Calcineurin inhibitors and post-transplant hyperlipidaemias

Abstract

Cardiovascular disease is now the leading cause of death in transplant recipients. This is due, in part, to the vulnerability of these patients to a complicated set of conditions including hypertension, diabetes mellitus, and post-transplant hyperlipidaemia (PTHL). PTHL is characterised by persistent elevations in total serum cholesterol, low density lipoprotein cholesterol and triglyceride levels. The causes of PTHL are complex and not fully understood, however several classes of immunosuppressants including the corticosteroids, rapamycins and calcineurin inhibitors, appear to play a role. PTHL has been observed in most studies in which patients received calcineurin inhibitor-based regimens, and has been observed with both tacrolimus and cyclosporin. Comparing these calcineurin inhibitors with regard to the relative incidence or severity of PTHL occurring during treatment is difficult because of the use of higher doses of corticosteroids in cyclosporin-based regimens, as compared with tacrolimus-based regimens. However, current expert opinion suggests that the discrepancies in the relative incidence and severity of PTHL are largely accounted for by this difference in corticosteroid dose. At this point in time, evidence for potential differences is scant and inconclusive. Further study is needed, not only to investigate differences in lipid profile, but also of the relative effects of these immunosuppressants on long term graft function as well as on cardiovascular morbidity and mortality. PTHL can be successfully managed with a combination of dietary management, reduction and, if appropriate, withdrawal of corticosteroids, and the administration of lipid-lowering drugs. With this combination of therapeutic options, the threats to long term health posed by PTHL may be effectively addressed.