Supplemental Digital Content (SDC)
Figure S1.
Baseline exposure as measured by area under the time-blood concentration curve (AUC) of cyclosporine (CsA) and mycophenolic acid (MPA) of all included patients. Mean +/- standard deviation are shown.
Supplemental Digital Content (SDC)
Figure S2.
Exposure as measured by area under the time-blood concentration curve (AUC) of mycophenolic acid (MPA) in CNI-withdrawal group. Mean and standard deviation at baseline and 6 weeks, 6 months, 1 and 3 years after withdrawal are shown.
Table S1. MDRD clearance over time according to linear mixed modelling
.MMF withdrawal CNI withdrawal p
Whole population N=79 N=79
MDRD clearance (ml/min) baseline 6 weeks
1 year 3 years
Slope (ml/min/month)
53.9+/-1.8 55.2+/-1.9 52.9+/-1.8 51.1+/-2.1 -0.096
58.0+/-1.8 63.1+/-1.9 61.1+/-1.8 59.5+/-2.1 -0.088
0.12 0.004 0.002 0.006 0.91
<50 ml/min N=33 N=30
MDRD clearance (ml/min) baseline 6 weeks 1 year 3 years Slope (ml/min/month)
39.0+/-1.3 40.9+/-1.7 38.5+/-1.7 36.7+/-2.0 -0.096
42.2+/-1.4 48.3+/-1.8 48.0+/-1.8 48.5+/-2.1 +0.008
0.10 0.004
<0.001
<0.001 0.03
≥50 ml/min N=46 N=49
MDRD clearance (ml/min) baseline 6 weeks 1 year 3 years Slope (ml/min/month)
64.7+/-1.7 65.4+/-1.9 63.2+/-1.9 61.7+/-2.6 -0.084
67.7+/-1.7 72.1+/-1.8 69.1+/-1.9 66.4+/-2.5 -0.148
0.21 0.01 0.03 0.20 0.48 Data presented as model-predicted values and standard errors of the whole population and of subpopulations with a MDRD clearance < and ≥ 50 ml/min.
MMF = mycophenolate mofetil; CNI = calcineurin inhibitor
Supplemental Digital Content (SDC)
Table S2. Rejections at 6 months.
MMF withdrawal N=79
CNI withdrawal N=79
Number (%) 1 (1.3%) 3 (3.8%)
Sex (M/F) M M
Age (yrs) 54 59; 23; 55
HLA mismatch 1-2-2 1-1-0; 0-0-0; 1-1-0
PRA (%) 4 8; 2; 0
Prior rejections no no
Previous transplantations no no
Systemic drug exposure at baseline
(CNI ng.h/ml, MPA µg.h/ml) CsA: 4142; MPA: 56 Tac: 127; MPA: 37 CsA: 2936; MPA: 55 CsA: 3664; MPA: 34 Systemic drug exposure at time of rejection
(CNI ng.h/ml, MPA µg.h/ml) CsA: 2832 MPA: 60; MPA: 68;
MPA: 61
Time post-transplantation (yrs) 1.0 2.5; 1.5; 1.5
Time after withdrawal (d) 161 75; 55; 84
Intercurrent illness no no
MMF = mycophenolate mofetil; CNI = calcineurin inhibitor; M = male; F = female; PRA= panel reactive antibodies; MPA = mycophenolic acid; CsA = cyclosporine; Tac = tacrolimus.