PMID- 20106825
OWN - NLM
STAT- MEDLINE
DCOM- 20100914
LR  - 20191210
IS  - 1460-2385 (Electronic)
IS  - 0931-0509 (Linking)
VI  - 25
IP  - 6
DP  - 2010 Jun
TI  - Cyclosporine, tacrolimus and sirolimus retain their distinct toxicity profiles 
      despite low doses in the Symphony study.
PG  - 2004-10
LID - 10.1093/ndt/gfp778 [doi]
AB  - 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.
FAU - Ekberg, Henrik
AU  - Ekberg H
AD  - Department of Nephrology and Transplantation, Lund University, University 
      Hospital, Malmo, Sweden. henrik.ekberg@med.lu.se
FAU - Bernasconi, Corrado
AU  - Bernasconi C
FAU - Noldeke, Jana
AU  - Noldeke J
FAU - Yussim, Alexander
AU  - Yussim A
FAU - Mjornstedt, Lars
AU  - Mjornstedt L
FAU - Erken, Ugur
AU  - Erken U
FAU - Ketteler, Markus
AU  - Ketteler M
FAU - Navratil, Pavel
AU  - Navratil P
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
DEP - 20100126
PL  - England
TA  - Nephrol Dial Transplant
JT  - Nephrology, dialysis, transplantation : official publication of the European 
      Dialysis and Transplant Association - European Renal Association
JID - 8706402
RN  - 0 (Adrenal Cortex Hormones)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Calcineurin Inhibitors)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Immunosuppressive Agents)
RN  - 83HN0GTJ6D (Cyclosporine)
RN  - CUJ2MVI71Y (Daclizumab)
RN  - HU9DX48N0T (Mycophenolic Acid)
RN  - W36ZG6FT64 (Sirolimus)
RN  - WM0HAQ4WNM (Tacrolimus)
SB  - IM
MH  - Adrenal Cortex Hormones/administration & dosage
MH  - Antibodies, Monoclonal/administration & dosage
MH  - Antibodies, Monoclonal, Humanized
MH  - Calcineurin Inhibitors
MH  - Cyclosporine/administration & dosage/*adverse effects
MH  - Daclizumab
MH  - Delayed Graft Function/etiology
MH  - Female
MH  - Humans
MH  - Immunoglobulin G/administration & dosage
MH  - Immunosuppressive Agents/administration & dosage/*adverse effects
MH  - Infections/etiology
MH  - *Kidney Transplantation/adverse effects/immunology/physiology
MH  - Lipid Metabolism/drug effects
MH  - Male
MH  - Middle Aged
MH  - Mycophenolic Acid/administration & dosage/analogs & derivatives
MH  - Prospective Studies
MH  - Sirolimus/administration & dosage/*adverse effects
MH  - Tacrolimus/administration & dosage/*adverse effects
MH  - Treatment Outcome
EDAT- 2010/01/29 06:00
MHDA- 2010/09/15 06:00
CRDT- 2010/01/29 06:00
PHST- 2010/01/29 06:00 [entrez]
PHST- 2010/01/29 06:00 [pubmed]
PHST- 2010/09/15 06:00 [medline]
AID - gfp778 [pii]
AID - 10.1093/ndt/gfp778 [doi]
PST - ppublish
SO  - Nephrol Dial Transplant. 2010 Jun;25(6):2004-10. doi: 10.1093/ndt/gfp778. Epub 
      2010 Jan 26.