Use of sirolimus and low-dose calcineurin inhibitor in lung transplant recipients with renal impairment: results of a controlled pilot study.
BACKGROUND
Renal failure induced by calcineurin-inhibitor agents is a common complication of lung transplantation. Sirolimus, a macrolide immunosuppressant with a distinct mechanism of action, may prevent renal failure but was found to have a high infectious and toxicity rate in the only relevant study conducted so far. The aim of the present prospective pilot study was to assess the benefit of sirolimus combined with low-dose calcineurin inhibitors in this patient population.


METHODS
Sixteen lung transplant recipients with post-transplantation renal dysfunction were allocated to receive the standard immunosuppression regimen or a combination sirolimus/low-dose calcineurin-inhibitor regimen. Target trough levels of sirolimus were 4 to 8 ng/mL. Tacrolimus was tapered down to target trough levels of 4 to 8 ng/mL and cyclosporine to 80 to 120 ng/mL. Duration of follow-up was 18 months.


RESULTS
At the end of follow-up, the sirolimus group showed a significant improvement in creatinine clearance (42.6 mL/min vs. 32.5 mL/min, P= 0.05), whereas the control group showed a significant reduction (32.3 mL/min vs. 40.3 mL/min, P= 0.02). The difference between the groups was statistically significant (P < 0.0001). Acute rejection episodes occurred in 2 patients in the sirolimus group and 1 patient in the control group (P= NS). Pneumonia developed in 6 study patients and 4 controls; all responded to antibiotics.


CONCLUSIONS
Sirolimus combined with low-dose calcineurin inhibitors appears to be a safe and effective alternative immunosuppressive therapy to sirolimus alone in lung transplant recipients with renal failure. Graft function is preserved, and infection and drug toxicity rates are low.
Shitrit
David
D
Pulmonary Institute, Rabin Medical Center, Beilinson Campus, Petah Tiqwa, Israel.
Rahamimov
Ruth
R
Gidon
Sahar
S
Bakal
Ilana
I
Bargil-Shitrit
Ariella
A
Milton
Saute
S
Kramer
Mordechai R
MR
D000368:Aged; D003404:Creatinine / Q000378:metabolism; D004359:Drug Therapy, Combination; D004646:Emphysema / Q000601:surgery; D005260:Female; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007674:Kidney Diseases / Q000276:immunology*; D016040:Lung Transplantation / Q000009:adverse effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011183:Postoperative Complications / Q000276:immunology*; D020123:Sirolimus / Q000627:therapeutic use*
D007166:Immunosuppressive Agents; D003404:Creatinine; D020123:Sirolimus