New developments in the management of kidney transplant patients
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New Developments in the Management of Kidney Transplant Patients. Christine E. Chamberlain, Pharm.D., BCPS Clinical Center Pharmacy Department 10/23/01. End Stage Renal Disease. Options for patients with renal disease: Peritoneal dialysis Hemodialysis Kidney transplantation

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New Developments in the Management of Kidney Transplant Patients

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New Developments in the Management of Kidney Transplant Patients

Christine E. Chamberlain, Pharm.D., BCPS

Clinical Center Pharmacy Department


End Stage Renal Disease

  • Options for patients with renal disease:

    • Peritoneal dialysis

    • Hemodialysis

    • Kidney transplantation

      • Living Donor (related and unrelated)

      • Cadaveric Donor

  • Approximately 222,000 patients were receiving hemodialysis (1999 US Renal Data System Report)

  • Only 9000 cadaveric kidney transplants performed in 1999

  • Approximately 4000 living donor transplantations per year

  • In the year 2000, more than 45,000 patients receiving dialysis were awaiting cadaveric kidney transplantation

Am J Kidney Dis 1999;34(Suppl 1)

Cause of End Stage Renal Disease Among New Patients on Hemodialysis in 1997





Am J Kidney Dis 1999;34(Suppl1)

Factors Determining Transplantation Outcomes

  • Type of donor (cadaveric vs. living)

  • Matching and sensitization

    • HLA match (0 antigen mismatch > 6 antigen mismatch)

    • Negative crossmatch

  • Racial Differences

  • Recipient Age

  • Donor Age

  • Other Factors (delayed graft function, cold ischemia time, acute rejection, chronic rejection, years on dialysis, diseases leading to ESRD)

History of Kidney Transplantation


  • First successful kidney transplant

  • Total body irradiation for immunosuppression

  • Steroids


  • Azathioprine


  • Polyclonal anitbodies – anti-lymphocyte globulin (now Atgam, Thymoglobulin)


  • Cyclosporine (Sandimmune ), “triple drug therapy”

  • Monoclonal antibody, OKT3 (Orthoclone ) in 1985

Basics of Immunosuppression

  • Immune system distinguishes self from non-self

  • Antigen: anything that can trigger an immune response

  • B-cell (lymphocyte) – secretes antibodies, presents antigen to T-cell

  • T-cell (lymphocyte), secretes cytokines (ex. IL-2), directs and regulates immune responses, also attacks infected, cancerous or foreign cells

Basics of Immunosuppression

  • Cytokines are chemical messengers – bind to target cells, encourage cell growth, trigger cell activity, direct cell traffic, destroy target cells, and activate phagocytes (“cell eaters”)

  • IL-2 activates T-cells and causes proliferation

  • T-cell surface markers (CD3, CD25, CD52 and T-cell receptor) CD=cluster of differentiation of T-cells

T- Lymphocyte Activation

  • Three signals involved in T-cell activation

  • Calcineurin is activated and induces cytokine genes and T-cell activation genes

  • IL-2 binds to IL-2 receptor which in turn activates Target of Rapamycin (TOR) and promotes T-cell proliferation

  • De novo synthesis of purines is necessary for B and T cell proliferation

Management of a Transplant Recipient

  • Induction Therapy: administer medications that provide marked suppression prior to and during the first week post transplantation, some agents can also block B-cell mediated rejection

  • Maintenance Therapy: administer immunosuppressive agents continuously to prevent acute rejection

  • Administer medications to induce Tolerance?

What is Tolerance?

Immunologic unresponsiveness by the recipient to the kidney graft in the absence of maintenance immunosuppression.

Goals of Transplant Research

  • Prevent rejection and kidney graft loss

  • Reduce the amount of immunosuppression

    • Decrease side effects

    • Decrease toxicity and long term effects

  • Enhance long term patient and graft survival

  • Provide reasonable cost effective therapy

  • Improve patient adherence and quality of life

  • Induce Tolerance (no long term medications, reduces adverse effects, improves quality of life)

Immunosuppressant Discoveries 1990-2000

Tacrolimus (Prograf)

Mycophenolate Mofetil (Cellcept )

Basiliximab (Simulect )

Cyclosporine Microemulsion (Neoral )

Daclizumab (Zenapax )

Rabbit Antithymocyte globulin (Thymoglobulin )

Sirolimus (Rapamune )

How are we doing?One Year Survival Rate Percentage Living vs. Cadaveric

Calcineurin inhibitors



Purine synthesis inhibitors


Mycophenolate mofetil



Target of Rapamycin inhibitor


Polyclonal antibodies (bind several CD’s)

Thymoglobulin 

Atgam 

Monoclonal Antibodies

Blocks Il-2 receptor



OKT3 (anti-CD3)

Modes of Action of Currently Available Immunosuppressants

Graft Half-life in Years

Trends in Immunosuppression

  • Steroid sparing regimens, and steroid avoidance

  • Reducing calcineurin inhibitor dose after critical post transplant period

  • Calcineurin inhibitor avoidance

  • Single drug regimens

Agents on the Horizon

  • Campath 1H (anti-CD52) – lymphocyte and monocyte depleting agent

  • Deoxyspergualin – blocks maturation of T and B cells

  • Everolimus – TOR inhibitor like sirolimus

  • FTY-720 – reversible depletion of lymphocytes from peripheral blood (migration to spleen)

  • CTLA4-Ig – blocks T-cell activation

Other New Developments in Kidney Transplantation

  • Laparoscopic kidney donation

    • Advantages: less post operative pain, shorter hospital stay, minimal scarring

    • Disadvantages: impaired early graft function, graft loss or damage, longer operative time

  • Improved surgical techniques and storage of the kidney graft

  • New antibiotics to treat and prevent opportunistic infections (new antifungals, oral ganciclovir and valganciclovir)

Current Trials at NIH

  • Sirolimus Monotherapy to Optimize Activation Induced Cell Death (AICD) in Renal Transplants Following Lymphocyte Depletion Induction with Thymoglobulin

  • Tolerance Induction Following Human Renal Transplantation Using Treatment with a Humanized Monoclonal Antibody Against CD52 Campath1-H

  • Renal Allotransplantation for the Treatment of End Stage Renal Disease in the Setting of Human Immunodeficiency Virus (HIV) Infection

Role of the Transplant Pharmacist

  • Disease state management

    • Hypertension

    • Diabetes Mellitus

    • Osteoporosis

    • Hyperlipidemia

    • Electrolyte abnormalities

  • Patient understanding and adherence to the drug regimen

  • Pharmacokinetic drug level monitoring

  • Drug interactions (esp. with immunosuppressants)

  • Adverse drug reaction monitoring

Kidney Transplant

  • View a kidney transplant at:


    • Click on clinical folios

    • Click on abdomen

    • Click on kidney transplant

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