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KEY CONCEPTS

KEY CONCEPTS

  • imageGenerally, patients receive a combination of two to four immunosuppressive drugs in order to minimize individual drug toxicities as well as block different aspects of the immune response.

  • imageWhile the calcineurin inhibitors (CI) tacrolimus and cyclosporine, inhibitors of interleukin (IL)-2 and thus T-cell activation, are the backbone of immunosuppressive regimens, they are associated with serious adverse effects, primarily nephrotoxicity and neurotoxicity.

  • imageCalcineurin inhibitor-induced nephrotoxicity is one of the most common adverse effects observed in solid organ transplant recipients. Therapeutic drug monitoring is used to optimize the use of calcineurin inhibitors and prevent toxicity.

  • imageCorticosteroids are a key component of most immunosuppressive strategies because they block the initial steps in allograft rejection. Their significant adverse effects have led to steroid-minimizing and steroid-free immunosuppressive protocols. Corticosteroids, however, remain first-line treatment for allograft rejection.

  • imageAzathioprine and mycophenolic acid derivatives inhibit T-cell proliferation by altering purine synthesis. Bone marrow suppression is the most significant adverse effect associated with these agents.

  • imageSirolimus and everolimus inhibit the mTOR (mammalian target of rapamycin) receptor, which alters T-cell response to IL-2. The adverse effects associated with these agents include leukopenia, thrombocytopenia, anemia, and hyperlipidemia.

  • imageAntibody preparations that target specific receptors on T cells are classified based on their ability to deplete lymphocyte counts. Most lymphocyte-depleting antibodies are associated with significant infusion-related reactions, whereas nondepleting agents are generally better tolerated.

  • imageLong-term allograft and patient survival are limited by chronic rejection, cardiovascular disease, infection, and long-term immunosuppressive complications such as malignancy.

  • imageMultiple factors impact immunosuppressant systemic exposure in transplant patients. Recognition of these factors by clinicians will facilitate optimization of drug therapy.

PATIENT CARE PROCESS

Patient Care Process for Solid Organ Transplant Recipient*

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Collect

  • Patient characteristics (eg, age, sex, pregnant)

  • Patient medical history (personal and family)

  • Social history (eg, tobacco/ethanol use/marijuana), dietary habits

  • Current medications including OTC use, herbal products, dietary supplements

  • Objective data

    • Blood pressure (BP), heart rate (HR), respiratory rate (RR), temperature (T), height, weight, O2-saturation

    • Labs including measures of end-organ function, hemoglobin (Hgb), platelets, serum creatinine (SCr), immunosuppressant concentrations, white blood cell count (WBC)

Assess

  • Presence of over immunosuppression: infection, adverse drug events

  • Presence of under immunosuppression: evidence of end-organ compromise

  • Assess risk based on patient-specific risk factors and time posttransplant

Plan

  • Drug therapy regimen including specific immunosuppressive agents, dose, route, frequency, and duration (see Tables 105-3 and 105-4)

  • Monitoring parameters including efficacy (eg, Scr, electrolytes, INR, Total Bili) and safety (eg, sign and symptoms of rejection, CBC, SCr, constitutional symptoms); frequency and timing of follow-up

  • Patient education (eg, purpose of treatment, dietary and lifestyle restriction, drug-specific information, medication administration)

  • Signs and symptoms of rejection (urine output, BP, pain, fever) or infection (temperature)

  • Self-monitoring for sign/symptoms adverse effects (see Table 105-6)

  • Referrals to other providers when appropriate

Implement

  • Provide patient education regarding all elements of treatment plan

  • Use motivational interviewing and coaching strategies to maximize adherence

  • Schedule follow-up (eg, CI concentration, Scr)

Follow-up: ...

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