Version July 2025
IV: intravenous; rATG: rabbit antithymocyte globulin; TCMR: T cell-mediated rejection.
* Treatment of mixed acute rejection involves treatment of both T cell-mediated rejection and acute antibody-mediated rejection. Refer to UpToDate content on treatment of antibody-mediated rejection.
¶ For patients with Banff IB, practice varies among transplant centers. Some experts prefer to treat all patients with Banff IB TCMR with glucocorticoids alone and reserve the use of rATG for those who do not respond to glucocorticoids. Other experts treat with glucocorticoids alone if the patient presents early (≤1 year) after transplant and with rATG plus glucocorticoids if the patient presents later (>1 year) after transplant. There is no high quality evidence for support one of these treatment approaches over another.
Δ In patients who are being administered triple immunosuppressive therapy, we switch to mycophenolate (if they are on azathioprine) or tacrolimus (if they are on cyclosporine). Patients who develop acute rejection while on triple therapy with tacrolimus, mycophenolate, and prednisone should continue these agents at higher doses if possible. We typically start by targeting higher levels of tacrolimus (ie, 5 to 7 ng/mL). In patients who are receiving dual therapy (calcineurin inhibitor and antimetabolite without prednisone) at the time of rejection, we initiate long-term prednisone at 5 mg once daily.
◊ There is no consensus in the management of borderline rejection and whether antirejection treatment should be used. We do not administer specific treatment for rejection but augment maintenance immunosuppression. Other transplant centers choose to treat borderline rejection as acute TCMR, given observational data that a pathological diagnosis of borderline rejection is associated with adverse clinical and histologic outcomes. However, other studies question the utility of rejection treatment in these patients.
§ We typically advocate for inpatient admission for management and administration of IV glucocorticoids. Methylprednisolone is typically administered as 3 to 5 mg/kg IV once daily for 3 to 5 doses (maximum daily dose of 500 mg). Alternatively, for patients with Banff IA TCMR, some transplant centers choose to treat with high-dose oral glucocorticoids (eg, prednisone 80 mg once daily for three days) on an outpatient basis, provided that these patients are able to return for frequent laboratory testing. After the glucocorticoid pulse, we resume the maintenance dose of oral prednisone that the patient had been taking prior to the episode. However, some experts prefer a more gradual taper of oral glucocorticoids after pulse glucocorticoids.
¥ Alemtuzumab is administered as a single intravenous dose of 30 mg. Alemtuzumab is not readily available to all medical centers that perform kidney transplantation. If alemtuzumab is not available, another alternative is horse antithymocyte globulin, if available, which can be given as 15 mg/kg IV once daily for 3 to 7 days.
‡ For Banff IB TCMR, we administer rATG at 1.5 to 3 mg/kg once daily (maximum daily dose of 500 mg) for one to three days for a total dose of 3 to 6 mg/kg in the first transplant year. For Banff II or III TCMR, we administer rATG at 1.5 to 3 mg/kg once daily for three to five days (maximum daily dose of 500 mg) for a total dose of 5 to 10 mg/kg. The total number of doses is determined by the severity of Banff grading. As an example, in patients with Banff IIA TCMR, we would give 2.5 mg/kg daily for two days, and in patients with Banff III TCMR, we would give 2 mg/kg daily for four to five days, depending upon the response in serum creatinine.