ATG vs simulect as induction for kidney transplant

Chronic graft vs host disease is a leading cause of late morbidity and mortality. ATG is an antibody that was introduced 30 years ago to prevent rejections of grafts.

ATG ( Antilymphocyte immunoglobulins):

Researchers hypothesize that giving ATG is part of preparation for transplantation with decreased chronic graft vs host disease. It has been used in various doses in various timings in both pediatrics in adults. The dosing and pharmacokinetics is very variable in various patients. Below 40 years, the two predictors of ATG are weight and absolute lymphocyte count and above the weight over40 kgs it’s only absolute lymphocyte count. ATG is a mixture of non-specific antilymphocyte immunoglobulins that target not only T cell subsets but also a variety of other immune and non-immune cells, making its precise immunoglobulin composition difficult to compare from one preparation to the next.The inclusion of ATG to the standard myeloablative regimen for allogeneic transplantation resulted in a significant reduction in chronic graft vs host disease without increasing infections or relapses. So dosing ATG in children and the adult population is probably not to do by weight but also by absolute lymphocyte counts. ATG particularly in the context of unrelated donors renal transplantation is associated with a lower rate of graft rejection, graft diseases although no overall benefit in survival of diseased patients is observed. It is a monoclonal antibody and it’s not a normal regular drug where we know how much we are giving. Anti-thymocyte globulin (ATG) is an infusion of antibodies derived from horses or rabbits against human T cells and their synthetic analogues (thymocytes), which is used in the prevention and treatment of acute rejection in organ transplantation as well as the treatment of aplastic anemia. ATG treatment is simple; it is injected into a 1000ml bag of normal saline, attached to the patient’s picc line or Hickman line, and runs for about 12 hours a day for four days. A small dose over an hour before the first full bag because some people may be allergic to it. Different patients must have different levels of exposure related to age, their weight and more importantly depending on their lymphocyte count. Patients who are underexposed are at much higher risk of developing graft associated diseases or graft rejection whereas patients with higher dose or overexposure who have significant count or ATG after donor cells are introduced, can have higher risk of infections. Administrating ATG prior to graft transplantation lowered the incidences of graft rejection. 

Basiliximab or commercial simulect:

It’s a monoclonal antibody prescribed to prevent rejection of the transplanted organ by decreasing the activity of the immune system. Basiliximab is popularly known as simulect . Basiliximab blocks the interleukin present on T cells , which blocks cell mediated rejection of the transplanted organ. Basiliximab belongs to a group of drugs. Basiliximab is available in the following terms, powder for injection. Basiliximab is available in the following strengths: 10 mg, 20 mg vials. Reconstituted as a solution for injection and is administered through a vein.The usual dose is 20mg to be given within 2 hours before transplantation. It has to be repeated for four days. The side effects of Basiliximab include pain in the abdominal region, cough, dizziness and fever, weakness, painful urination,shortness of breath, sore throat,swelling of ankle,body, face, feet or lower legs, shaking of the hands or feet, vomiting,white patches on mouth, throat and tongue.

Caution should be taken in patients with allergic reactions, depressed patients (suicidal tendency), acute infections, pregnancy , breastfeeding, diabetic ptients, Drug interacion can cause or enhance the effect of the drug, decrease the effect of the drug, a new side effect can arise. Basiliximan can interact with other drugs like adalimumab, baricitinib, efalizumab, infliximab. Basiliximab is a monoclonal antibody that binds to the chimeric anti-interleukin-2 receptor. Basiliximab is a glycoprotein that was created using recombinant technology. It is used to protect white blood cells from rejection during acute renal transplantation. 

Pharmacodynamics: Basiliximab inhibits the IL-2 receptor. It specifically inhibits IL-2-mediated lymphocyte activation, a key pathway in the cellular immune response involved in allograft rejection.

Action mechanism: Basiliximab is a glycoprotein that was created using recombinant technology. It is used to protect white blood cells from rejection during acute renal transplantation. It binds and inhibits the alpha chain of interleukin-2 receptors (IL-2R alpha), also known as CD25 antigen, on the surface of activated T lymphocytes. Basiliximab binds to the alpha-subunit (CD25) of the high-affinity IL-2 receptor with high affinity. This prevents IL-2 binding, which in turn prevents T-cell activation and prevents the body from mounting an immune response against the foreign kidney.

Simulect® should be administered as a bolus injection or diluted to a volume of 25 mL (10 mg vial) or 50 mL (20 mg vial) with normal saline or dextrose 5 percent and infused intravenously over 20 to 30 minutes. Basiliximab, the active ingredient, is water soluble. Simulect (basiliximab) is a sterile lyophilisate that comes in 6 mL colorless glass vials and is available in 10 mg and 20 mg strengths.

The recommended regimen for adult patients is two doses of 20 mg each. The first 20-mg dose should be administered no later than 2 hours before transplantation surgery. The second 20-mg dose should be administered four days after transplantation. If complications such as severe hypersensitivity reactions to Simulect or graft loss occur, the second dose should be withheld.

The recommended regimen for pediatric patients weighing less than 35 kg is two doses of 10 mg each. The recommended regimen for pediatric patients weighing 35 kg or more is two doses of 20 mg each. The first dose should be administered within 2 hours of transplantation surgery. The second dose should be administered four days after transplantation. If the first dose is missed, the second dose should be skipped.

If hypersensitivity or any other complications occur. 

Conclusion: Both ATG and simulect are still intriguing and potent tools for preventing and treating acute rejection in renal transplantation, particularly in highly immunized patients. Before using this powerful immunosuppressive drug, an individual risk–benefit analysis should always be performed . Future research should concentrate on the development of immunologically standardized biomarkers that can be routinely determined prior to transplantation and can assess the risk associated with the use of depleting cell antibodies as induction therapy.