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Published on: November 8, 2015
Immunosuppressive switch to sirolimus in renal dysfunction after liver transplantation
F Di Benedetto1, S Di Sandro, N De Ruvo
1Liver and Multivisceral Transplant Center, University of Modena and Reggio Emilia, Modena, Italy. f.diben@virgilio.it
Objective:
Nephrotoxicity is a serious adverse effect after liver transplantation often related to calcineurin inhibitors (CNI) with a incidence of 18.1% at 5 years. Sirolimus (SRL) is a new immunosuppressive drug that was introduced into solid organ transplant management in 1999. Herein we have performed a retrospective review of patients who developed renal insufficiency owing to CNI therapy after orthotopic liver transplantation (OLT).
Materials And Methods:
Thirty-one patients were switched to SRL monotherapy because of nephrotoxicity as evidenced by serum creatinine levels (SCr) > 1.8 mg/dL and estimated glomerular filtration rates (eGFR) < 45 mL/min/1.73 m(2). The dosage was adjusted to achieve trough levels between 8 and 10 ng/mL.
Results:
The patients were followed for a mean of 52 months (range 2-88 months) after OLT. Mean follow-up after the switch was 27.5 months (range, 2-71.2 months). Immunosuppression was switched after a mean of 35.2 months (range, 0.2-43.4 months). Renal function was significantly improved, as shown by the improved SCr, urea, and eGFR after the switch.
Conclusions:
CNIs may be associated with significant nephrotoxicity and chronic kidney damage. Patients who develop renal dysfunction after OLT may be successfully treated by an early switch from CNIs to SRL, stopping the progression toward chronic renal damage and preserving allograft survival.
Insights
Switching from calcineurin inhibitors (CNIs) to sirolimus (SRL) improved kidney function in liver transplant patients experiencing nephrotoxicity. This change helped halt chronic kidney damage and preserve graft survival.
Area of Science:
- Nephrology
- Transplant Immunology
- Pharmacology
Background:
- Calcineurin inhibitors (CNIs) are associated with significant nephrotoxicity in liver transplant recipients, occurring in 18.1% of patients within 5 years.
- Sirolimus (SRL) is an alternative immunosuppressant introduced in 1999 for solid organ transplantation.
Purpose of the Study:
- To evaluate the efficacy of switching immunosuppression from CNIs to SRL monotherapy in patients with CNI-induced nephrotoxicity after orthotopic liver transplantation (OLT).
Main Methods:
- Retrospective review of 31 patients with CNI-induced nephrotoxicity (serum creatinine > 1.8 mg/dL, eGFR < 45 mL/min/1.73 m²).
- Patients were switched to SRL monotherapy, with dosages adjusted for trough levels of 8-10 ng/mL.
- Mean follow-up was 52 months post-OLT and 27.5 months post-switch.
Main Results:
- Renal function significantly improved after switching to SRL, indicated by better serum creatinine, urea levels, and estimated glomerular filtration rates (eGFR).
- The switch occurred at a mean of 35.2 months after OLT.
Conclusions:
- CNI-induced nephrotoxicity can lead to chronic kidney damage in liver transplant recipients.
- Early conversion from CNIs to SRL can successfully treat renal dysfunction, prevent further kidney damage, and support long-term allograft survival.
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