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  • Curative treatment for end-stage organ disease
  • Prevalence of transplants ↑ with improved surgical techniques, immunosuppression regimens, & disease state management leading up to transplant
  • Liver: chronic noncholestatic liver disorders (most common reasons for transplant)→ chronic HCV, EtOH, chronic HBV; cholestatic liver disorders → primary sclerosing cholangitis (PSC), primary biliary cirrhosis (PBC); other reasons for transplant → metabolic disorders causing cirrhosis, &/or severe extrahepatic morbidity, primary hepatic malignancies, fulminant hepatic failure, retransplant, NASH (nonalcoholic steatohepatitis)
  • Kidney: DM, HTN, GN, PCKD, hypertensive nephrosclerosis, congenital, familial & metabolic diseases, tubular & interstitial diseases, neoplasms, retransplant
  • Heart: CAD, cardiomyopathy, congenital heart disease, valvular heart disease
  • Lung: emphysema/COPD, cystic fibrosis, idiopathic pulmonary fibrosis, α1-antitrypsin deficiency, idiopathic pulmonary arterial hypertension, congenital disease
  • Pancreas: type 1 DM complicated by severe hypoglycemia unawareness or hyperlability
  • Intestine: short gut syndrome, functional bowel problem

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Figure 46-1.
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Immunosuppression site of action on T cell. (Modified with permission from Mueller XM: Drug immunosuppression therapy for adult heart transplantation. Part 1: immune response to allograft and mechanism of action of immunosuppressants, Ann Thorac Surg 2004 Jan;77(1):354.)

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Immunosuppression

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Induction Immunosuppression

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(Drugs 2007;67:2667; AJHP 2011;68:211)

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  • Treatment goals: prevent acute rejection; delay initiation of nephrotoxic agents (calcineurin inhibitors)
  • Antithymocyte globulin (rabbit) (rATG): polyclonal antibody that binds to various lymphocyte CD markers & labels immune cells for destruction; used off-label in U.S. for induction therapy in any solid organ transplant; depletes affected cell w/in 24h of 1st dose
  • Basiliximab: inhibits IL-2 binding on CD25 → prevents T-cell replication
  • Alemtuzumab: monoclonal antibody that binds to CD52 on T & B cells labeling them for antibody-mediated cell lysis (Transpl Int 2006;19:705); used off-label for induction therapy; place in therapy still debated

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Clinical Pearl 46-1

Antithymocyte globulin & alemtuzumab are lymphocyte-depleting agents → can lead to profound lymphopenia; they can be used for induction & treatment of rejection; in contrast, basiliximab is nonlymphocyte depleting & is only used for induction therapy & never for treatment of rejection.

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Table 46-1 Biologics Used for Induction or Rejection in Solid Organ Transplantation

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