title: Calcineurin inhibitor dose-finding before kidney transplantation in HIV patients.
abstract: Kidney transplantation in HIV-infected patients is associated with a higher rate of graft rejection as well as an increased toxicity of the immunosuppressive therapy. Specifically, the use of the calcineurin inhibitor tacrolimus is problematic because of a narrow therapeutic range, a high interindividual variability of trough levels, and multiple interactions with combination antiretroviral therapy (cART). Our objective was to establish the optimal individual immunosuppressive dose for the time after kidney transplantation. We administered a temporary course of immunosuppressive therapy in three HIV-infected patients with end-stage renal disease (ESRD) after wait-listing and prior to transplantation for deceased donor kidney transplantation. Starting with a tacrolimus dose of 1 mg twice daily, the dose was titrated to reach a tacrolimus trough level of 8-12 ng/ml. HIV had been diagnosed 7-14 years prior. All patients had no detectable HIV-1 RNA while on cART. All three patients had been on chronic dialysis for 4, 7, and 10 years. In two patients, the intended tacrolimus trough levels of 8-12 ng/ml were achieved within a month. The required tacrolimus dose ranged from 0.5 mg thrice weekly to 10 mg daily. In one case, ventricular tachycardia occurred, so the immunosuppressive therapy was switched to cyclosporine A. So far, two patients have been transplanted successfully. In summary, dose-finding of immunosuppressive therapy with tacrolimus in patients on cART before renal transplantation is feasible and appears useful to minimize immunosuppressive therapy-related complications in the post-transplantation period.
authors.affiliation: Division of Nephrology, Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Alina
authors.initials: A
authors.lastname: Pulzer
authors.forename: Ulrich
authors.initials: U
authors.lastname: Seybold
authors.forename: Ulf
authors.initials: U
authors.lastname: Schönermarck
authors.forename: Manfred
authors.initials: M
authors.lastname: Stangl
authors.forename: Antje
authors.initials: A
authors.lastname: Habicht
authors.forename: Johannes R
authors.initials: JR
authors.lastname: Bogner
authors.forename: Jörg
authors.initials: J
authors.lastname: Franke
authors.forename: Michael
authors.initials: M
authors.lastname: Fischereder
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage; D065095:Calcineurin Inhibitors; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006085:Graft Survival; D015658:HIV Infections / Q000175:diagnosis* / Q000188:drug therapy / Q000601:surgery; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007676:Kidney Failure, Chronic / Q000175:diagnosis / Q000276:immunology / Q000601:surgery*; D016030:Kidney Transplantation / Q000276:immunology / Q000379:methods*; D008297:Male; D008875:Middle Aged; D061214:Patient Safety; D011300:Preoperative Care / Q000379:methods; D018570:Risk Assessment; D012494:Sampling Studies; D016559:Tacrolimus / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D044966:Anti-Retroviral Agents; D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016559:Tacrolimus