Sirolimus monotherapy effectiveness in liver transplant recipients with renal dysfunction due to calcineurin inhibitors.
BACKGROUND
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.


CONCLUSIONS
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.
Di Benedetto
Fabrizio
F
Liver and Multivisceral Transplant Center, University of Modena and Reggio Emilia, Modena, Italy. f.diben@virgilio.it
Di Sandro
Stefano
S
De Ruvo
Nicola
N
Spaggiari
Mario
M
Montalti
Roberto
R
Ballarin
Roberto
R
Cappelli
Gianni
G
Gerunda
Giorgio E
GE
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D065095:Calcineurin Inhibitors; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000009:adverse effects; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D006937:Hypercholesterolemia / Q000139:chemically induced; D015228:Hypertriglyceridemia / Q000139:chemically induced; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects*; D007674:Kidney Diseases / Q000139:chemically induced / Q000517:prevention & control; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D020123:Sirolimus / Q000009:adverse effects / Q000627:therapeutic use*; D016559:Tacrolimus / Q000009:adverse effects; D016896:Treatment Outcome
D001786:Blood Glucose; D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003404:Creatinine; D020123:Sirolimus; D016559:Tacrolimus