Nephrology

451 Treatment of Rejection in Renal Transplant

  • Renal Transplant Rejection

    Rejection episodes usually occur after the first week and are associated with lymphocyte invasion of the graft (acute rejection). Humoral-mediated rejection (antibodies to the graft) occurs in the first week (hyperacute rejection) but is rare because the recipient's serum is screened for antibodies in the crossmatch before the transplant

    There is no effective treatment for hyperacute rejection but the common acute rejection episode can usually be reversed by an increase in immunosuppression

    A confirmed rise in serum creatinine of 0.02 mmol/l or more is taken as a sign of rejection if the rise cannot be explained on other grounds. With moderate and severe rejection episodes the urinary volume falls, the blood pressure rises, body weight increases, and there may be fever. High fever however is more likely due to infection.

    For succesful transplantation, rejection and infection have to be sorted out promptly - results of investigations must be obtained quickly and appropriate therapeutic measures started without delay.

    A routine Transplant Biopsy (as per Biopsy Protocol) is often carried out 3 months after transplantation to assess rejection activity which may not otherwise be clinically apparent.

    Treatment of Acute Rejection

    Standard Oral

     "Pulse Prednisolone  300mg/m2
       200mg/m2
       100mg/m2, on successive days

    Usually the serum creatinine falls after the first or second dose.

    Standard Intravenous

    300 mg IV/m2 Methyl Prednisolone daily intravenously, given over 30 minutes, for 3 days.

    This treatment is used if oral prednisolone cannot be taken or if a 2nd rejection episode occurs soon after an episode which partly responded to oral prednisolone.

    Again the serum creatinine usually falls 24 hours after the first or second dose.

    OKT3
    This is a murine monoclonal antibody which causes rapid lysis of T3 lymphocytes. It is given for rejection episodes unresponsive to steroids.

    Protocol for Administration of OKT3:-

    Preparation

    Acute pulmonary oedema in volume overloaded patients may occur with the first dose of OKT3. Ensure the patient is not volume overloaded by clinical examination and if necessary by chest x-ray. The weight of the patient should be the "dry" dialysis weight. Use lasix to promote a diuresis, restrict fluids and dialysis may be required. Ensure patient's temperature does not exceed 37.8ᄚC - give paracetamol if necessary. Ensure availability of Oxygen, Adrenalin, and Hydrocortisone.

    1. Pre-medication (required only for first 2 doses)
      30 minutes prior to administration give
      • methylprednisolone, 1 mg/kg IV
      • promethazine (Phenergan), 0.4 mg/kg IV, and
      • oral Paracetamol

    2. Administration
      Draw up OKT3 (1 ampoule = 5 mg) through a low protein -binding filter (available in Pharmacy). Administer drug in a bolus IV injection in less than 1 minute. For children under 20 kg body weight give 2.5-5 mg OKT3, for patients over 20 kg give 5 mg.

    3. Post Administration Procedure (first 2 doses only)
      Record pulse, blood pressure, temperature and respiration rate at 15 and 30 minutes, then half-hourly for 2 hours, then hourly for 6 hours. 30 minutes after administration of OKT3, give Hydrocortisone, 50-100 mg IV.

      Maintain venous access for 6 hours.

    4. Management of Adverse Reactions
      Fever - give additional paracetamol as required
      Respiratory Effects - may need additional hydrocortisone, adrenalin, oxygen, or salbutamol.
      Acute Pulmonary Oedema - may need intubation, ventilation and dialysis to remove water.

    5. Concomitant Immunosuppression
      Cease Cyclosporin during administration of OKT3; resume 3 days prior to completion of course.
      Continue full doses of azathioprine and prednisolone.

    6. Duration of Course
      Usually 10-14 days of daily injections.

    7. (viii) Late Sequelae
      Consider possibility of opportunistic infections, especially CMV and herpes simplex. Ensure patient is on Acyclovir and Bactrim during OKT3. Gancyclovir (5mg/kg b.d. for 1st week then 5 mg/kg/day after 1st week) may be needed for CMV infection induced by OKT3.

    1. ATGAM (Antithymocyte Globulin)
      How it works:
      This drug acts to help control rejection by lowering the T-cells. It is a Gamma-globulin derived from HORSES. It may be used immediately post-operative or at other times in order to control rejection.

      Dose:
      A test dose is given first via an intra dermal injection.
      Dose: 0.1ml diluted 1:100 with 0.9% saline.

      If a marked well or flare reaction occurs at the injection site within the next 15 minutes, hypersensitivity to the used protein exists.

      In a rejection - as per drug information.
      Compatible with 5% dextrose and 0.9% saline.

      Administer over 1 hour.
      May be given via peripheral or central line.
      Discard ampoule immediately.

      Side Effects:
      Generally very well tolerated and side effects are usually mild. Nausea and/or vomitting and headache are most common.

      Nursing Actions:
      Continuous clinical monitoring of patient during treatment is vital, in order to reduce risk of anaphylactiod reactions.

      Drugs to be kept in room:
      Adrenaline 1:1000x1
      Adrenaline 1: 10,000 x
      Methyl prednisolone 500mgs x 2
      Phenergan 50mgs x 5

      ** Appropriate size airway also to be kept by patients bed.

      Parameters to be monitored:
      Heart rate
      Respiratory rate
      Blood pressure
      Temperature
      1/2 hourly
      1/2 hourly
      hourly
      2 hourly
      Throughout infusion

      Report:
      Over/Under infusion of drug
      Tachycardia
      Hypotension
      Increase in temperature

      Observe:
      IV site
      Skin condition (rash)

      * Daily control of the blood count - serum levels of T-cells
      * Sterile procedure when drawing up and attending to CVC infusions. 2 persons non-touch technique when peripheral IV in-  situ.

    2. Conversion to Tacrolimus - refer to Section 2.3(c)

      Failure to respond to steroid medication.

      Either options 3 (OKT3), 4 (ATGAM) or 5 (Conversion to Tacrolimus) can be used depending on the circumstances.