Kidney Transplantation Induction Quiz Answers

Alemtuzumab	A. This anti CD25 human/ mouse chimeric antibody is almost devoid of side effects. It does not increase the risk for malignancies or infections.
Rituximab	B. This antibody has been used in a recent trial to facilitate positive crossmatch transplantation in living donors by blocking the effector pathway of antibody mediated allograft injury.
Thymoglobulin	C. This agent is used to treat antibody mediated rejection and as induction in sensitized individuals. It decreased the production of anti-HLA antibodies by targeting the CD 20 receptor on B cells and plasma cells.
Daclizumab	D. This antibody targets CD 52. It is FDA approved for the treatment of CLL. It is often used in minimization protocols for kidney transplantation.
Basiliximab	E. This agent when used as an induction agent may increase the risk of cellular rejection.
Atgam	F. This polyclonal antibody preparation targets many different receptors on T cells. It increases the risk of PTLD, and CMV compared to no induction or anti-CD25 induction. However, it has been shown to be a superior agent in reducing rejection episodes and prolonging graft survival especially in high risk individuals.
OK3T	G. This polyclonal antibody preparation came from horses. It has since been largely replaced by another polyclonal T cell preparation.
Eculizumab	H. This agent was a humanized monoclonal antibody that targeted the alpha chain of the IL-2 receptor of T-cells. The manufacturer discontinued its use in January 2009.
	I. This monoclonal antibody against the T-cell receptor was the first such antibody used for any clinical indication in the United States. Its current use has been minimized due to severe adverse reactions including serum sickness and pulmonary edema.

Answers:

Alemtuzumab: D Alemtuzumab is FDA approved to treat CLL. It targets CD 52 and results in B and T cell depletion. It has been used as an agent to facilitate steroid free transplantation, and had similar outcome to Thymoglobulin in the recent INTACT trial (N Engl J Med. 2011 May 19;364(20):1909-19. PMID: 21591943).

Rituximab: E Rituximab is a monoclonal anti-CD 20 antibody that targets B cells. It has been used to treat antibody mediated rejection and in desensitization protocols. It does not however, target plasma cells (which is why answer C is incorrect). In non-sensitized patients, Clatworthy et al. found the risk of cellular rejection to be much higher when using rituximab as an induction agent compared to dacillizumab (83% vs. 14%) (N Engl J Med. 2009 Jun 18;360(25):2683-5. PMID: 19535812).

Thymoglobulin: F Thymoglobulin is the most common induction agent used in the USA. It is created by immunizing rabbits with human thymus. This results in a potent polyclonal T cell depleting agent which reduces the risk of rejection but also increases infectious and malignant complications.

Dacilizumab: H

Basiliximab: A Basilizimab and Daclizumab have been shown to reduce the risk of rejection in the first year post transplant (Lancet. 1997 Oct 25;350(9086):1193-8 PMID: 9652559). The anti-rejection effect is not as potent as anti-lymphocyte globulin however, basiliximab does not increase the risk for infections or malignancy.

Atgam: G Atgam has been largely replaced by Thymoglobulin in the U.S.

OKT3: I

Eculizumab: B A recent trial by Stegall et al. found Eculizumab to help abrogate a positive flow cytometry crossmatch in living donor kidney transplantation(Am J Transplant. 2011 Nov;11(11):2405-13. PMID: 21942930). It is FDA approved to treat paroxysmal nocturnal hemoglobinuria (PNH) and works by blocking complement component C5.