MMF Rocks!!

Am J Transplant. 2007 Feb;7(2):366-76.

Mycophenolate mofetil is associated with altered expression of chronic renal transplant histology.

* Nankivell BJ,
* Wavamunno MD,
* Borrows RJ,
* Vitalone M,
* Fung CL,
* Allen RD,
* Chapman JR,
* O'Connell PJ.

Department of Renal Medicine, University of Sydney, Westmead Hospital, Westmead 2145, Sydney, NSW, Australia. Brian_Nankivell@wsahs.nsw.gov.au

Mycophenolate mofetil (MMF) reduces acute rejection in controlled trials of kidney transplantation and is associated with better registry graft survival. Recent experimental studies have demonstrated additional antifibrotic properties of MMF, however, human histological data are lacking.

We evaluated sequential prospective protocol kidney biopsies from two historical cohorts treated with cyclosporine (CSA)-based triple therapy including prednisolone and either MMF (n = 25) or azathioprine (AZA, n = 25). Biopsies (n = 360) were taken from euglycemic kidney-pancreas transplant recipients. Histology was independently assessed by the Banff schema and electron microscopic morphometry.

MMF reduced
acute rejection and OKT3 use (p < 0.05) compared with AZA.
MMF therapy was associated with
limited chronic interstitial fibrosis,
striped fibrosis and periglomerular fibrosis (p < 0.05-0.001),
mesangial matrix accumulation (p < 0.01),
chronic glomerulopathy scores (p < 0.05)
glomerulosclerosis (p < 0.05).
MMF was associated with
delayed expression of CSA nephrotoxicity,
reduced arteriolar hyalinosis,
striped fibrosis and
tubular microcalcification (p < 0.05-0.001).
The beneficial effects of MMF remained in recipients without acute rejection.

MMF therapy was associated with
substantially reduced fibrosis in the glomerular,
microvascular and interstitial compartments,
delayed expression of CSA nephrotoxicity.

These outcomes may be due to a limitation of immune-mediated injury and suggest a direct effect of reduced fibrogenesis.