Sirolimus dosage during and after conversion from calcineurin inhibitor therapy to sirolimus in chronic kidney transplant patients.
Sirolimus (SRL) is an alternative to calcineurin inhibitors (CNI) in kidney transplant patients with chronic allograft dysfunction.


METHODS
33 patients were converted to SRL receiving a single loading dose of 15 mg and initial maintenance dose of 5 mg/day. CNI was reduced by 50% on day 1 and tapered during 4-6 weeks after achieving SRL target (8-12 ng/ml). Concomitant immunosuppressive therapy remained unchanged.


RESULTS
Patient survival was 100% and graft survival was 85% after 1 year. Mean SRL dose decreased from 5 mg/day initially to 2.8 +/- 1.3 mg/day. SRL dose-adjusted trough concentration did not change significantly over time. Dose-adjusted trough concentrations of CNI before conversion and of SRL after 1 year did not correlate. We observed no severe infections, however, one rejection Banff Ia occurred 7 months after conversion associated with subtherapeutic SRL trough concentration. Adverse events were anemia, dyslipidemia, epistaxis, stomatitis, and bronchiolitis obliterans which occurred mainly during the conversion phase.


CONCLUSIONS
Overlapping conversion from CNI to SRL in chronic kidney transplant patients is possible and safe. However, further studies are necessary with shorter overlap and lower SRL loading and initial maintenance dose which might lead to a decrease in the high number of adverse events in the overlap phase.
Diekmann
Fritz
F
Medizinische Klinik mit Schwerpunkt Nephrologie, Charité Campus Mitte, Berlin, Germany. fritz.diekmann@charite.de
Fritsche
Lutz
L
Neumayer
Hans-Hellmut
HH
Budde
Klemens
K
D065095:Calcineurin Inhibitors; D002908:Chronic Disease; D006084:Graft Rejection / Q000188:drug therapy*; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D016030:Kidney Transplantation / Q000401:mortality*; D011446:Prospective Studies; D020123:Sirolimus / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D014184:Transplantation, Homologous
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D020123:Sirolimus