Conversion to Sirolimus in Renal Transplant Patients With Tumors (original) (raw)
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Conversion from calcineurin inhibitors to sirolimus in renal transplant patients
2008
Sirolimus is a potent immunosuppressive drug that prevents acute rejection episodes and is a possible alternative to calcineurin inhibitors. A retrospective study was performed to evaluate the efficacy and safety of conversion from a calcineurin inhibitor to sirolimus during maintenance immunosuppressive therapy in selected renal transplant recipients. The calcineurin inhibitor (cyclosporine – 82%, tacrolimus – 18%) was switched to sirolimus either progressively or abruptly, in 17 deceased renal transplant recipients at 0.5 to 50 (median – 8.6) months post-transplant. In 14 out of 17 patients graft dysfunction (plasma creatinine ≥1.8 mg/dl) was the main reason for conversion. In 10 patients graft biopsy was performed and confirmed acute CNI nephrotoxicity (n=5), chronic nephropathy (n=4) and thrombotic microangiopathy (n=1) and 4 patients had clinical chronic graft dysfunction. The other 3 patients were converted due to neoplasia: squamous cell carcinoma, renal cell cancer and polyc...
Transplantation Proceedings, 2009
While conversion of stable renal transplant recipients (RTR) from calcineurin inhibitors (CNI) to sirolimus (SRL) is safe and effective, it is still under investigation for recent, high-risk cases. We studied the long-term effects of conversion of high-risk subjects maintained on a CNI, mycophenolate mofetil, plus steroid regimen to SRL, mycophenolate mofetil, plus steroid on graft and patient outcomes. We retrospectively reviewed the first 100 RTR converted to SRL treatment over approximately 5 years. The main indications for conversion were biopsy-proven acute rejection (BPAR), CNI toxicity, CNI elimination, and acute-tubular necrosis (ATN). Exclusion criteria were limited to bone marrow suppression. The overall mean Ϯ SD age was 38.5 Ϯ 15.6 years, including pediatric and geriatric age groups. Mean Ϯ SD body mass index (BMI) was 28.99 Ϯ 8.0 and 40% had a BMI Ͼ 30. There were 40% RTR from deceased donors and 60% showed 4 to 6 HLA mismatches. Preconversion total BPAR and steroid-resistant rejection incidences were 35% and 14%, respectively. Mean Ϯ SD time to start of SRL was 11.9 Ϯ 22.8 months posttransplantation. Proteinuria Ͼ 2 g/d, leukopenia, and hyperlipidemia increased significantly after conversion (P ϭ .001, P ϭ .0003, and P ϭ .0001, respectively). Patient and graft survivals were 95% and 90%, respectively. There was significant improvement in graft function postconversion (P Ͻ .0001). There was a high incidence of side effects and cases of SRL discontinuation. Multivariate analysis demonstrated the influence of bone marrow suppression, obesity, hyperlipidemia, nutritional status, proteinuria, and graft function on graft and patient outcomes. We concluded that conversion from CNI to SRL was effective among high-risk RTR, but with a high incidence of adverse events during long-term follow-up.
Conversion to Sirolimus in Posttransplant Renal Neoplasms
Transplantation Proceedings, 2007
Background. Calcineurin inhibitors (CNIs) have been associated with the development of posttransplant malignancies, especially lymphoma and solid organ tumors. Sirolimus (SRL) has been shown to inhibit the growth of tumor cell lines in vitro and in vivo and has proven effective in clinical practice for the treatment of Kaposi's sarcoma. Organ transplant patients treated with CNIs who develop a tumor may thus benefit from conversion to SRL. Patients and methods. From December 2001 to May 2006, 25 patients who developed a tumor were converted from a CNI-based immunosuppressive regimen to SRL. We analyzed the evolution of the tumor, renal function, and the adverse effects resulting from the change of immunosuppression.
