Results of 4-Year Analysis of Conversion from Calcineurin Inhibitors to mTOR Inhibitors in Renal Transplant Patients: Single-Center Experience

Abstract

In this retrospective study, 83 patients were accepted. Mammalian target of rapamycin (mTOR) group consisting of 37 patients were converted from calcineurin inhibitors (CNI), and the control group included 46 patients (initially CNIreceiving patients). As a control-match of each mTOR inhibitor patient, the succeeding patient with transplantation who continued CNI therapy was chosen. All patients received CNI, MMF, and prednisolone as an immunosuppressive therapy initially. In comparison of two groups, there was no significant difference between sex, donor organ source, donor organ ischemia time, or mismatches. However, mean age between groups was significantly different (mTOR group: 48.3 ± 12, CNI group: 38.6 ± 11, p < 0.001). Decision of conversion to mTOR inhibitors in 30 patients was made by biopsy. The reasons for conversion were determined as CNI nephrotoxicity in 15 patients, chronic allograft nephropathy in 15 patients, malignancy in 6 patients, and renal artery stenosis in 1 patient. Basal glomerular filtration rates (GFRs) were markedly lower in mTOR group than in CNI group (38.8 mL/min vs. 72.7 mL/min). At the end of 48-month follow-ups, GFR increased from 38 mL/min to 54 mL/min in mTOR group; however, it decreased to 53 mL/min from 72 mL/min in CNI group. There was no difference left between the two groups in GFR after 4-year followup. Hyperlipidemia was higher in mTOR group. Acute rejection rates were similar. Cytomegalovirus (CMV) disease was more prevalent in CNI group. Graft failure developed due to secondary reasons, causing mortality in both groups. We suggest that conversion to mTOR inhibitors maintains and improves graft functions well.

Safety considerations of mammalian target of rapamycin inhibitors in tuberous sclerosis complex and renal transplantation

“…Clear evidence shows that mTOR inhibitors are beneficial in the setting of preexisting renal injury if their use allows dose reduction or withdrawal of another nephrotoxic agent . For example, rapalog use improves glomerular filtration rate in renal transplant patients with chronic allograft nephropathy mediated by CNI therapy, who are converted from CNI to mTOR inhibition . Whether this advantage of mTOR inhibitors will mitigate renal injury in TSC patients remains to be seen: although TSC kidneys generally have less nephrotoxic exposure than allografts, they may have vascular or proliferative lesions that could respond favorably to pharmacologic mTOR inhibition.…”