CSI Clinical Science Investigations: Where Science Meets the Bedside

12:35 Pathogenesis and treatment of chronic antibody-mediated rejection:
A case analysis

Robert B. Colvin, Harvard Medical School, Boston, USA

Alloantibodies cause a variety of adverse effects on renal transplants, including chronic antibody-mediated rejection, a new diagnostic category in the Banff system. Recognition and appropriate therapy requires demonstration of characteristic pathology (transplant glomerulopathy, peritubular capillary lesions), C4d in capillaries, and detection of circulating donor-reactive alloantibody (DSA). Therapeutic options are under investigation and will be illustrated in a case presentation. The potential mechanisms of action of rituximab will be discussed, as well as new pharmaceutical approaches to the inhibition of antibody responses.

Case: A 63-year-old white male received a deceased donor renal transplant 15 years previously. Aside from an episode of acute cellular rejection at 2 months, he has been stable. Steroids were discontinued after 7 years, and cyclosporine and azathioprine were reduced after 10 years (250 mg and 50 mg, respectively). His serum creatinine level crept from 1.2 mg/dl (year 6) to 1.6 mg/dl (year 13) and then to 2.5 mg/dl at admission, associated with the appearance of weak class I (A2) DSA. Renal biopsy showed transplant glomerulopathy, duplication of the glomerular basement membrane (GBM) and intracapillary mononuclear cells.
Mononuclear cells were also in peritubular capillaries, which stained diffusely for C4d. Arteries and arterioles were normal. Electron microscopy showed GBM duplication and mesangial cell interposition. Peritubular capillaries had circumferential basement membrane multilamination (>7 layers). Treatment consisted of switching to tacrolimus, mycophenolate mofetil, and a course of rituximab, without plasmapheresis. His serum creatinine level fell to 1.7 mg/dl, where it has remained for 18 months. His urine total protein to creatinine ratio (TP/Cr) is unchanged at 0.27, and DSA are now undetectable.