Induction Therapy in Kidney Transplantation - Summary

Most kidney transplant centers in the United States utilize induction agents as part of their immunosupression protocols. The reasoning behind is that induction therapy has been shown to reduce the rate of acute rejection, however no trial has yet demonstrated an improvement in long-term graft survival.  Induction therapy has also expanded in centers using steroid-withdrawal protocols and in patients with expected delayed graft function due to prolong ischemia time (ECD/DCD kidneys), since calcineurin inhibitor initiation may be delayed (significant vasoconstriction from CNI may potentially delay recovery).

Rabbit antithymocyte globulin (rATG or Thymoglobulin) is the most common agent used in more than 55% of transplant cases in the USA, despite not being FDA-approved for this use (only for treatment of severe cellular rejection). Curiously, rATG is prepared by immunizing pathogen-free

rabbits with a cell suspension of human thymic tissue (thymocytes). After immunization, the serum is harvested from rabbits and immunoglobulins against thymocytes are isolated and subjected to a number of purification processes. Samples from more than 26,000 immunized rabbits are pooled to achieve a high level of batch-to-batch consistency!

Our center uses ATG for induction in high immunological risk patients and Basiliximab for low risk patients in combination with tacrolimus and MMF for maintenance. Steroid withdrawal is performed on most patients by the end of first week post-transplantation, with the exception of highly sensitized patients.

Below a summary table of the 3 most common induction agents in clinical use today, their target cells, dose, cost and side effects.

Antibody	Brand	Class	Lymphocyte depleting	Antigenic Target and Cells	Typical prescription	Side effects
Basiliximab	Simulect (Novartis)	Monoclonal	No	IL2 receptor (CD25)   Activated T cells	20mg x2 doses  U$4,254	Hypersensitivity reaction (rare)
Rabbit antithymocyte globulin	Thymoglobulin (Genzyme)	Polyclonal	Yes	Multiple Ag   Mainly T cells, to a lesser extent B and NK cells	1.5mg/kg 3-7 doses  U$7,824-18,256 Premedicate with steroids and Tylenol Decrease dose if WBC<3 or="" ptls="" span="">	Fever, chills, dyspnea, nausea, diarrhea, headache, general pain and pulmonary edema (cytokine release syndrome)
Alemtuzumab	Campath 1H (Berlex Laboratories)	Monoclonal	Yes (more prolonged)	CD52 Ag T, B and NK cells, monocytes, macrophages, dendritic cells, eosinophils, mast cells	30mg x1 dose  U$2,065	Generally none when given subcutaneously

More details about the use of induction therapy in transplantation on this prior blog