Incidence of Posttransplantation Diabetes Mellitus in De Novo Kidney Transplant Recipients Receiving Prolonged-Release Tacrolimus-Based Immunosuppression With 2 Different Corticosteroid Minimization Strategies

Abstract

BackgroundADVANCE (NCT01304836) was a phase 4, multicenter, prospectively randomized, open-label, 24-week study comparing the incidence of posttransplantation diabetes mellitus (PTDM) with 2 prolonged-release tacrolimus corticosteroid minimization regimens.MethodsAll patients received prolonged-release tacrolimus, basiliximab, mycophenolate mofetil and 1 bolus of intraoperative corticosteroids (0-1000 mg) as per center policy. Patients in arm 1 received tapered corticosteroids, stopped after day 10, whereas patients in arm 2 received no steroids after the intraoperative bolus. The primary efficacy variable was the diagnosis of PTDM as per American Diabetes Association criteria (2010) at any point up to 24 weeks postkidney transplantation. Secondary efficacy variables included incidence of composite efficacy failure (graft loss, biopsy-proven acute rejection or severe graft dysfunction: estimated glomerular filtration rate (Modification of Diet in Renal Disease-4) <30 mL/min per 1.73 m2), acute rejection and graft and patient survival.ResultsThe full-analysis set included 1081 patients (arm 1: n = 528, arm 2: n = 553). Baseline characteristics and mean tacrolimus trough levels were comparable between arms. Week 24 Kaplan–Meier estimates of PTDM were similar for arm 1 versus arm 2 (17.4% vs 16.6%; P = 0.579). Incidence of composite efficacy failure, graft and patient survival, and mean estimated glomerular filtration rate were also comparable between arms. Biopsy-proven acute rejection and acute rejection were significantly higher in arm 2 versus arm 1 (13.6% vs 8.7%, P = 0.006 and 25.9% vs 18.2%, P = 0.001, respectively). Tolerability profiles were comparable between arms.ConclusionsA prolonged-release tacrolimus, basiliximab, and mycophenolate mofetil immunosuppressive regimen is efficacious, with a low incidence of PTDM and a manageable tolerability profile over 24 weeks of treatment. A lower incidence of biopsy-proven acute rejection was seen in patients receiving corticosteroids tapered over 10 days plus an intraoperative corticosteroid bolus versus those receiving an intraoperative bolus only.

Randomized Controlled Trial Assessing the Impact of Tacrolimus Versus Cyclosporine on the Incidence of Posttransplant Diabetes Mellitus

“…Compared with SM, rapid SW in tacrolimus-treated patients did not provide a further reduction of PTDM. The associated slight increase in BPAR (11.4% vs. 4.8%), a specific risk factor of PTDM due to the concomitant use of high corticosteroid doses, 1 , 2 , 3 , 40 may at least partly explain this finding. In fact, 3 of the 5 patients with BPAR developed PTDM.…”

“…The observed 26% incidence compares favorably with the reported 44% to 56% in high-risk patients, 15 , 16 and falls within the 17% to 39% observed in the transplant population at large. 16 , 22 , 40 Additionally, PTDM was manageable because only 1 patient required insulin therapy at study end and the mean HbA1c was <7% (6.4 ± 0.6; 95% confidence interval 5.7%–7.0%). Finally, the consistent improvement in glucose metabolism from 3 to 12 months due to decreasing immunosuppression ( Figure 4 ) underscores the partial reversibility of tacrolimus-induced dysglycemia.…”

Steroid-induced hyperglycemia: An underdiagnosed problem or clinical inertia? A narrative review

“…Therefore, glucose monitoring across the first 48 hours is very important in order to identify the most patients developing hyperglycemia, stopping further testing in case of absence of hyperglycemia within the first 48 hours [37]. Table 2 summarizes epidemiological data divided by different conditions according to main recent studies published within 2015 and 2018 [29,[38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54].…”

Perioperative Care for Kidney Transplant Recipients

“…The post-operative stress response, combined with induction corticosteroid and cyclosporine or tacrolimus therapy, can result in significant perioperative hyperglycaemia even in patients who do not have pre-existing diabetes, with a reported incidence as high as 80-90% in some studies [67,68] with post-transplant diabetes persisting in 10-45% depending on the definition used [69][70][71][72][73]. Hyperglycaemia is also associated with rejection in the perioperative period and in the long term carries adverse metabolic outcomes [74].…”