Purpose: Sirolimus (SRL) has been used to replace calcineurin
inhibitors (CNI) for various indications including CNI-induced toxicity.
The aim of this study was to evaluate the efficacy and safety of
switching from CNI to SRL in stable renal transplant recipients (RTR)
with low grade proteinuria (<1 g/24 h).
Methods and materials: Between 2001 and 2007, 41 patients (20
females, 21 males; mean age 47 ± 13) were switched after a median
time post-transplantation of 73.5 months (range 0.2-273.2 months).
Indications for switch were CNI nephrotoxicity (39%), thrombotic
micro-angiopathy (14.6%), post-transplantation cancer (24.4%), CNI
neurotoxicity (7.4%), or others (14.6%). Mean follow-up after SRL
switch was 23.8±16.3 months. Mean SRL dosage and through levels
were 2.4 ± 1.1 mg/day and 8 ± 2.2 ug/l respectively. Immunosuppressive
regiments were SRL + mycophenolate mofetil (MMF)
(31.7%), SRL + MMF + prednisone (36.58%), SRL + prednisone
(19.51%), SRL + Azathioprine (9.75%), or SRL alone (2.43%).
Results: Mean creatinine decreased from 164 to 143 μmol/l (p <0.03),
mean estimated glomerular filtration rate (eGFR) increased
significantly from 50.13 to 55.01 ml/minute (p <0.00001), mean
systolic and diastolic blood pressure decreased from 138 to 132 mm
Hg (p <0.03) and from 83 to78 mm Hg (p <0.01), but mean proteinuria
increased from 0.21 to 0.63 g/24 h (p <0.001). While mean total
cholesterolemia didn't increased significantly from 5.09 to 5.56
mmol/l (p = 0.06). The main complications after SRL switch were
dermatitis (19.5%), urinary tract infections (24.4%), ankle edema
(13.3%), and transient oral ulcers (20%). Acute rejection after the
switch occurred in 7.3% of patients (n = 3), and 2 acute rejections
were successfully treated with corticosteroids and 1 did not respond
to treatment (not related to switch). SRL had to be discontinued in
17% of patients (2 nephrotic syndromes, 2 severe edema, 1 acute
rejection, 1 thrombotic micro-angiopathy, and 1 fever).
Conclusion: In conclusion, we found that switching from CNI to SRL
in stable RTR was safe and associated with a significant improvement
of renal function and blood pressure. Known side-effects of SRL led
to drug discontinuation in less than 20% of patients and the acute
rejection rate was 7.3%. This experience underlines the importance of
patient selection before switching to SRL, in particular regarding preswitch
proteinuria.