The American Society of Transplantation

In order to address your concerns, a kidney transplant biopsy must be performed. The National Consensus Conference To Assess Antibody-mediated Rejection (AMR) in Solid Organ Transplantation recognizes three stages of humoral alloreactivity in which patients present with donor specific antibody (DSA) and no evidence of graft dysfunction: I. Latent humoral response – in which only DSA is present and no evidence of graft injury is documented in the biopsy. II. Silent humoral rejection – in which the patient presents with both DSA and C4d deposition in the peritubular capillaries (PTC) but no evidence of tissue injury. III. Subclinical humoral rejection – in which the patient has detectable DSA, C4d deposition in the PTC, and evidence of tissue injury by light microscopy. Since staging requires a kidney transplant biopsy for proper diagnosis and treatment, in your case scenario, therapeutic decision-making is not possible. The experience acquired through the protocol biopsies studies published by Mayo Clinic and Johns Hopkins supports the treatment of patients in stages II and III [1-3]. Patients in these categories would likely develop overt AMR or transplant glomerulopathy (TG) and interstitial fibrosis and tubular atrophy (IFTA) if left untreated. To date there is no standard of care treatment for these patients, and the majority of transplant centers have developed yet not published their own protocols. In my practice, treatment is dictated by the severity of histology and the presence of chronic and irreversible injury. In the absence of glomerulitis, capillaritis or severe TG and IFTA, my choice of treatment would include heightening of maintenance immunosuppression and IVIg 100 mg/kg weekly for four weeks. In the presence of glomerulitis, capillaritis or any form endothelial cell injury, I would favor the use of plasmapheresis, and low dose IVIg. Recent data from Lefaucheur and collegues [4] suggest that the use of 2 standard doses of rituximab in combination to plasmapheresis and low-dose IVIg may improve graft outcomes and reduce DSA levels more effectively at 3 months. 1. Haas M, et al., Subclinical acute antibody-mediated rejection in positive crossmatch renal allografts. Am J Transplant, 2007. 7(3): p. 576-585. 2. Haas M, et al., C4d and C3d staining in biopsies of ABO- and HLA-incompatible renal allografts: correlation with histologic findings. Am J Transplant, 2006. 6: p. 1829-1840. 3. Gloor JM, et al., Transplant glomerulopathy: subclinical incidence and association with alloantibody. Am J Transplant, 2007. 7: p. 2124-2132. 4. Lefaucheur C, et al., Comparison of Combination Plasmapheresis/IVIg/Anti-CD20 Versus High-Dose IVIg in the Treatmentmof Antibody-Mediated Rejection. Am J Transplant, 2009. 9: p. 1099-1107. 5. Carson KR, et al., Progressive multifocal leukoencephalopathy after rituximab therapy in HIV-negative patients: a report of 57 cases from the Research on Adverse Drug Events and Reports project. Blood, 2009. 113(20): p. 4834-4840.