B50. Basic principles of immunosuppressive treatment following organ transplantation.

Following organ transplantation, lifelong immunosuppression is required to prevent transplant rejection. Modern post-transplant immunosuppressive therapy has reduced the incidence of rejection to < 10%. It’s important to individualise the choice and dose of immunosuppressants to achieve adequate immunosuppression as well as the least amount of side effects and complications. This is very difficult as there is no biomarker for adequate immunosuppression. It’s usually best to err at the side of giving too much immunosuppression, rather than risking an organ.

Complications

Chronic immunosuppression increases the risk for infections, cardiovascular disease, diabetes mellitus, and malignancy. Common infections include candidiasis, PCP, BK polyomavirus infection, JC polyomavirus infection, CMV, EBV, and tuberculosis.

Common malignancies include non-Hodgkin lymphoma, nonmelanoma skin cancer, and virally induced cancers like Kaposi sarcoma, HCC, and vulvar carcinoma. Patients must be annually screened for these malignancies.

Cardiovascular disease is a major cause of death and graft loss, and so modifiable risk factors for CVD must be addressed.

Kidney transplant immunosuppression

Generally, the immunosuppression consists of an initial induction therapy followed by maintenance. Induction usually consists of methylprednisolone + another drug, which may be basiliximab (anti-IL2), antithymocyte globulin (ATG), rituximab, or IVIG.

Maintenance therapy usually consists of prednisolone, tacrolimus, and mycophenolate mofetil. Calcineurin inhibitors like tacrolimus are considered the most important component of kidney transplant immunosuppression.

The serum concentration of these immunosuppressant drugs should be regularly monitored to ensure them being in the therapeutic window.

Liver transplant immunosuppression

A calcineurin inhibitor, especially tacrolimus, is the most important component of liver transplant immunosuppression. Other components include corticosteroids and mycophenolate mofetil. These are generally started postoperatively and then tapered down and discontinued after a few months as part of induction therapy. If calcineurin inhibitor-induced nephrotoxicity is a concern, the mTOR inhibitor sirolimus may be used instead of calcineurin.

Unlike kidney transplantation, liver transplantation may not require lifelong immunosuppression. Some physicians will give stable and low-risk patients an option of an immunosuppressant-free trial period, which, if successful and without rejection, may be lifelong but continuously monitored.

Antimicrobial prophylaxis

Patients should receive antibiotic, antiviral, and in some cases antifungal prophylaxis for the first 6 months after transplant. This includes TMP-SMX for PCP, antivirals for HSV, HZV, and CMV, as well as inactivated vaccines for influenza, pneumococcus, and hepatitis B.