Fecal beta-glucuronidase activity differs between hematopoietic cell and kidney transplantation and a possible mechanism for disparate dose requirements

The intestinal microbiota produces beta-glucuronidase that plays an essential role in the metabolism of the immunosuppressant mycophenolate mofetil (MMF). This drug is commonly used in organ and hematopoietic cell transplantation (HCT), with variations in dosing across transplant types. We hypothesized that beta-glucuronidase activity differs between transplant types, which may account for differences in dosing requirements. We evaluated fecal beta-glucuronidase activity in patients receiving MMF post-allogeneic HCT and post-kidney transplant. Kidney transplant patients had significantly greater beta-glucuronidase activity (8.48 +/- 6.21 nmol/hr/g) than HCT patients (3.50 +/- 3.29 nmol/hr/g; P = .001). Microbially mediated beta-glucuronidase activity may be a critical determinant in the amount of mycophenolate entering the systemic circulation and an important factor to consider for precision dosing of MMF.