ABCB1 genotypes predict cyclosporine-related adverse events and kidney allograft outcome

Dario Cattaneo, Piero Ruggenenti, Sara Baldelli, Nicola Motterlini, Eliana Gotti, Silvio Sandrini, Maurizio Salvadori, Giuseppe Segoloni, Paolo Rigotti, Donato Donati, Norberto Perico, Giuseppe Remuzzi

Research output: Contribution to journalArticlepeer-review

Abstract

Cyclosporine A (CsA) is a substrate of P-glycoprotein, an efflux transporter encoded by the ABCB1 gene. Compared with carriers of the wild-type gene, carriers of T allelic variants in exons 21 or 26 have reduced P-glycoprotein activity and, secondarily, increased intracellular concentration of CsA; therefore, carriers of T variants might be at increased risk for CsA-related adverse events. We evaluated the associations between ABCB1 genotypes (in exons 12, 21, and 26) and CsA-related outcomes in 147 renal transplant recipients who were receiving CsA-based immunosuppression and were included in the Mycophenolate Steroids Sparing study. During a median of 65.5 mo follow-up, carriers of T allelic variants in exons 21 or 26 had a three-fold risk for delayed graft function (DGF), a trend to slower recovery of renal function and lower GFR at study end, and significantly higher incidences of new-onset diabetes and cytomegalovirus reactivation compared with carriers of the wild-type genotype. T variants in both exons 21 and 26 were independently associated with 3.8- and 3.5-fold higher risk for DGF, respectively (P = 0.022 and P = 0.034). The incidence of acute rejection and the mean CsA dose and blood levels were comparable in genotype groups. In conclusion, renal transplant recipients with T allelic variants in ABCB1 exons 21 or 26 are at increased risk for CsA-related adverse events. Genetic evaluation may help to identify patients at risk and to modulate CsA therapy to optimize graft and patient outcomes.

Original languageEnglish
Pages (from-to)1404-1415
Number of pages12
JournalJournal of the American Society of Nephrology
Volume20
Issue number6
DOIs
Publication statusPublished - Jun 2009

ASJC Scopus subject areas

  • Nephrology

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