Paul Bolin Jr, MD, PhD, of the Brody School of Medicine at East Carolina University, and colleagues report that switching from mycophenolate mofetil (MMF) to enteric mycophenolate sodium (EC-MPS) in renal transplant patients with comorbid diabetes increases mycophenolic acid (MPA) exposure but reduces gastrointestinal symptoms, allowing patients to tolerate maintenance therapy. This review was published in the July issue of Transplantation Reviews (Transplantation Reviews 2011. doi:10.1016). On the one hand, diabetic nephropathy has become the most common indication for kidney transplantation (about 1/3 in the United States) and continues to increase, and on the other hand, about 20% of kidney transplant patients have new onset of diabetes after surgery due to continued immunosuppressive therapy, and about 1/3 of kidney transplant patients have impaired fasting glucose. The survival rate of renal transplant patients with combined diabetes is 5% to 20% lower than that of patients without combined diabetes at 3 to 5 years after surgery. In addition, these patients often suffer from gastrointestinal complications such as dysphagia, reflux, constipation, bloating, anorexia, and diarrhea. 30% to 50% of patients with type 1 or type 2 diabetes have delayed gastric emptying, which adversely affects the absorption of oral medications. Renal transplant patients with combined diabetes mellitus are at a much higher risk of GI toxicity due to prolonged retention of the drug in the stomach. The efficacy of enteral mycophenolate sodium in renal transplant patients is comparable to that of mycophenolate, and a major randomized trial comparing enteral mycophenolate sodium with mycophenolate did not observe a difference in efficacy endpoints. An open study that included 456 renal transplant patients taking enteral mycophenolate sodium showed that 17.7% of the subgroup of patients with pre-transplant diabetes had biopsy-proven acute rejection at 12 months post-operatively, a lower percentage than in non-diabetic patients (23.1%, a non-significant difference). More importantly, enteric mycophenolate sodium releases mycophenolic acid only at pH above 5.5, which is absorbed more distally in the GI tract compared to mycophenolate esters and may theoretically mitigate GI toxicity. An open multicenter study showed that switching from mycophenolate to enteral sodium mycophenolate in renal transplant patients with GI complications reduced GI symptom load. Several studies have shown that patients who were forced to reduce their mycophenolate dose because they could not tolerate GI symptoms tolerated larger doses of mycophenolate after switching to enteric-soluble mycophenolate sodium. And large registry studies and retrospective analyses have shown that maintaining the recommended dose of mycophenolic acid implies increased survival of renal grafts. Renal transplant patients who already have diabetes-related GI complications are likely to be more sensitive to the GI toxicity of mycophenolic acid, so there may be greater benefit in switching from mycophenolate to enterolysis mycophenolate sodium. A recent study, myGAIN, evaluated the effect of switching from mycophenolate to enteral mycophenolate sodium on GI symptom load. This prospective, double-blind, multicenter study enrolled 396 maintenance renal transplant patients who were experiencing GI symptoms as a result of mycophenolate. Subjects were randomized to switch to enteric mycophenolate sodium or to continue taking mycophenolate esters. Results showed that among the 146 patients with combined diabetes, more patients in the group switched to enteral mycophenolate sodium had a ≥0.3-point improvement in 4-week Gastrointestinal Symptom Rating Scale (GSRS) scores from baseline (69.6% vs 44.7%, P=0.009). At this point, mycophenolic acid trough concentrations were higher in those with comorbid diabetes than in those without diabetes (3.8 ng/ml vs. 3.4 ng/ml) in patients who switched to enteral mycophenolate sodium, and vice versa in those who continued mycophenolate esters (2.9 ng/ml vs. 3.4 ng/ml), thus suggesting greater systemic exposure to mycophenolic acid with enteral mycophenolate sodium and supporting “mycophenolic acid toxicity is primarily determined by local exposure” and suggests that switching to enteric mycophenolate sodium may increase the amount of mycophenolic acid tolerated by patients.