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A Journal on Nephrology and Urology

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Minerva Urologica e Nefrologica 2003 March;55(1):33-42

language: English

Metabolic aspects of tacrolimus in renal trans-plantation. Consequences for the choice of an immunosuppressive regimen and for the management of post-transplant diabetes mellitus

Van Duijnhoven E. M., Boots J. M. M., Christiaans M. H. L., Van Hooff J. P.

Depart­ment of Inter­nal Med­i­cine, Uni­ver­sity Hos­pi­tal Maas­tricht, Maas­tricht, The Neth­er­lands

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The occur­rence of ­post-trans­plan­t dia­betes mel­lit­us (­PTDM) is an impor­tant com­pli­ca­tion ­after ­renal trans­plan­ta­tion asso­ciat­ed ­with an ­increased ­risk of chron­ic trans­plant dys­func­tion and of car­di­o­vas­cu­lar mor­bid­ity and mor­tal­ity. ­Both tacrol­i­mus and cyclo­spo­rine ­have ­been asso­ciat­ed ­with ­PTDM. In the ­initial stud­ies, ­PTDM ­seemed to ­occur ­more ­often in tacrol­i­mus treat­ed ­patients ­than in cyclo­spo­rine treat­ed ­patients. The mech­a­nism by ­which tacrol­i­mus ­could ­cause ­PTDM was ­unknown and the rel­a­tive ­roles of tacrol­i­mus and cor­ti­cos­ter­oids, ­which are ­often pre­scribed con­com­i­tant­ly ­with tacrol­i­mus, ­were ­unknown. In sev­er­al stud­ies we ­used fast­ing glu­cose and insu­lin lev­els to ­assess (periph­er­al) insu­lin resis­tance, and intra­ve­nous glu­cose tol­er­ance ­tests to ­assess insu­lin secre­tion by the pan­creat­ic β-­cells in ­response to a stim­u­lus (glu­cose ­load). ­Thus, we eval­u­at­ed the mech­a­nism by ­which tacrol­i­mus caus­es glu­cose meta­bol­ic dis­or­ders, ­risk fac­tors for glu­cose meta­bol­ic dis­or­ders dur­ing tacrol­i­mus treat­ment, the rel­a­tive ­roles of cor­ti­cos­ter­oids and tacrol­i­mus ­trough lev­els in glu­cose meta­bol­ic dis­or­ders, and ­also dif­fer­enc­es in glu­cose metab­olism ­between ­patients ­using tacrol­i­mus ver­sus ­patients ­using cyclo­spo­rine. ­Based on the ­results of ­these stud­ies and the avail­able lit­er­a­ture, the con­se­quenc­es for the ­choice of a pri­mary immu­no­sup­pres­sive ­agent and guide­lines for the treat­ment of ­PTDM dur­ing tacrol­i­mus-­based immu­no­sup­pres­sion are dis­cussed.

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