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Sirolimus monotherapy effectiveness in liver transplant recipients with renal dysfunction due to calcineurin
Fabrizio Di Benedetto1, Stefano Di Sandro, Nicola De Ruvo
1Liver and Multivisceral Transplant Center, University of Modena and Reggio Emilia, Modena, Italy. f.diben@virgilio.it
Introduction:
Among the adverse effects of different calcineurin inhibitors (CIs), nephrotoxicity is the most common (incidence: 18.1% at 13 y from liver transplantation) and depends on a variable degree of tubular-interstitial injury accompanied by focal glomerular sclerosis. A new immunosuppressive drug was introduced in solid organ transplant management, Sirolimus (SRL). It is a nonnephrotoxic immunosuppressor.
Methods:
Twenty-six patients who developed nephrotoxicity owing to CIs, showing an increment of serum creatinine levels (>1.8 mg/dL) were switched to SRL monotherapy, initially at a dosage between 3 and 5 mg/d, and subsequently adapted to achieve trough level between 8 to 10 ng/mL.
Results:
Patients were followed-up for a mean period of 40.3 months (range, 8.4 to 76.7) from liver transplantation. Mean follow-up after switch was 27.5 months (range, 2 to 71.2). Immunosuppression therapy was converted after a mean period of 12.8 months (range, 0.2 to 43.4). Serum creatinine, urea, and estimated glomerular filtration rate were significantly improved.
Discussion:
Patients developing renal dysfunction after liver transplantation may be successfully treated by conversion from CI to SRL. Hypertriglyceridemia and hypercholesterolemia represent the principal side effects from SRL, but are treatable. Furthermore, SRL can significantly improve glucose tolerance.
Insights
Switching calcineurin inhibitors to Sirolimus (SRL) effectively treats nephrotoxicity in liver transplant patients. This immunosuppressive therapy improves kidney function, though managing side effects like hypertriglyceridemia is necessary.
Area of Science:
- Nephrology
- Immunosuppression
- Transplantation Medicine
Background:
- Calcineurin inhibitors (CIs) commonly cause nephrotoxicity in liver transplant recipients, leading to tubular-interstitial injury and glomerular sclerosis.
- Sirolimus (SRL) is a nonnephrotoxic immunosuppressant introduced for solid organ transplant management.
Purpose of the Study:
- To evaluate the efficacy of switching from calcineurin inhibitors (CIs) to Sirolimus (SRL) monotherapy in liver transplant patients experiencing nephrotoxicity.
Main Methods:
- Twenty-six patients with CI-induced nephrotoxicity (serum creatinine >1.8 mg/dL) were switched to SRL monotherapy.
- SRL dosage was initiated between 3-5 mg/d and adjusted to achieve trough levels of 8-10 ng/mL.
Main Results:
- Patients were followed for a mean of 40.3 months post-transplantation and 27.5 months after the switch.
- Significant improvements were observed in serum creatinine, urea levels, and estimated glomerular filtration rate (eGFR) after conversion to SRL.
Conclusions:
- Conversion from CIs to SRL is a successful strategy for managing renal dysfunction in liver transplant recipients.
- While hypertriglyceridemia and hypercholesterolemia are potential side effects of SRL, they are manageable, and SRL may improve glucose tolerance.
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