Cardiovascular Toxicities of Immunosuppressive Agents

Abstract

Cardiovascular disease is one of the major causes of morbidity and mortality following solid organ transplantation. Many of the current immunosuppressive drugs are associated with an increase of one or more risk factors for the development of atherosclerosis. This review compares the mechanism by which individual immunosuppressive agents may impact on these risk factors and the differential contribution of cyclosporine, tacrolimus, mycophenolate, azathioprine, and Rapamycin to these individual risk factors. Attention to the potential cardiovascular toxicities of individual immunosuppressive agents may help design strategies for maintenance of immunosuppression tailored to individual patients.

Belatacept-versus Cyclosporine-Based Immunosuppression in Renal Transplant Recipients with Pre-existing Diabetes

“…Diabetic transplant recipients are at increased risk for cardiovascular disease (2,3) and exhibit higher mortality (1,4 -6) and reduced graft survival (7,8) compared with nondiabetic transplant recipients. Current therapies for maintenance immunosuppression have adverse effects on BP (9,10), lipids (9,10), and glycemic control (11)(12)(13)(14)(15) in RTR, thus contributing to increased cardiovascular morbidity and mortality. More selective immunosuppressive therapies without the cardiovascular and metabolic toxicities of current therapies may therefore improve outcomes in diabetic RTR.…”

Immunosuppression Minimization

“…In a recent single-center study, cardiovascular events and malignancy were the most common causes of death after 5 yr of transplantation in patients with a functioning kidney (8). While there are differences in the side effect profile between cyclosporine and tacrolimus, therapy with CNI contributes to several cardiovascular risk factors, including hypertension, hyperlipidemia, and metabolic abnormalities such as hyperglycemia and hyperuricemia (9). In addition, nephrotoxicity from CNI may also contribute to cardiovascular disease.…”

“…However CNI-based immunosuppression is associated with complications that result in posttransplant morbidities that may limit further improvement in long-term outcome (8,9). While nephrotoxicity has been amply documented and is frequently cited as the Achilles' heel of the CNI representing toxicity-limiting efficacy, the proof of inexorable progression of CNI-induced nephrotoxicity remains controversial (28 -31) In a recent review of data from the Scientific Registry of Transplant Recipients, Ojo et al (30) reported that 15.7% of recipients of extrarenal organs developed renal insufficiency within 5 yr of transplantation.…”

Development of a two‐step chromatography procedure that allows the purification of a high‐purity anti‐histone H1 monoclonal immunoglobulin M antibody with immunosuppressant activity

“…nephrotoxicity (Platz et al, 1994), cardiovascular disease (Miller, 2002) and cancer progression (Hojo et al, 1999). Therefore, the development of a novel immunosuppressant with less patient burden has eagerly been awaited.…”