Improving Long-term Graft Survival: Nephrotoxicity, Infections, and Other Complications of Immunosuppressive Therapy*

The incidence of posttransplantation comorbidities related to use of immunosuppressive agents is extremely high. As rates of survival have progressively improved after heart transplantation, the implications of these treatmentrelated comorbidities on long-term health, patient survival, and healthcare costs have become clear. This article reviews the major nonvasculopathy complications of immunosuppressive therapy, including hypertension, metabolic abnormalities, infection, malignancy, and renal insufficiency. Several strategies aimed at minimizing side effects of immunosuppressive regimens (such as limitation of calcineurin inhibitor [CNI] use) are described. Although newer agents, such as the proliferation signal inhibitors, appear to have beneficial effects in limiting comorbidities, especially of nephrotoxicity in CNI-sparing protocols, the full therapeutic profile of these agents has yet to be defined. (Adv Stud Med. 2008;8(6):196-201) D espite progressive improvements in cardiac transplant outcomes, significant morbidities persist, including hypertension, metabolic abnormalities, infection, malignancy, renal insufficiency, and cardiac allograft vasculopathy (CAV). Many of these complications are mediated by specific immunosuppressants or via synergistic toxicities between agents. In particular, the calcineurin inhibitors (CNIs) cyclosporine and tacrolimus are known to have significant adverse impacts on renal function and cardiovascular disease in solid organ transplantation. New immunosuppressants offer the possibility of enhanced efficacy with less toxicity, but clinicians need to maintain an awareness of all potential complications that limit long-term survival and cause morbidity. This article and the ensuing discussion highlight the nonvasculopathy complications of immunosuppressive therapy and describe evolving strategies for managing the main comorbidities associated with the complex multidrug regimens in use today.