Polyclonal and monoclonal antibodies for induction therapy in kidney transplant recipients

Abstract

ATG reduces acute rejection but has uncertain effects on death, graft survival, malignancy and NODAT, and increases CMV infection, thrombocytopenia and leucopenia. Given a 45% acute rejection risk without ATG induction, seven patients would need treatment to prevent one having rejection, while incurring an additional patient experiencing CMV disease for every 12 treated. Excluding non-CNI studies, the risk of rejection was 37% without induction with six patients needing treatment to prevent one having rejection.In the context of steroid minimisation, alemtuzumab prevents acute rejection at 1 year compared to ATG. Eleven patients would require treatment with alemtuzumab to prevent 1 having rejection, assuming a 21% rejection risk with ATG.Triple maintenance without induction therapy compared to alemtuzumab combined with ESW had similar rates of acute rejection but adverse effects including NODAT were poorly documented. Alemtuzumab plus steroid withdrawal would cause one additional patient experiencing CMV disease for every six patients treated compared to no induction and triple maintenance, in the absence of any clinical benefit. Overall, ATG and alemtuzumab decrease acute rejection at a cost of increased CMV disease while patient-centred outcomes (reduced death or lower toxicity) do not appear to be improved.

Cytolytic Induction Therapy Improves Clinical Outcomes in African-American Kidney Transplant Recipients

“…1,2 Before the advent of antibody preparations, clinicians utilized lymph depletion, high-dose intravenous corticosteroids, and high doses of other immunosuppressants as induction therapies. 3–5 From the 1990s onward, induction therapy in transplantation is typically thought of as using mono or polyclonal antibody preparations given perioperatively.…”

“…High immunologic risk patients may benefit from more intense induction therapy preparations, such as the cytolytic agents. 1,2 The use of the non-T-cell depleting agents [IL-2 receptor antagonist (IL-2 RA) preparations] is still popular choices within kidney transplantation, but is generally recommended for use in lower immunologic risk patients. 6–8 …”

Induction immunosuppression agents as risk factors for incident cardiovascular events and mortality after kidney transplantation

“…19 Both CMV exposure and posttransplant CMV replication contribute to the increased risk of cardiovascular disease in transplant recipients. 19 Both CMV exposure and posttransplant CMV replication contribute to the increased risk of cardiovascular disease in transplant recipients.…”

“…[13][14][15][16][17][18][19] Acute rejection after kidney transplantation is a risk factor for CVEs. Induction agents can be lymphocyte depleting, such as anti-thymocyte globulin (ATG) and alemtuzumab (AZM), or can prevent lymphocyte activation and replication, such as IL-2 receptor antagonist (IL-2RA).…”

Tailor-Made Induction Therapy in ‘Low Risk’ Renal Transplants; A South Asian Perspective

“…The commonly used induction agents include monoclonal antibodies; mAb (muromonab-CD3, daclizumab, basiliximab, alemtuzumab) and polyclonal antibodies; pAb (ATG [equine / rabbit]) [22,23]. These are further classifi ed based on their effect on the host T cells; T cell depleting agents (alemtuzumab, ATG, and muromonab-CD3) and T cell non-depleting agents (basiliximab and daclizumab) ( Table 2).…”