Late conversion to mammalian target of rapamycin inhibitor/proliferation signal inhibitors in kidney transplant patients: clinical experience in the last 5 years

Introduction: Treatment with proliferation signal inhibitors (PSIs; sirolimus/everolimus) is a therapeutic option for renal transplant recipients, especially those who develop chronic graft nephropathy (CGN) or a neoplasm. We sought to analyze the efficacy and safety of conversion to PSIs.

Material and methods: We undertook a retrospective study of 77 patients converted between January 2005 and October 2009 to PSIs: 53 sirolimus and 24 everolimus. The causes for conversion were 63% tumors, 30% for chronic graft nephropathy (CGN), and 7% for other reasons. Mean time from transplant to conversion was 8 years. Patients were followed for a mean of 18 months (range, 1-61).

Results: A significant 14% improvement in renal function was observed at 1 year after conversion: baseline Modification of Diet in Renal Disease (MDRD) 45±20 versus 51±20.1 mL/min/1.73 m2 (P=.03). The benefit was greater among patients converted for CGN: baseline MDRD 31.5±8.8 versus 40.9±13.1 mL/min/1.73 m2 (P=.02), a 30% increase. The side effects experienced by 40% of patients included: 12% diarrhea, 15% edema, 20% buccal aphthae, 10% pneumonitis, and 20% skin alterations. PSIs were withdrawn in 25% of patients: 13% for side effects, 2.5% for patient death, and 3.8% for graft loss. We observed increases in serum lipids and proteinuria with a mild decrease in hemoglobin.

Conclusion: Conversion to PSIs is a safe, useful therapeutic option for carefully selected patients, when renal function has not undergone marked deterioration and there is no proteinuria. Although side effects are common, most are mild; withdrawal of PSIs was necessary in a relatively low percentage of cases.