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Sirolimus experience in heart transplantation
A Aranda-Dios1, E Lage, J M Sobrino
1Department of Cardiology, University Hospital Virgen del Rocío, Seville, Spain. arandios@hotmail.com
Introduction:
Sirolimus is a potent, nonnephrotoxic immunosuppressant with antiproliferative activity in nonimmune cells. Recent data support the conversion in late renal failure secondary to calcineurin inhibitors (CNIs), with limited experience in de novo regimens in patients with predictive factors of postoperative renal impairment.
Objective:
We evaluated our experience of sirolimus-based immunosuppression administered to 25 heart transplant recipients.
Methods:
A retrospective analysis of 25 heart transplant recipients who received sirolimus included 17 conversions due to late CNI-related chronic renal dysfunction, six patients with a de novo regimen, and two patients who developed posttransplant pulmonary neoplasms. The conversion from CNI to sirolimus was started with 2 mg, with an average time after transplantation of 78 +/- 43 months and a mean baseline serum creatinine level of 2.1 +/- 0.45 mg/dL. The mean clinical follow-up was 17 +/- 9 months postconversion, and included echocardiography and laboratory studies. In the de novo group successive endomyocardial biopsies were performed during the first semester.
Results:
Serum creatinine fell from 2.1 +/- 0.45 mg/dL to 1.8 +/- 0.51 mg/dL (P = .012). Mean sirolimus levels were 15 +/- 9 ng/mL (doses 2.2 +/- 0.4 mg). This improvement continued until 3 months (creatinine 1.5 +/- 0.35 P < .01)/sirolimus levels 11.7 +/- 5 ng/mL [1.9 +/- 0.7 mg]), with maintenance at 6 months (1.58 +/- 0.3 mg/dL/14 +/- 4 ng/mL [1.85 +/- 0.7 mg]) and 1-year postconversion (1.53 +/- 0.39 mg/dL; P = .019/10.7 +/- 2.5 ng/mL [1.5 +/- 0.7 mg]). De novo, after a mean follow-up of 13 months (range 3 to 35), sirolimus appeared to increase the incidence of a moderate histological grade of rejection without hemodynamic compromise. Side effects were common (63%), including peripheral edema, skin eruptions, and pericardial effusion. Only one patient discontinued treatment, due to intestinal intolerance. Four patients died during follow-up: two because of lung neoplasms and two because of progressive graft vessel disease.
Conclusion:
Sirolimus improved late CNI-related chronic renal dysfunction. Kidney function was preserved using a de novo CNI-free immunosuppressive regimen for recent cardiac transplant recipients.
Insights
Sirolimus improved kidney function in heart transplant patients with calcineurin inhibitor-related renal dysfunction. A de novo sirolimus regimen preserved kidney function but showed increased rejection rates.
Area of Science:
- Nephrology
- Immunology
- Cardiology
Background:
- Sirolimus is an immunosuppressant with antiproliferative properties.
- It is nonnephrotoxic and shows potential for managing renal dysfunction post-transplant.
- Limited data exist on de novo sirolimus regimens in high-risk patients.
Purpose of the Study:
- To evaluate sirolimus-based immunosuppression in heart transplant recipients.
- To assess sirolimus for converting from calcineurin inhibitors (CNIs) in patients with renal dysfunction.
- To evaluate de novo sirolimus regimens in select heart transplant patients.
Main Methods:
- Retrospective analysis of 25 heart transplant recipients.
- 17 patients converted from CNIs to sirolimus for renal dysfunction.
- 6 patients received a de novo sirolimus regimen; 2 received it due to posttransplant neoplasms.
Main Results:
- Serum creatinine levels significantly decreased post-conversion from CNIs to sirolimus.
- Kidney function improved and was maintained up to 1 year post-conversion.
- The de novo sirolimus group showed a higher incidence of moderate rejection; side effects were common.
Conclusions:
- Sirolimus effectively improved late CNI-related chronic renal dysfunction in heart transplant recipients.
- A de novo CNI-free regimen with sirolimus preserved kidney function in recent heart transplant recipients.
- Sirolimus use requires careful monitoring due to potential side effects and rejection rates.
