How Delayed Graft Function Impacts Exposure to Mycophenolic Acid in Patients After Renal Transplantation

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dc.contributor.authorvan Gelder, Teun
dc.contributor.authorSilva, Helio Tedesco [UNIFESP]
dc.contributor.authorFijter, Hans de
dc.contributor.authorBudde, Klemens
dc.contributor.authorKuypers, Dirk
dc.contributor.authorMamelok, Richard D.
dc.contributor.authorArmstrong, Victor W.
dc.contributor.authorOellerich, Michael
dc.contributor.institutionErasmus MC
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionLeiden Univ
dc.contributor.institutionCharite
dc.contributor.institutionLeuven Univ
dc.contributor.institutionMamelok Consulting
dc.contributor.institutionUniv Gottingen
dc.date.accessioned2016-01-24T14:06:23Z
dc.date.available2016-01-24T14:06:23Z
dc.date.issued2011-04-01
dc.description.abstractIntroduction: Mycophenolic acid (MPA) plasma concentrations are highly variable on standard-dose mycophenolate mofetil therapy. At creatinine clearances below 25 mL/min, MPA clearance increases as a result of a higher nonprotein-bound fraction. Patients with delayed graft function (DGF) after renal transplantation are exposed to low total MPA concentrations, when risk of rejection is highest. This study investigated the influence of DGF on MPA exposure and on clinical outcome.Methods: Adult renal transplantation patients treated with mycophenolate mofetil, corticosteroids, and either microemulsified cyclosporine (n = 459) or tacrolimus (n = 371) participated in a randomized controlled trial (the Fixed-Dose Concentration-Controlled [FDCC] Study). Abbreviated MPA areas under the curve (AUCs) were obtained on Day 3, Day 10, Week 4, and Month 3, to calculate MPA AUC((0-12)). Free MPA AUC values were available for a subgroup of patients (n = 269).Results: the overall incidence of DGF was 187 of 830 (23%) and did not differ between cyclosporine-treated (24%) and tacrolimus-(21%) treated patients. the incidence of biopsy-proven acute rejection at 12 months was significantly higher in patients with DGF (13.8% versus 21.4%). Patients with DGF had significantly lower dose-corrected MPA AUC on Day 3 and Day 10. Free MPA fraction and dose-corrected free MPA AUC were significantly higher in patients with DGF, from Day 3 until Month 3. the total number of patients with at least one opportunistic infection was significantly higher in patients with DGF (33.2%) compared with patients without DGF (25.8%) (P = 0.048). Patients with DGF developing opportunistic infections did not have higher total MPA AUC nor higher free MPA AUC compared with those without opportunistic infections.Conclusion: Patients with DGF have significantly lower dose-corrected MPA AUC in the first month after renal transplantation, presumably as a result of enhanced MPA clearance on account of the elevated MPA free fraction. Because patients with DGF have a higher rate of acute rejection and lower MPA exposure, higher dosing of mycophenolate mofetil in such patients may improve outcome. However, the already increased incidence of opportunistic infections in patients with DGF is a concern.en
dc.description.affiliationErasmus MC, Dept Hosp Pharm, Clin Pharmacol Unit, NL-3000 CA Rotterdam, Netherlands
dc.description.affiliationErasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands
dc.description.affiliationUniversidade Federal de São Paulo, Hosp Rim & Hipertensao, Dept Nephrol, São Paulo, Brazil
dc.description.affiliationLeiden Univ, Med Ctr, Dept Nephrol, Leiden, Netherlands
dc.description.affiliationCharite, Dept Nephrol, D-13353 Berlin, Germany
dc.description.affiliationLeuven Univ, Dept Nephrol & Renal Transplantat, Louvain, Belgium
dc.description.affiliationMamelok Consulting, Palo Alto, CA USA
dc.description.affiliationUniv Gottingen, Klin Chem Abt, D-3400 Gottingen, Germany
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Hosp Rim & Hipertensao, Dept Nephrol, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipF. Hoffmann-La Roche Ltd, Basel, Switzerland
dc.format.extent155-164
dc.identifierhttp://dx.doi.org/10.1097/FTD.0b013e31820c0a96
dc.identifier.citationTherapeutic Drug Monitoring. Philadelphia: Lippincott Williams & Wilkins, v. 33, n. 2, p. 155-164, 2011.
dc.identifier.doi10.1097/FTD.0b013e31820c0a96
dc.identifier.issn0163-4356
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/33615
dc.identifier.wosWOS:000288498100004
dc.language.isoeng
dc.publisherLippincott Williams & Wilkins
dc.relation.ispartofTherapeutic Drug Monitoring
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectmycophenolate mofetilen
dc.subjecttransplantationen
dc.subjecttherapeutic drug monitoringen
dc.titleHow Delayed Graft Function Impacts Exposure to Mycophenolic Acid in Patients After Renal Transplantationen
dc.typeinfo:eu-repo/semantics/article
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