Objectives: Mycophenolate mofetil (MMF) causes gastrointestinal adverse effects in 45% of kidney transplant recipients, as enterocytes are partially dependent on the de-novo pathway of purine synthesis. The study aims to describe the outcomes of immunosuppression modification in symptomatic kidney transplant recipients having histopathological evidence of MMF-related toxicity.
Methods: A retrospective observational study from January 2009 to December 2018 at a tertiary care center in north India. All cases that had evidence of MMF-associated histopathological changes and underwent immunosuppression modification were included and studied.
Results: Among 122 recipients who underwent endoscopic biopsy, MMF-associated histopathological changes were observed in 102 (83.6%) cases. The indication of endoscopy was persistent or chronic diarrhea in 83.3% (n=85) and non-diarrheal causes in 16.7% (n=17) cases. The associated features were anemia (45.1%, n=46), weight loss (37.3%, n=38), and rectal bleeding (6.9%, n=7). The median duration was 57 (IQR 17-74) months post-transplant. The mean creatinine was 1.84 ± 0.91 mg/dl at the time of biopsy. All patients were on a triple immunosuppressive regimen, with either mycophenolate mofetil (81.4%, n=83) or enteric-coated mycophenolate sodium (16.7%, n=17). The comorbidities included diabetes (40.2%, n=41), tuberculosis (26.5%, n=27), CMV infection (37.3%, n=38), prior antirejection therapy (33.3%, n=34), and chronic renal allograft injury (46.1%, n=47). 2 cases had coexisting post-transplant lymphoproliferative disorder.
Despite conservative management and treatment of associated conditions, 61 (59.8%) patients with persistent symptoms required immunosuppressive drug modification. MMF was changed to enteric-coated mycophenolate sodium (ECMPS) in 20 cases, Azathioprine in 25 cases, and mTOR inhibitors in 4 cases, while MMF/ECMPS was discontinued completely in 12 cases. A significant number of patients (n=18, 29.5%) developed biopsy-proven rejection after drug modification (p=0.002). However, the difference in graft loss after immunosuppression modification was not significant (p=0.24). MMF was reintroduced in 6 patients, but two patients had diarrhea recurrence. During a median follow-up period of 30 months in the immunosuppression modification group, ten patients had chronic renal allograft injury (CRAI), including five graft losses; 17 patients died, and 19 patients were lost to follow-up.


Conclusions: GI toxicity related to mycophenolate therapy is pretty prevalent in kidney transplant recipients. The severe symptomatic cases require immunosuppression modification, which can result in an increased risk of rejection and de-novo DSA formation.