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Sirolimus in chronic allograft nephropathy
Abstract:
Chronic allograft nephropathy (CAN) is the most common cause of late renal transplant loss. Calcineurin inhibitor (CNI) nephrotoxicity is known to contribute to CAN. A sirolimus-based regimen way allow for early CNI reduction or elimination. The aim of the present study was to determine the efficacy and safety of a sirolimus-based regimen for CAN. From December 2001 to August 2003, kidney transplant (KTx) recipients with CAN were enrolled for treatment with sirolimus. Among 32 studied patients, 24 (75%) underwent graft biopsy before the initiation of sirolimus. Baseline maintenance immunosuppression consisted of cyclosporine/tacrolimus and prednisone with or without mycophenolate mofetil. The follow-up duration on sirolimus therapy was 8.5 +/- 5.9 months (range: 1 to 22 months). The average dosage of sirolimus was 1.8 +/- 0.5 mg/d at the end of follow-up. The mean trough level of sirolimus was 5.1 +/- 2.1 ng/mL. Sirolimus was effective in 16 (50%) patients while 3 (9.4%) patients improved (serum creatinine [Cr] decrease > 10%) and 13 (40.6%) maintained stable (change of serum Cr within 10%). Sirolimus was effective in 5 (35.7%) patients whose serum Cr was over 3.0 mg/dL but failed to rescue all four patients whose serum Cr was over 4.0 mg/dL. Eleven (68.8%) of 16 responders showed a reduction (29.8% +/- 13.8%) in CNI dosage. The most common adverse events were hyperlipidemia (37.5%), anemia (25%), and diarrhea (21.8%). Twelve patients discontinued sirolimus due to graft failure (4), severe infection (3), stroke related mortality (1), anemia (2), diarrhea (1), and edema (1). In conclusion, sirolimus is effective in 50% of KTx recipients with CAN, especially when the serum Cr is less than 3.0 mg/dL. However, the increased incidence of infection, diarrhea, and hyperlipidemia are of major concern.
Insights
Sirolimus effectively treated chronic allograft nephropathy (CAN) in 50% of kidney transplant recipients, particularly those with serum creatinine below 3.0 mg/dL. Adverse events like infection and hyperlipidemia require careful monitoring.
Area of Science:
- Nephrology
- Immunology
- Pharmacology
Background:
- Chronic allograft nephropathy (CAN) is a primary cause of late kidney transplant loss.
- Calcineurin inhibitor (CNI) nephrotoxicity is a significant contributor to CAN development.
- Sirolimus-based immunosuppression may allow for reduced or eliminated CNI use.
Purpose of the Study:
- To evaluate the efficacy and safety of sirolimus in kidney transplant recipients diagnosed with CAN.
- To assess the impact of sirolimus on graft function and patient outcomes in the context of CAN.
Main Methods:
- A prospective study involving 32 kidney transplant recipients with CAN treated with sirolimus.
- Patients received sirolimus alongside baseline immunosuppression (CNI, prednisone, mycophenolate mofetil).
- Graft biopsies were performed on 75% of patients prior to sirolimus initiation; follow-up averaged 8.5 months.
Main Results:
- Sirolimus demonstrated effectiveness in 50% of patients, with 9.4% showing improvement and 40.6% maintaining stable renal function.
- Efficacy was more pronounced in patients with serum creatinine < 3.0 mg/dL; effectiveness was limited in those with serum creatinine > 4.0 mg/dL.
- Common adverse events included hyperlipidemia (37.5%), anemia (25%), and diarrhea (21.8%); 12 patients discontinued therapy due to various complications.
Conclusions:
- Sirolimus is an effective treatment option for approximately 50% of kidney transplant recipients with CAN, particularly when serum creatinine is below 3.0 mg/dL.
- The use of sirolimus can lead to a reduction in CNI dosage in responders.
- Increased incidence of adverse events such as infection, diarrhea, and hyperlipidemia necessitates careful patient management and monitoring.
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