Two cases of severe de novo colitis in kidney transplant recipients after conversion to prolonged-release tacrolimus

Abstract

Summary Diarrhea is a frequent complication in patients after solid organ transplantation. We describe two cases of severe new onset colitis in kidney transplant recipients that developed shortly after the introduction of the therapy with prolonged‐release formulation of tacrolimus replacing standard twice daily formulation of tacrolimus in one case and cyclosporine A in the second case. Both patients developed severe, intermittent bloody diarrhea with abdominal pain, weight loss, dehydration and worsening graft function that required immediate hospitalization. The symptoms did not diminish after dose reduction or withdrawal of mycophenolic acid derivatives. After excluding bacterial, viral, fungal, and parasite infections, colonoscopy with colonic biopsy was performed in both patients, which revealed features typical of colitis. Both patients received mesalazine until the symptoms stopped. In one of the patients, standard formulation of tacrolimus was immediately reintroduced. The second patient was given everolimus in an acute phase of diarrhea. Although the two cases presented in this report cannot fully support a causal relationship between the prolonged‐release tacrolimus and colitis, they should increase awareness among transplant physicians and prompt more close monitoring of such potential side effects as a part of the pharmacovigilance plan for a new formulation of the well‐established immunosuppressive drug.

Efficacy and Safety of Conversion from Twice-daily to Once-daily Tacrolimus in a Large Cohort of Stable Kidney Transplant Recipients

“…The number of treatment discontinuations was extremely low. No cases of severe new onset colitis (a rare AE recently reported in two renal recipients shortly after the introduction of prolonged‐release tacrolimus (20)) were reported.…”

Secondary causes of inflammatory bowel diseases

“…The use of tacrolimus has been reported to induce a flare of pre-existing IBD among individuals with solid organ trans-plantation[ 29 ]. Its use has also been shown to be associated with the development of de novo IBD[ 29 , 30 ]. In an observational study of 53 patients without a diagnosis of IBD who underwent liver transplantation, 6 (11%) of them developed de novo IBD during a median follow up of 3.9 years[ 29 ].…”

Conventional Medical Management of Ulcerative Colitis: Tacrolimus

“…A greater concern is the publication of a series of studies suggesting that tacrolimus could be attributed to the de novo development of ulcerative colitis in liver transplant recipients [ 53,54 ] or Crohn's disease in solid organ transplant recipients [55][56][57][58] . The underlying hypothesis that calcineurin induced reduction of T reg or TGF-b expression predisposes non-transplanted tissue to inflammation, is challenged by another study [ 59 ] .…”