Immunosuppressive therapy and infection after kidney transplantation.

J.Fortun,P.Martin-Davila,J.Pascual,C.Cervera,A.Moreno,J.Gavalda,J.M.Aguado,P.Pereira,M.Gurgu|¤,J.Carratala,M.Fogueda,M. Montejo, F. Blasco, G. Bou, J.Torre-Cisneros; RESITRATransplantNetwork. Immunosuppressive therapy and infection afterkidneytransplantation.TransplInfectDis2010:12:397^405.AllrightsreservedAbstract: Background.The role of immunosuppressive drugs inthedevelopmentof infection intransplant recipients hasbeen poorlyanalyzed.Objective.To evaluate the possible associationbetween infection andimmunosuppressionregimensinalarge cohortof renaltransplantrecipients.Methods. AllrenaltransplantrecipientsincludedintheRESITRAprospectivecohort from August2003toFebruary2005withaminimum follow-up of 3 monthswere studied. An intention-to-treatanalysiswas performed and patientswere analyzed in groupsaccording tothetype ofinductionandinitialmaintenancetherapy.V|ral,bacterial,andfungalinfectionsoccurringduring thisperiodwere evaluated.Results. Atotalof1398renaltransplant recipientswerestudied.Amaintenance regimen containing sirolimuswas independentlyassociatedwithalower riskofcytomegalovirus(CMV)infection(oddsratio [OR],0.16; 95%con¢dence interval [CI],0.05^0.54) andwith ahigher rate of surgical site infection (OR,3.21; 95%CI,1.26^8.21).Excludingtreatmentusedforacuterejectionepisodes,nootherfactorsrelatedtotheimmunosuppression regimenswereassociatedwiththedevelopmentofbacteremia,urinaryinfections,pneumonia,orotherinfections.Conclusion.The use of sirolimus as maintenance therapy in kidneyrecipientsisassociatedwithalow rate ofCMVinfectionandwithahigher riskofsurgicalsite infection.2009, accepted for publication 22 December 2009Correspondence to:Madrid, SpainIn recentyears,ashifthasbeenobservedtowardtheroutineuse of induction therapy with antibody preparations andmaintenancetherapywithamammaliantargetofrapamycin(mTOR) inhibitor (sirolimus or everolimus) to avoid the ne-phrotoxicityassociatedwithcalcineurin inhibitors(1).Calcineurin inhibitors are still the main cause ofimmunosuppression in the maintenance regimens takenby kidney recipients.Tacrolimus is the agent of choice andisincreasingly used:470%ofpatients are receiving tacro-limus at discharge compared with 20% who receive cyclo-sporine (1).The use of mycophenolate mofetil (MMF), themost frequently prescribed antiproliferative agent, is alsoincreasing: approximately 80% of patients are taking thisdrug at discharge (1). Calcineurin inhibitor-sparing regi-mensincludingsirolimusandMMFcombinedwithcortico-steroids have been proposed as a less nephrotoxicalternative. However, the results obtained with thiscombination have been questioned (2), and the potentiale⁄cacyof sirolimus as the main immunosuppressive druginthe combination needsto bebalanced against its safetypro¢le.Major progress has been made in the development andclinical application of novel immunosuppressive drugs toprevent acute rejection. However, few protocols includemonitoring of infectious diseases (3). Althoughthe associ-ation between immunosuppressive drugs and infection iswell known, the speci¢c contribution of diierent drugs totheseinfectionshasbeenpoorlyanalyzed.