Conversion from calcineurin inhibitors to mycophenolate mofetil in liver transplant recipients with diabetes mellitus

Abstract

Diabetes mellitus, a frequent metabolic complication in liver transplant recipients, may be produced by the diabetogenic effect of calcineurin inhibitors cyclosporine and tacrolimus. The aim of this study was to investigate the safety and metabolic effects of a gradual switch from cyclosporine or tacrolimus to mycophenolate mofetil among 12 diabetic liver transplant recipients. One patient was withdrawn from the study due to gastrointestinal side effects. Of the 11 remaining patients, cyclosporine or tacrolimus was completely withdrawn in five patients. Two patients developed suspected acute rejection episodes that were controlled by increasing the tacrolimus dosage. Glycosylated hemoglobin A1C and C-peptide levels were significantly lower at 3 and 6 months after the initiation of mycophenolate mofetil (P < .03 in all cases). Furthermore, urea and uric acid levels were significantly reduced after the change of treatment. In conclusion, a switch from cyclosporine/tacrolimus to mycophenolate mofetil may produce beneficial metabolic effects in diabetic liver transplant recipients, but poses a risk of graft rejection. I D ABETES MELLITUS (DM) is a frequent metabolic complication in liver transplant(LT) recipients. Despite the lack of universal agreement, some studies have observed worsened short-and mid-term survival among diabetic LT recipients. 1-7 Furthermore, DM is a wellknown risk factor for cardiovascular disease, which is one of the leading causes of death of LT recipients in the long term. 8 Calcineurin inhibitors (CI) also predispose to DM through islet cell toxicity, diminished insulin synthesis or release, as well as decreased peripheral insulin sensitivity. 9 Mycophenolate mofetil (MMF) has proven to be useful as a CI-sparing agent. The use of MMF has allowed physicians to reduce cyclosporine exposure in LT recipients with renal functional impairment. 10 Some patients have been maintained on MMF monotherapy, but this strategy poses the risk of graft rejection. 11 The aim of the present study was to examine whether conversion to MMF for stable LT recipients with DM allows the reduction/withdrawal of CI and results in improve metabolic control.From the Liver Unit (J.I.H., J.Q., B.S., J.P.) and

Free Fatty Acids Are Associated with Obesity, Insulin Resistance, and Atherosclerosis in Renal Transplant Recipients

“…There is substantial evidence in the literature that both calcineurin inhibitors (particularly tacrolimus) and steroids significantly increase the risk of developing IR and posttransplant diabetes mellitus (16,17,36,37). In this study, only corticosteroids were found to be predictive of IR.…”

Calcineurin inhibitor‐sparing regimens in solid organ transplantation: focus on improving renal function and nephrotoxicity

“…When CNI withdrawal was compared with CNI minimization with mycophenolate mofetil introduction, 62.5% vs. 50–60% had normalization of SCr, respectively (85). Use of mycophenolate mofetil to withdraw CNI was associated with improvement in SCr in 77–100% of patients and an increase in CrCl of about 9–11 mL/min (86–92). Expectedly, a study of diabetic patients with normal renal function demonstrated no improvement in SCr at six months (92).…”

“…Use of mycophenolate mofetil to withdraw CNI was associated with improvement in SCr in 77–100% of patients and an increase in CrCl of about 9–11 mL/min (86–92). Expectedly, a study of diabetic patients with normal renal function demonstrated no improvement in SCr at six months (92). Complete CNI withdrawal was achieved in 45–100% of patients, leading to better renal function than those maintained on low‐dose CNI (Fig.…”

“…Complete CNI withdrawal was achieved in 45–100% of patients, leading to better renal function than those maintained on low‐dose CNI (Fig. 1) (86–89, 91, 92). Conversion to mycophenolate mofetil appeared to be more effective when the preceding duration of SCr elevation was less than six months (100%) compared with greater than one yr (77%) (86).…”

New-onset diabetes after liver transplantation: From pathogenesis to management

“…However, reduction of tacrolimus dose in liver transplant patients in whom NODM develops may be of only limited benefit, and switching from tacrolimus to cyclosporine may be appropriate 51, 52. A further option may be switching patients with NODM to a calcineurin inhibitor–free regimen; preliminary evidence from a study of 12 liver transplant patients, of whom 5 were successfully converted to mycophenolate mofetil, suggests that this may be a feasible strategy to significantly improve glycemic control 53. However, selection of immunosuppression regimen in high‐risk patients to minimize risk of NODM developing should never jeopardize graft survival.…”