Conversion to sirolimus in solid organ transplantation: a single-center experience.
BACKGROUND
Calcineurin inhibitors are associated with adverse events, including nephrotoxicity and diabetes that might reduce the benefits of long-term graft survival. We report our experience in converting kidney (K), kidney-pancreas (KP), pancreas (P), and (L) recipients from a calcineurin inhibitor/mycophenolate mofetil (MMF)/prednisone dose-induced nephrotoxicity (K = 9, KP = 5, P = 1, L = 5), hemolytic uremic syndrome (HUS) (K = 7, KP = 5), chronic allograft nephropathy (K = 12, L = 1), and glucose intolerance (K = 9, KP = 6, P = 2, L = 2).


METHODS
The conversion protocol consisted of an abrupt discontinuation of the calcineurin inhibitor with sirolimus (8-12 mg, PO loading dose) initiated 24-72 hours after stopping the calcineurin inhibitor. Sirolimus was titrated to target trough levels of 12-16 ng/mL. Daclizumab 2 mg/kg IV was given to all KP and P recipients on days 0 and 14 postconversion.


RESULTS
Resolution of HUS occurred in 12 of 12 patients (100%) with a drop in serum creatinine from 3.3 +/- 1.5 to 1.8 +/- 0.9 mg/dL (P =.04). Sirolimus conversion due to nephrotoxicity, HUS, and chronic allograft nephropathy improved serum creatinine from 2.9 +/- 1.4 to 2.2 +/- 0.9 mg/dL (P =.01). Eleven of 19 patients (58%) resolved glucose intolerance. Two patients suffered rejection due to noncompliance. Increases in cholesterol (208 +/- 70 to 243 +/- 77 mg/dL, P <.05) and triglycerides (232 +/- 145 to 265 +/- 148 mg/dL, P = NS), and minimal reduction in platelet values (243 +/- 85 to 237 +/- 85, P = NS) occurred.


CONCLUSIONS
These data suggest that a calcineurin inhibitor-free immunosuppressive regimen with sirolimus, mycophenolate mofetil, and steroids preserves graft function in patients with clinical indications warranting calcineurin inhibitor discontinuation.
Nephrology Division, University of Tennessee, Memphis, TN, USA. megidi@utmem.edu
M F
MF
Egidi
P A
PA
Cowan
A
A
Naseer
A O
AO
Gaber
D000328:Adult; D065095:Calcineurin Inhibitors; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D008297:Male; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives*; D016035:Pancreas Transplantation / Q000276:immunology* / Q000473:pathology; D011183:Postoperative Complications / Q000139:chemically induced; D011241:Prednisone / Q000009:adverse effects; D044469:Racial Groups; D012189:Retrospective Studies; D020123:Sirolimus / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013997:Time Factors
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D011241:Prednisone; D020123:Sirolimus