Mr Magdi Shehata
Consultant Surgeon, Nottingham City
Hospital
Gastro-intestinal
(GI) side-effects, in particular diarrhoea is a frequently reported problem in
clinical trials. It occurs with all
immunosuppressive drugs, with greater frequency in patients receiving
Mycophenolate Mofetil (MMF) especially when combined with Tacrolimus (FK). Immunosuppression-induced diarrhoea may be
caused by disorders in gut motility, inflammatory mediators or abnormalities in
cell function. In kidney transplant
recipients, pre-existing diseases such as diabetes, CMV infection, antibiotics
and a plethora of medications could also cause diarrhoea.
Tacrolimus, sirolimus and everolimus are known to have stimulatory
effect on gastric and duodenal motility, while MMF increases colonic
transit. The latter appear to be
inversely related to mycophenolic acid (MPA) levels. Patients with diarrhoea may also have a degree of malabsorption
(enteropathy). This may involve fat,
bile salts or lactose absorption. In
turn this may cause diarrhoea via colonic irritation or osmotic activity.
Assessment
of diarrhoea in transplant recipients is difficult as it is based on
self-reporting and the lack of strict definition of diarrhoea. Initial investigation should rule out gut
infection (bacterial, viral etc) by culture, PCR and endoscopy. Bacterial overgrowth secondary to over
immunosuppression is difficult to diagnose.
Antimotility drug may be beneficial in some cases. If no cause found
then attention should be directed to immunosuppressive drugs and dose reduction
or a change of therapy may be considered.