Conversion from calcineurin inhibitors to sirolimus in patients with chronic renal allograft dysfunction.
BACKGROUND
Chronic renal transplant dysfunction in part may be due to the nephrotoxic effects of calcineurin inhibitors, which are still the mainstay of immunosuppressive therapy. Sirolimus, a new immunosuppressive compound devoid of significant nephrotoxicity, might therefore exhibit beneficial effects when used in renal transplant recipients with graft dysfunction.


METHODS
Twelve renal transplant recipients included in this study had all been receiving calcineurin inhibitors for more than 12 months, and were free of rejection for more than 12 months. However, they demonstrated moderate renal dysfunction with serum creatinine values ranging from 1.8 to 4.0 mg/dL (164 to 351 micromol/L). After reaching a sirolimus level of 10 to 20 ng/mL, calcineurin inhibitor therapy was withheld.


RESULTS
One month after initiation of sirolimus therapy, all patients were off calcineurin inhibitors. The average daily sirolimus dosage was 5.8+/-3.4 mg. No acute rejection episode and no graft failure was observed. No patient required hemodialysis or admission to the hospital. Calculated creatinine clearance increased from 63.4+/-9.9 to 69.2+/-9.7 mL/min (P=.0368) and serum bicarbonate increased from 20.8+/-3.17 to 22.5+/-3.7 meq/L (P=.001). Serum cholesterol increased from 180+/-26.5 to 239+/-28.8 mg/dL (4.65+/-0.69 to 6.18+/-0.74 mmol/L, P<.001), triglycerides increased from 155+/-53 to 289+/-123 mg/dL (1.75+/-0.6 to 3.26+/-1.39 mmol/L) and low-density lipoprotein cholesterol increased from 99+/-32 to 131+/-25.1 mg/dL (2.56+/-0.83 to 3.39+/-0.65 mmol/L, P=.01). Arterial blood pressure remained well controlled (126+/-15.6/74+/-8.9 vs 134+/-16.8/83+/-9.7).


CONCLUSIONS
Conversion from calcineurin inhibitor therapy to sirolimus in patients more than 1 year after transplantation with impaired organ function is feasible, safe, and associated with a trend toward improved renal function.
Fischereder
M
M
University of Regensburg, München, Germany.
Graeb
C
C
Krüger
B
B
Kammerl
M C
MC
Zülke
C
C
Jauch
K W
KW
Krämer
B K
BK
D000328:Adult; D000368:Aged; D001379:Azathioprine / Q000009:adverse effects; D001806:Blood Urea Nitrogen; D065095:Calcineurin Inhibitors; D003404:Creatinine / Q000378:metabolism; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives; D020123:Sirolimus / Q000627:therapeutic use*; D014184:Transplantation, Homologous
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D003404:Creatinine; D009173:Mycophenolic Acid; D001379:Azathioprine; D020123:Sirolimus