**8.1 Infection and malignancy issues**

Opportunistic infections remain an important risk for immunocompromised patient despite the use of prophylactic measures[24]. Exposure to viruses such as Epstein-Barr virus (EBV), cytomegalovirus (CMV), herpes simplex virus, and human papillomavirus place the recipient at risk for infection and, potentially, later malignancy.

The incidence of CMV has been reduced with the use of antiviral prophylaxis in the first 3 months posttransplant. However, preemptive monitoring and initiation of treatment in the case of significant viremia after discontinuation of prophylaxis remains to be proven as a strategy for reducing the risk of late-onset CMV disease. Approximately 27% of patients who die with a functioning graft die from infectious or malignant complications. This highlights issues regarding the appropriate amount of immunosuppression required to balance aspects of graft function with complications related to therapy. An increasingly recognized problem associated with immunosuppression is BK virus nephropathy. This virus, a member of the human papovavirus family, lives in the human genitourinary tract and replicates in some immunosuppressed patients, causing allograft

(5-10 ng/mL) to reduce the risk of nephrotoxicity. Controversy continues regarding the best

These agents are usually combined with a calcineurin inhibitor and include steroids, azathioprine, MMF, and sirolimus. Currently, most protocols use a calcineurin inhibitor and steroids with or without MMF. The use of adjuvant agents allows clinicians to achieve adequate immunosuppression while decreasing the dose and toxicity of individual agents. In kidney transplant recipients, mycophenolate mofetil has assumed an important role in immunosuppression after several clinical trials reported a marked decrease in the prevalence of acute cellular rejection compared to azathioprine; furthermore, a reduction in 1-year treatment failures was also reported for MMF. Ongoing long-term studies suggest

Sirolimus has shown great promise for its potential to combat acute cellular rejection and to provide rescue immunosuppression. Current work shows that sirolimus causes a significant decrease in acute rejection and improvement in patient and graft survival compared to

Clinical immunosuppression strategies involve striking a balance between freedom from rejection episodes and freedom from the toxicity and complications of immunosuppressive treatment regimens. As the number of rejection episodes decreases, the likelihood of

The specific toxicities of the immunosuppressive drugs are described in the sections pertaining to each drug. In general, the goal of multidrug therapy is to decrease the

Opportunistic infections remain an important risk for immunocompromised patient despite the use of prophylactic measures[24]. Exposure to viruses such as Epstein-Barr virus (EBV), cytomegalovirus (CMV), herpes simplex virus, and human papillomavirus place the

The incidence of CMV has been reduced with the use of antiviral prophylaxis in the first 3 months posttransplant. However, preemptive monitoring and initiation of treatment in the case of significant viremia after discontinuation of prophylaxis remains to be proven as a strategy for reducing the risk of late-onset CMV disease. Approximately 27% of patients who die with a functioning graft die from infectious or malignant complications. This highlights issues regarding the appropriate amount of immunosuppression required to balance aspects of graft function with complications related to therapy. An increasingly recognized problem associated with immunosuppression is BK virus nephropathy. This virus, a member of the human papovavirus family, lives in the human genitourinary tract and replicates in some immunosuppressed patients, causing allograft

method to monitor cyclosporine levels.

MMF also reduces the prevalence of chronic rejection.

**8. Complications of immunosuppression** 

**8.1 Infection and malignancy issues** 

opportunistic infections, late malignancy and drug toxicity increases.

toxicities that are seen with higher doses of individual drugs.

recipient at risk for infection and, potentially, later malignancy.

**7.4 Adjuvant agents** 

azathioprine[21, 22].

dysfunction. While antiviral agents such as cidofovir and leflunomide are active against the BK virus, the mainstay of therapy is a reduction in immunosuppression. The risk of acute allograft rejection with dose reduction is currently under investigation.

The most serious long-term effects of immunosuppression are the late malignancies that can develop in transplanted patients[25]. In addition to the post-transplantation lymphoproliferative diseases that are specific to chronically immunosuppressed patients, patients may also develop Kaposi's sarcoma. In addition, patients are at higher risk for malignancies that are common in non-immunosuppressed patients. The most common cancer observed in immunosuppressed patients is skin cancer, which mimics its frequency in the general population. A slightly higher incidence of Hodgkin's disease, non-Hodgkin's lymphoma, and breast, colon, lung, uterine and ovarian cancers has been observed in transplant recipients. For this reason, patients should undergo yearly cancer surveillance, including chest radiography and a general physical examination to look for new skin lesions; Pap smears and pelvic examinations are also suggested for women.
