title: Incidence of posttransplant diabetes mellitus in kidney transplant recipients immunosuppressed with sirolimus in combination with cyclosporine.
abstract: Sirolimus (SRL) in combination with Cyclosporine A (CsA) and steroids has been shown to lower the incidence of acute renal allograft rejection episodes, allowing CsA sparing. We retrospectively compared the incidence of posttransplant diabetes mellitus (PTDM) among kidney transplant recipients (KTx) immunosuppressed with SRL + CsA versus CsA alone. Patients were divided into two groups: SRL + CsA (n = 38) versus CsA (n = 48). Mean follow-up was 53.9 +/- 17.1 months. Seventeen/86 subjects (19.8%) developed diabetes after transplantation (7 IFG, 8.1%; 10 PTDM, 11.6%). The incidence was significantly higher in SRL + CsA (12/38 patients, 31.6%) compared with CsA (5/43 patients, 10.4%) (P = .0144, odds ratio 3.97). More patients required treatment in the SRL + CsA compared to CsA alone cohort (13.2% vs 2.1%, P = .051): 4 pts (10.5%) became insulin- dependent among SRL+CsA, vs none in the CsA group. Use of OHD was similar in both groups (2.6% SRL + CsA vs 2.1% CsA). There were no significant differences between the two groups in terms of age, sex distribution, BMI, or serum creatinine at 1 to 3 and 5 years from transplantation. All PTDM patients are alive at follow-up, while two grafts were lost due to chronic renal allograft dysfunction. Within the limits of a small retrospective study, we observed that SRL in combination with CsA increased the diabetogenic potential of CsA. A possible explanation of our findings is that higher CsA doses were used in the early experience with SRL + CsA; therefore the higher incidence of PTDM that we observed in the SRL + CsA combination may be a sign of toxicity. Careful monitoring of blood levels is mandatory in the SRL + CsA combination to avoid pleiotropic toxicity.
authors.affiliation: Department of Surgery, Organ Transplantation, Catholic University, Policlinico Gemelli, Rome, Italy. jromagnoli@rm.unicatt.it
authors.forename: J
authors.initials: J
authors.lastname: Romagnoli
authors.forename: F
authors.initials: F
authors.lastname: Citterio
authors.forename: G
authors.initials: G
authors.lastname: Nanni
authors.forename: E
authors.initials: E
authors.lastname: Favi
authors.forename: V
authors.initials: V
authors.lastname: Tondolo
authors.forename: G
authors.initials: G
authors.lastname: Spagnoletti
authors.forename: M Paola
authors.initials: MP
authors.lastname: Salerno
authors.forename: M
authors.initials: M
authors.lastname: Castagneto
mesh_terms: D000328:Adult; D016572:Cyclosporine / Q000009:adverse effects*; D003920:Diabetes Mellitus / Q000453:epidemiology*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D015994:Incidence; D007328:Insulin / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000453:epidemiology; D012189:Retrospective Studies; D020123:Sirolimus / Q000009:adverse effects*
chemical_list: D007004:Hypoglycemic Agents; D007166:Immunosuppressive Agents; D007328:Insulin; D016572:Cyclosporine; D020123:Sirolimus