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Published on: April 12, 2021
Cardiovascular risk profile in patients treated with sirolimus after renal transplantation
1Renal Transplant Unit, Nephrology Department, Hospital 12 de Octubre, 28041 Madrid, Spain. jmorales@h12o.es
Insights
Renal transplant patients face high cardiovascular disease (CVD) risk. Early withdrawal of calcineurin inhibitors (CNIs) like cyclosporine (CsA) improved renal function and graft survival, with manageable lipid increases.
Area of Science:
- Nephrology
- Cardiology
- Immunology
Background:
- Renal transplant recipients have a high predisposition to cardiovascular disease (CVD).
- CVD is the leading cause of death in patients with functioning renal grafts.
- Calcineurin inhibitors (CNIs), such as cyclosporine (CsA), have nephrotoxic effects detrimental to transplant outcomes.
Purpose of the Study:
- To evaluate the benefits of early calcineurin inhibitor (CNI) withdrawal in renal transplant patients.
- To compare CNI-free immunosuppressive therapy with CNI-based regimens regarding cardiovascular risk factors and patient survival.
- To assess the long-term impact of sirolimus-based immunosuppression after CsA withdrawal.
Main Methods:
- A 4-year study involving early withdrawal of cyclosporine (CsA) from a sirolimus-CsA-steroid (SRL-CsA-ST) combination regimen.
- Monitoring of renal function, blood pressure, serum lipids, and graft survival post-CsA withdrawal.
- Management of sirolimus-induced hyperlipidemia with lipid-lowering therapy.
Main Results:
- Significantly improved renal function was observed after CsA withdrawal.
- Lower blood pressure and enhanced graft survival rates were noted in the CNI-withdrawal group.
- Sirolimus-induced increases in serum lipids were generally manageable with appropriate treatment.
Conclusions:
- Early CsA withdrawal from SRL-CsA-ST regimens can improve renal function, blood pressure, and graft survival.
- CNI-free or CNI-sparing strategies warrant further investigation for reducing cardiovascular risk in renal transplant recipients.
- Sirolimus-based immunosuppression offers a viable alternative to CNIs, with manageable side effects.
Abstract:
Renal transplant patients are inherently predisposed to cardiovascular disease (CVD) as a result of prolonged exposure to multiple cardiovascular risk factors. Approximately one half of all late graft losses are due to death with a functioning graft, and CVD is the most frequent cause of death with a functioning graft among these patients. Immunosuppressive therapies associated with a reduced burden of risk for CVD would therefore greatly decrease post-transplantation morbidity and mortality. The nephrotoxic effects observed with the use of calcineurin inhibitors (CNIs), such as cyclosporine (CsA), run counter to the goal of renal transplant therapy. Sirolimus, a more recent immunosuppressive agent with a unique mechanism of action, offers an alternative to CsA. Recent data from a 4-year study investigating early CsA withdrawal from a sirolimus-CsA-steroid (SRL-CsA-ST) combination demonstrated significantly better renal function, lower blood pressure, and improved graft survival after CsA withdrawal. During that trial, the increase in serum lipids induced by sirolimus was generally manageable with lipid-lowering therapy. Further investigation is warranted to evaluate the value of CNI-free therapy compared with CNI-based regimens in reducing cardiovascular risk factors and improving patient and graft survival.
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