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Conversion from calcineurin inhibitors to sirolimus in patients with chronic renal allograft dysfunction
M Fischereder1, C Graeb, B Krüger
1University of Regensburg, München, Germany.
Background:
Chronic renal transplant dysfunction in part may be due to the nephrotoxic effects of calcineurin inhibitors, which are still the mainstay of immunosuppressive therapy. Sirolimus, a new immunosuppressive compound devoid of significant nephrotoxicity, might therefore exhibit beneficial effects when used in renal transplant recipients with graft dysfunction.
Methods:
Twelve renal transplant recipients included in this study had all been receiving calcineurin inhibitors for more than 12 months, and were free of rejection for more than 12 months. However, they demonstrated moderate renal dysfunction with serum creatinine values ranging from 1.8 to 4.0 mg/dL (164 to 351 micromol/L). After reaching a sirolimus level of 10 to 20 ng/mL, calcineurin inhibitor therapy was withheld.
Results:
One month after initiation of sirolimus therapy, all patients were off calcineurin inhibitors. The average daily sirolimus dosage was 5.8+/-3.4 mg. No acute rejection episode and no graft failure was observed. No patient required hemodialysis or admission to the hospital. Calculated creatinine clearance increased from 63.4+/-9.9 to 69.2+/-9.7 mL/min (P=.0368) and serum bicarbonate increased from 20.8+/-3.17 to 22.5+/-3.7 meq/L (P=.001). Serum cholesterol increased from 180+/-26.5 to 239+/-28.8 mg/dL (4.65+/-0.69 to 6.18+/-0.74 mmol/L, P<.001), triglycerides increased from 155+/-53 to 289+/-123 mg/dL (1.75+/-0.6 to 3.26+/-1.39 mmol/L) and low-density lipoprotein cholesterol increased from 99+/-32 to 131+/-25.1 mg/dL (2.56+/-0.83 to 3.39+/-0.65 mmol/L, P=.01). Arterial blood pressure remained well controlled (126+/-15.6/74+/-8.9 vs 134+/-16.8/83+/-9.7).
Conclusion:
Conversion from calcineurin inhibitor therapy to sirolimus in patients more than 1 year after transplantation with impaired organ function is feasible, safe, and associated with a trend toward improved renal function.
Insights
Switching renal transplant patients with impaired function from calcineurin inhibitors to sirolimus is safe and feasible. This conversion showed a trend toward improved kidney function and avoided rejection episodes.
Area of Science:
- Nephrology
- Immunosuppression
- Transplantation
Background:
- Calcineurin inhibitors (CNIs) are standard immunosuppressants post-renal transplant but can cause nephrotoxicity, leading to chronic graft dysfunction.
- Sirolimus, an immunosuppressive agent, lacks significant nephrotoxicity, suggesting potential benefits for renal transplant recipients with declining kidney function.
Purpose of the Study:
- To evaluate the feasibility, safety, and efficacy of converting renal transplant recipients with moderate graft dysfunction from calcineurin inhibitors to sirolimus.
Main Methods:
- Twelve renal transplant recipients with stable graft dysfunction (serum creatinine 1.8-4.0 mg/dL) on CNI therapy for over a year were switched to sirolimus.
- CNI therapy was withdrawn after achieving target sirolimus levels (10-20 ng/mL).
Main Results:
- All patients successfully transitioned off CNIs within one month without rejection or graft failure.
- Calculated creatinine clearance improved significantly (63.4 to 69.2 mL/min, P=.0368), and serum bicarbonate levels increased (P=.001).
- Lipid profiles showed increases in cholesterol, triglycerides, and LDL, while blood pressure remained controlled.
Conclusions:
- Conversion from CNIs to sirolimus is feasible and safe in renal transplant patients with impaired function over one year post-transplant.
- This switch demonstrates a trend toward improved renal function and is a viable therapeutic option.
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