| 1. |
- Cippà, Pietro E, et al.
(författare)
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Risk Stratification for Rejection and Infection after Kidney Transplantation.
- 2015
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Ingår i: Clinical Journal of the American Society of Nephrology. - 1555-905X. ; 10:12, s. 2213-2220
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Tidskriftsartikel (refereegranskat)abstract
- Definition of individual risk profile is the first step to implement strategies to keep the delicate balance between under- and overimmunosuppression after kidney transplantation.
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| 2. |
- Demirbas, Alper, et al.
(författare)
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Low toxicity regimens in renal transplantation: a country subset analysis of the Symphony study
- 2009
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Ingår i: Transplant International. - : Frontiers Media SA. - 1432-2277 .- 0934-0874. ; 22:12, s. 1172-1181
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Tidskriftsartikel (refereegranskat)abstract
- P>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.
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| 3. |
- Ekberg, Henrik, et al.
(författare)
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Cyclosporine, tacrolimus and sirolimus retain their distinct toxicity profiles despite low doses in the Symphony study.
- 2010
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Ingår i: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. - : Oxford University Press (OUP). - 1460-2385. ; 25, s. 2004-2010
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Reducing side effects of immunosuppressive regimens has become a priority in transplantation medicine because of the large number of patients and grafts that succumb to infection in the short term and cardiovascular disease in the long term. The Symphony study was a 12-month prospective, randomized, open-label, multi-centre, four parallel arm study that aimed to evaluate the safety and efficacy of low-dose immunosuppressive regimens compared with a standard-dose regimen in renal transplant recipients. This sub-analysis focuses on specific toxicities observed with the low-dose regimens. METHODS: Adult patients (n = 1645) scheduled to undergo renal transplantation received low-dose cyclosporine (CsA), tacrolimus (Tac) or sirolimus (SRL) in addition to daclizumab induction or standard-dose cyclosporine without induction. All patients received mycophenolate mofetil and corticosteroids. We evaluated the incidence of adverse events (AEs), tested specific group differences and assessed the relationship of selected AEs with drug levels. RESULTS: The four arms had similar incidences of AEs, but serious AEs were more common with low-dose SRL and led to more discontinuations. Infections were the most common AEs, with the highest incidence in the standard-dose CsA group, in particular, cytomegalovirus (CMV) infections. Low-dose Tac had the most reports of new-onset diabetes, leucopenia and diarrhoea. Low-dose SRL negatively influenced triglycerides, wound healing, lymphocele and anaemia. We found only weak relationships between specific AEs and drug levels. CONCLUSIONS: Despite the low doses, CsA, Tac and SRL retained distinct and different toxicity profiles. These findings may be of relevance for tailoring specific immunosuppressive regimens to patients with particular needs.
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| 4. |
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| 5. |
- Ekberg, Henrik, et al.
(författare)
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Relationship of Tacrolimus Exposure and Mycophenolate Mofetil Dose With Renal Function After Renal Transplantation.
- 2011
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Ingår i: Transplantation. - 1534-6080. ; 92, s. 82-87
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION.: The most common immunosuppressive treatment in de novo renal transplantation is a triple regimen that includes tacrolimus, mycophenolate mofetil (MMF) and corticosteroids, and that may also include antibody induction. Whether nephrotoxicity is an issue with tacrolimus at the currently used dosages remains an open question. METHODS.: We pooled data from three large, randomized, de novo renal transplantation studies (Symphony, Fixed Dose Concentration Controlled [FDCC], and OptiCept) that used variations of the triple regimen with respect to tacrolimus target levels, MMF dosing, and antibody induction. We used multivariate linear regression to explore the relationship of renal function at 1 year after transplantation (estimated glomerular filtration rate) with tacrolimus levels and MMF dose measured over the previous 6 months. The model included also a series of possible confounders. RESULTS.: The analysis population consisted of 998 patients. On average, tacrolimus levels were in a range considered low (mean±standard deviation 7.2±2.54 ng/mL), and MMF dose was 1.5±0.61 g/day. Lower tacrolimus levels and higher MMF doses were associated with significantly better renal function. There were other variables associated with renal function, most notably acute rejection, donor age, and delayed graft function. Subanalyses in each of the three studies gave a consistent picture. There was no overt difference in the effect sizes when patients with stage II (estimated glomerular filtration rate 60-89 mL/min) or stage III (30-59 mL/min) chronic kidney disease were assessed separately. CONCLUSION.: Tacrolimus seems to have a moderate but consistent nephrotoxic effect even in modern efficient immunosuppressive regimens where it is used at lower doses than in previous years.
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| 6. |
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| 7. |
- Frei, Ulrich, et al.
(författare)
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Acute rejection in low-toxicity regimens: clinical impact and risk factors in the Symphony study
- 2010
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Ingår i: Clinical Transplantation. - : Wiley. - 1399-0012 .- 0902-0063. ; 24:4, s. 500-509
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Tidskriftsartikel (refereegranskat)abstract
- The Symphony study assessed whether mycophenolate mofetil (MMF)-based regimens containing reduced doses of adjunct immunosuppressants could reduce toxicity while maintaining efficacy. Here, we examined the impact of acute rejection and associated risk factors. The incidence of biopsy-proven acute rejection in the low-dose tacrolimus group was approximately half that of the standard-dose cyclosporine and low-dose cyclosporine groups, and a third of that in the low-dose sirolimus group. The low-dose cyclosporine group had more severe rejection episodes (>= grade II) compared with other groups. Acute rejection was associated with a 10 mL/min glomerular filtration rate (GFR) reduction and a 5.3% absolute increase in graft loss at 12 months. Overall, the highest GFR was found in both rejecters and non-rejecters receiving low-dose tacrolimus, both in an intent-to-treat analysis and in patients successfully treated according to the protocol. In Cox regression models, human leukocyte antigen (HLA) mismatches and expanded criteria donors increased the acute rejection risk, while recipient age, living related donor, and MMF dose were associated with a reduced risk. Acute rejection was associated with worse outcome but did not entirely explain the differences among the treatment groups. The 2 g MMF plus low-dose tacrolimus combination appears to be the most efficient of all regimens examined regardless of acute rejection.
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