Study purpose: We evaluated short-term clinical and immunological outcomes of kidney transplant recipients who received alemtuzumab induction and a steroid-avoidance protocol.

Methods: This is a retrospective cohort study including all adult first kidney transplant recipients who underwent transplantation at McGill University Health Centre Sept 2011 to Dec 2013. These CDC crossmatch negative patients were induced with alemtuzumab 30 mg and 500 mg of methylprednisolone, followed by dual-agent maintenance therapy with tacrolimus and mycophenolate mofetil. This regimen replaced a previous protocol using thymoglobulin induction and triple maintenance therapy with a calcineurin inhibitor, mycophenolate mofetil, and low-dose prednisone. Prospective screening for donor specific antibodies (DSA) using solid phase assays was conducted at 1-, 3-, 6-, 12-months and annually thereafter. Study endpoints were time to DSA development, biopsy-proven rejection and graft failure. Antibody-mediated rejection (AMR) was treated with plasmapheresis, IvIg, and rituximab.

Results: Of 107 eligible patients, 14 (13.1%) developed DSA within a median of 6 months (interquartile range: 2, 7). Nine (8.4%) developed de novo DSA and 5 (4.7%) without DSA at transplantation had recurrence of historical DSA. Class I, class II and both class I and class II DSA were identified in 5 (35.7%), 5 (35.7%) and 4 (28.6%) of DSA+ patients, respectively. Among DSA- patients, 36 had at least 1 allograft biopsy (12/36 surveillance; 24/36 for cause). DSA+ patients mainly underwent biopsies for-cause (10/14 or 71.4%) and all were diagnosed with AMR/TG. TG alone appeared in 5/93 (5.3%) DSA- patients. Five (35.7%) DSA+ patients experienced cellular rejection prior to (2 patients) or concurrently with AMG/TR (3 patients). Cellular rejection occurred in 9.6% of DSA- patients. Non-adherence, medication errors, and physician-initiated dosage reduction preceded DSA appearance. To date, 3 DSA+ patients (21.4%) and only 1 (1.1%) DSA- patient experienced allograft failure.

Conclusion: Incidence of cellular rejection remained low following the implementation of an alemtuzumab induction and a steroid-avoidance protocol. Greater pre-transplant immunological risk (i.e. documented historical DSA) and/or under-immunosuppression often preceded DSA appearance. Excess allograft failure in DSA+ patients underscores the importance of medication adherence and adequate drug dosing for the prevention of allograft loss.

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