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Tytuł:
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A 50% reduction in cyclosporine exposure in stable renal transplant recipients: renal function benefits.
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Autorzy:
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Etienne I; Department of Nephrology, Rouen University Hospital, and Inserm CIC 0204, Institute of Biomedical Research, University of Rouen, Rouen, France. />Toupance O
Bénichou J
Thierry A
Al Najjar A
Hurault de Ligny B
Le Meur Y
Westeel PF
Marquet P
François A
Hellot MF
Godin M
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Źródło:
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Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association [Nephrol Dial Transplant] 2010 Sep; Vol. 25 (9), pp. 3096-106. Date of Electronic Publication: 2010 Mar 17.
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Typ publikacji:
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Journal Article; Multicenter Study; Randomized Controlled Trial
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Język:
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English
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Imprint Name(s):
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Publication: Oxford : Oxford University Press
Original Publication: [Berlin ; New York, NY] : Springer International, [c1986-
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MeSH Terms:
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Graft Survival*
Cyclosporine/*administration & dosage
Graft Rejection/*prevention & control
Immunosuppressive Agents/*administration & dosage
Kidney Failure, Chronic/*therapy
Kidney Transplantation/*mortality
Adolescent ; Adult ; Aged ; Area Under Curve ; Cadaver ; Creatinine/metabolism ; Cyclosporine/pharmacokinetics ; Female ; Follow-Up Studies ; Glomerular Filtration Rate ; Humans ; Immunosuppressive Agents/pharmacokinetics ; Kidney Function Tests ; Male ; Middle Aged ; Mycophenolic Acid/administration & dosage ; Mycophenolic Acid/analogs & derivatives ; Mycophenolic Acid/pharmacokinetics ; Prospective Studies ; Survival Rate ; Tissue Distribution ; Tissue Donors ; Treatment Outcome ; Young Adult
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Substance Nomenclature:
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0 (Immunosuppressive Agents)
83HN0GTJ6D (Cyclosporine)
AYI8EX34EU (Creatinine)
HU9DX48N0T (Mycophenolic Acid)
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Entry Date(s):
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Date Created: 20100320 Date Completed: 20101223 Latest Revision: 20161125
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Update Code:
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20240104
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DOI:
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10.1093/ndt/gfq135
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PMID:
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20299336
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Background: Although cyclosporine maintenance therapy reduces the risk of acute rejection and increases short-term graft survival in renal transplant recipients, its associated nephrotoxicity increases the risk of chronic graft dysfunction. The dose that allows an optimal risk-to-benefit ratio has not been established.
Methods: This multicentre study enrolled stable renal allograft recipients receiving cyclosporine and mycophenolate mofetil without corticosteroids in their second year post-transplant. Patients were randomized to a cyclosporine dose targeted to a standard area under the concentration-time curve (AUC)(0-12 h) (usual exposure, n = 104) or 50% of the study standard AUC(0-12 h) (low exposure, n = 108) using a three-point pharmacokinetic sampling. The primary endpoint was the percentage of patients with treatment failure at 24 months (graft loss/acute rejection/nephrotoxicity/>15% serum creatinine level increase).
Results: Treatment failure was reported in 37 out of 101 (37%) patients in the usual-exposure and 19 out of 106 (18%) patients in the low-exposure groups (P = 0.003). Mean estimated glomerular filtration rate decreased from baseline to 2 years with usual exposure and increased with low exposure (P < 0.001). Mean systolic and diastolic blood pressures were lower with low exposure (P = 0.03 and P = 0.008, respectively).
Conclusion: In renal transplant recipients receiving maintenance therapy without corticosteroids, a minimization strategy using three-point pharmacokinetic sampling to reduce and maintain cyclosporine exposure to 50% of the usual levels is safe and reduces the risk of graft dysfunction.