 [ 17 , 19 , 24 , 31 , 36 , 80 ]. Based on 2 studies, the percentage of patients with diabetes in individual treatment arms was between 6.9% of 390 patients and 28.3% of 212 patients [ 26 , 37 ]. People of White race (11 studies) accounted for between 65.8% of 243 and 95.8% of 309 patients in individual treatment arms [ 17 , 19 , 24 – 26 , 28 , 29 , 32 , 35 , 37 , 80 ].…”

Immunological induction with thymoglobulin: reduction in the number of doses in renal transplant from deceased donor

“…Recently, the Transplantation Service of the Hospital Israelita Albert Einstein adopted the strategy of using lower doses of calcineurin inhibitor, aiming at intermediary levels. Another difficulty in comparing the renal function results of each of the groups evaluated here with those of other studies is that only a few of them defined renal function as a primary outcome (23) . Another important outcome evaluated in this study was CMV infection.…”

Reduced-dose Cyclosporine with Mycophenolate Mofetil and Prednisone Significantly Improves the Long-term Glomerular Filtration Rate and Graft Survival

“…The authors believe that optimizing exposure to mycophenolate mofetil through therapeutic drug monitoring can improve the allograft function in patients receiving a cyclosporine-based regimen. A subset analysis of the Symphony study showed that patients from different countries exhibit different renal functions (26). In the Symphony study, less than 2% of the patients were black, whereas in the United States in 2006, more than 35% of patients who were awaiting kidney transplantation were black.…”