Conversion to Sirolimus in Renal Transplant Recipients: A Single-Center Experience
Artificial Organs, 2010
Maintenance immunosuppression with calcineurin inhibitors (CNI) following renal transplantation is associated with nephrotoxicity and accelerated graft loss. Sirolimus (SRL) is a nonnephrotoxic immunosuppressive agent. We retrospectively analyzed our experience with kidney transplant recipients who were converted from CNI to SRL. A total of 58 renal transplant recipients were converted from CNI to SRL. SRL was started at a dose of 0.075 mg/kg and, at the same time, CNI dose was reduced by 50% daily for 3 days. SRL trough levels were targeted between 8 and 12 ng/mL. When target trough levels were achieved, CNI was withdrawn. The main indications for switching were posttransplant malignancies (n = 32) and chronic allograft nephropathy (CAN) (n = 10). The mean time from transplantation to conversion was 84 Ϯ 71 months. Mean serum creatinine level was 1.63 Ϯ 0.52 mg/dL before conversion. Serum creatinine levels at the 1, 3, 6 months, and 1, 2, 3 years after conversion were 1.64 Ϯ 0.58 mg/dL (P = 0.67), 1.52 Ϯ 0.53 mg/dL (P =
Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation, 2012
This retrospective single-center study evaluated long-term renal function after conversion from calcineurin inhibitors to sirolimus-based immunosuppression in kidney transplant recipients. From 2001 to 2009, one hundred fifty kidney transplant recipients were converted from calcineurin inhibitors to sirolimus at least 3 months after transplant. After a mean follow-up of 171 weeks, 56.7% of converted patients remained on sirolimus. The 5-year survival rate of the patients (including intent-to-treat) and grafts was 85.5% and 83.6%. Patients on sirolimus showed significant improvement in renal function with a creatinine clearance of 50.9 ± 20.7 and 52.9 ± 20.8 mL/minute at month 0 and month 24. Independent predictive factors associated with a stable estimated glomerular filtration rate at the last follow-up of sirolimus patients were (1) having a living donor, (2) absence of anti-HLA alloantibodies at month 0, and (3) cyclosporine versus tacrolimus used before conversion. Adverse effec...
Electronic Journal of General Medicine, 2016
Background/Aim: We report a prospective, open-label, randomized study to evaluate the safety and efficacy of converting patients with stable renal function from Tacrolimus (Tac)-based regimen to a Sirolimus (SRL)-based regimen after kidney transplantation. Methods: Fifty eight low risk renal allograft recipients who were eligible to the study, 6 months posttransplant and receiving Tac, were randomly assigned to continue Tac (n=29) or convert to SRL (n=29). We evaluated the 3-year outcomes including patient and graft survival, graft function and safety profile. Results: 3-year patient and graft survival in SRL and Tac groups was 93.1% vs. 100% (P=0.04), and 89.7% vs. 100% (P=0.04), respectively. However, the SRL group had significantly better renal function, from the second year post-transplant until the last follow-up. Four (13.8%) patients in the SRL group and 3 (10.3%) in the Tac group (P=0.5) developed biopsy proven acute rejection. Mean urinary protein excretion increased significantly after SRL conversion. Diastolic blood pressure was significantly lower in patients who eliminated tacrolimus (80.4 vs. 75.6 mmHg) (P = 0.03). Mean hemoglobin concentrations decreased after SRL conversion and remained significantly lower from 12 months to 36 months (P=0.01). The mean serum cholesterol and triglyceride levels increased significantly in the SRL group, (P < 0.05). Conclusions: our experience demonstrates that conversion to sirolimus from calcineurin inhibitors (CNI)-based therapy may result in better renal function and blood pressure control in renal transplant recipients without an increased risk of acute rejection. However, these benefits have not resulted in a growing advantage in graft or patient survival.
