Prospective observational study of sirolimus as primary immunosuppression after renal transplantation.

BACKGROUND.: Sirolimus (SRL) is an important component of clinical immunosuppression in renal transplantation, but few international studies have examined how this agent is used in routine practice. METHODS.: Within a large prospective pharmacoepidemiological study, 718 de novo renal graft recipients treated with SRL in 65 centers in 10 countries were monitored for up to 5 years posttransplant to compare the principal outcomes and adverse effects by treatment regimen. RESULTS.: Principal treatment regimens were SRL without a calcineurin inhibitor (33%), SRL+cyclosporine A (CsA) (33%), and SRL+tacrolimus (TAC) (34%); 18% of subjects discontinued SRL, 124/718 (17%) developed biopsy-confirmed acute rejection (BCAR), 64/718 (9%) lost their graft, and 50/718 (7%) died during follow-up. Calculated creatinine clearance was 66+/-26 mL/min at 2 years. The most common adverse events were hypertension, hyperlipidemia, anemia, urinary tract infections, and diabetes. BCAR was significantly lower in subjects receiving SRL+TAC (hazard ratio [HR] 0.46, P=0.009) but not significantly lower in those receiving SRL+CsA (HR 0.62, P=0.102) compared with SRL without a calcineurin inhibitor. Graft loss or death did not significantly differ between treatment groups but were associated, respectively, with deceased donor grafts (HR 3.33, P<0.001) and increased age (HR 1.04, P<0.001). No improvement was observed in patients receiving mycophenolate mofetil in any treatment combination (HR 0.80, P=0.438 for BCAR; HR 0.93, P=0.849 for graft loss; and HR 0.75, P=0.531 for death). CONCLUSIONS.: SRL is most commonly used in combination with mycophenolate mofetil, CsA, or TAC. BCAR was least common in subjects receiving SRL+TAC, but other outcomes seemed comparable between the treatment regimens in routine practice.

Sympathetic dystrophy associated with sirolimus therapy.

The reflex sympathetic dystrophy syndrome (RSDS) in organ transplant recipients has only previously been reported in patients treated with calcineurin inhibitors. We retrospectively analyzed 393 renal transplant patients treated with sirolimus, 9 of whom developed RSDS. All the patients reported varying degrees of pain in the legs, affecting the knees, ankles, and/or feet, plus cutaneous erythema. The onset of pain ranged from 1-6 months after transplantation. At the time of diagnosis of RSDS, the mean serum creatinine was 1.4 mg/dL (range 1.0-1.7) and bone scintigraphy with 99mTc pyrophosphate showed increased uptake in all cases. The symptoms remitted 3-10 months after treatment (mean, 4 months) with calcitriol, with or without nifedipine or calcitonin, and in one case with suppression of sirolimus. We conclude that sirolimus therapy may induce RSDS in renal transplant recipients.