Nephrology Dialysis Transplantation, 2005
Background. Switching from calcineurin inhibitors (CNIs) to sirolimus might improve renal function in chronic renal transplant patients. Methods. In a prospective study, we assessed longterm efficacy and safety parameters in 43 renal transplant recipients who were switched from a CNI (cyclosporin A, 65%; and tacrolimus, 35%) to sirolimus for either chronic allograft dysfunction (n ¼ 38) or recurrent cutaneous cancers (n ¼ 5). A kidney biopsy was done in 79% of patients prior to conversion, and showed either chronic allograft nephropathy (n ¼ 26) or CNI nephrotoxicity (n ¼ 7). Conversion was either abrupt or progressive, with CNI withdrawal over 3 weeks. All patients also received steroids with or without mycophenolate mofetil or azathioprin. Patient data were recorded at baseline (D0), at 1 (D30) and 6 months (D180), and at 1, 1.5 and 2 years post-conversion. Results. After a mean post-conversion follow-up of 27±1.5 months, 58% of the patients were still on sirolimus. The survival of intent to treat patients and grafts was 95.3 and 93%, respectively. Overall, there was significant improvement in renal function, creatinine clearance increasing from 49.4±14.9 to 53± 16.3 ml/min at D30 (P ¼ 0.01), and to 54.7±20 ml/min at D180 (P ¼ 0.01). Thereafter, creatinine clearance was not different from baseline, i.e. 54.7±21.7, 52.8±20 and 51.7±20.3 ml/min at years 1, 1.5 and 2, respectively. We divided the patients into two groups: responders (n ¼ 29), those with an increase in creatinine clearance at 6 months post-conversion compared with D0, and non-responders (n ¼ 14), those with a decrease in creatinine clearance at 6 months postconversion compared with D0. In univariate analysis, factors predictive of response included proteinuria at D0 and the magnitudes of the differences between D30 and D0 for serum creatinine and lactate dehydrogenase. The conversion was associated with (i) significant decreases in serum calcium, phosphorus and uric acid, and in haemoglobin levels; (ii) significant increases in serum alkaline phosphatase, total cholesterol, parathyroid hormone, and the number of patients on statin and recombinant erythropoietin therapies; and (iii) the appearance of de novo proteinuria of >1 g/day in 28% of patients (P<0.0009), which was >2 g/day in 12% of the entire cohort. Kidney biopsies in 17 patients 2 years after conversion showed the same Banff scores as observed at baseline. We identified three independent predictive factors for a renal response to the switch: absence of proteinuria, presence of antihypertensive therapy at D0 and serum lactate dehydrogenase level at D30. Conclusion. Conversion from CNIs to sirolimus in renal transplant patients with chronic allograft nephropathy was associated with improved renal function; however, 33% of the patients developed overt proteinuria.
Long-Term Outcomes Following Sirolimus Conversion after Renal Transplantation
Immunological Investigations, 2014
Long-term outcomes following renal transplantation remain limited due to chronic progressive injury partly as a result of calcineurin inhibitor (CNI) toxicity. Thus, patients have been converted to non-CNI immunosuppressives despite the lack of evidence of long-term benefits from CNI free therapy. We now report our 10-year experience converting patients with well functioning transplants from CNI to sirolimus. We retrospectively analyzed outcomes of patients receiving continuous CNI based therapy (CNI, n = 309) or who were switched to sirolimus within the first year of posttransplantation (CONV, n = 54). The groups were similar for most recipient, graft and donor characteristics, however, diabetes was more common in the CNI group and statin use was more frequent in the CONV group. The average time to conversion was 7.2 months and the creatinine level at the time of switching was 1.4 mg/dl. Ten year graft and patient survival rates were equivalent in both groups. There were no differences in the causes of death or graft loss in both groups. Renal function was available for 5 years posttransplant and was no different between groups. Thus, there is no evidence that routinely switching patients with well functioning renal allografts to sirolimus from CNI based immunosuppression provides long-term benefit.
Sirolimus in renal transplant recipients with malignancies in Germany
Clinical Kidney Journal, 2021
Background Renal transplant recipients have an increased cancer risk. The mammalian target of rapamycin inhibitor sirolimus (SRL) has immunosuppressive and antitumour activities but knowledge about its use in recipients with cancer is limited. Methods We retrospectively analysed 726 renal allograft recipients converted to SRL from 10 German transplant centres. Patient and graft survival were analysed depending on malignancy status prior to conversion and tumour entity. Results Malignancy before conversion to SRL was reported in 230 patients, with 137 patients having skin cancers and 101 having solid cancers. Cancer occurred 4.6 ± 9.4 (median 3.0) years after transplantation. Basal cell carcinoma, squamous cell carcinoma and Bowen’s disease were the most prevalent skin cancers, while carcinomas of the kidney, colon and breast were the most prevalent solid cancers before conversion. Patients with prior malignancy were older and had better renal function at conversion compared with pat...